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1.
Nanoscale ; 11(39): 18209-18223, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31560010

RESUMO

Rheumatoid arthritis (RA) is a degenerative joint disease caused by autoimmunity; for the effective treatment of RA while avoiding the side effects of conventional drugs, we have proposed a new therapeutic strategy to eliminate the inflammatory response in RA by regulating the immune system that promotes the transformation of M1-type macrophages to M2-type macrophages. Herein, we designed and synthesized a core-shell nanocomposite (QRu-PLGA-RES-DS NPs), which showed an effective therapeutic effect on RA by accurately inducing the polarization of M2 macrophages. In this system, the quadrilateral ruthenium nanoparticles (QRuNPs) with a photothermal effect were utilized as a core and the thermosensitive molecular poly (lactic-co-glycolic acid) (PLGA) modified with the targeted molecule dextran sulfate (DS) was employed as a shell. Then, the nanocarrier QRu-PLGA-DS NPs effectively improved the water solubility and targeting of resveratrol (RES) through self-assembly. Therefore, the QRu-PLGA-RES-DS NPs significantly enhanced the ability of RES to reverse the M1 type macrophages to the M2 type macrophages through an accurate release. In vivo experiments further demonstrated that the QRu-PLGA-RES-DS NPs could effectively accumulate in the lesion area with an exogenous stimulus, and this significantly enhanced the transformation of the M2 type macrophages and decreased the recruitment of the M1 type macrophages. Furthermore, the QRu-PLGA-RES-DS NPs effectively treated RA by eliminating the inflammatory response; in addition, photoacoustic imaging (PA) of the QRu NPs provided image guidance for the distribution and analysis of nanomedicine in inflammatory tissues. Hence, this therapeutic strategy promotes the biological applications of Ru-based nanoparticles in disease treatment.


Assuntos
Hipertermia Induzida , Macrófagos/metabolismo , Nanocompostos , Fototerapia , Resveratrol , Febre Reumática/terapia , Animais , Células Endoteliais da Veia Umbilical Humana , Humanos , Macrófagos/patologia , Camundongos , Nanocompostos/química , Nanocompostos/uso terapêutico , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacocinética , Ácido Poliglicólico/farmacologia , Células RAW 264.7 , Resveratrol/farmacocinética , Resveratrol/farmacologia , Febre Reumática/metabolismo , Febre Reumática/patologia , Rutênio/química , Rutênio/farmacocinética , Rutênio/farmacologia
2.
Artif Cells Nanomed Biotechnol ; 46(sup3): S481-S491, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30299174

RESUMO

In our study, we have established a novel liquid-driven co-flow focusing (LDCF) process to fabricate curcumin (CUR)-loaded poly (lactic-co-glycolic acid) (PLGA) microparticles (CPMs). LDCF-CPMs of size 20.26 ± 2.37 µm have high encapsulation efficiency (>70%) and were intended for application in ovarian cancer by intraperitoneal (IP) administration. LDCF-CPMs have smooth surface with narrow size distribution and a core-shell structured verified by confocal microscopy which can be precisely controlled by changing the flow rates of focusing, outer and inner phases. The LDCF-CPMs reveal the physiochemical stability with sustained release profile corresponding to 95% CUR release over a period of 14 days in an in vitro release medium. Moreover, LDCF-CPMs were testified for cytotoxicity against SKOV-3 ovarian cancer cell lines and peritoneal delivery advantages by animal experiments. The pharmacokinetics of LDCF-CPMs in rats following IP injection shows slow systemic absorption with mean residence time (MRT) of 13.54 h in comparison with 9.82 and 6.74 h for SE-CPMs and free CUR, respectively. In addition, IP delivery of CUR can expose the ovarian tumour to higher concentration for a longer duration by programming the thickness of the shell. The study provides compelling evidence for LDCF-CPMs having high therapeutic opportunity in the treatment of peritoneal cancers, such as ovarian, that reside in the peritoneal cavity.


Assuntos
Antineoplásicos Fitogênicos , Curcumina , Nanopartículas , Neoplasias Ovarianas , Ácido Poliglicólico , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/farmacologia , Curcumina/química , Curcumina/farmacocinética , Curcumina/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Feminino , Humanos , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Tamanho da Partícula , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacocinética , Ácido Poliglicólico/farmacologia , Ratos , Ratos Wistar , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Acta Biomater ; 81: 208-218, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30267881

RESUMO

Targeting of CD44 isoforms containing exon v6 (CD44v6) represents a viable strategy for the therapy and/or early diagnosis of metastatic cancers of the epithelium (e.g. gastric and colorectal cancer). We developed and characterized poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) modified with polyethylene glycol (PEG) and engrafted, by site-directed conjugation, with an engineered human Fab that specifically target human CD44v6 (v6 Fab-PLGA NPs). The v6 Fab-PLGA NPs displayed spherical morphology around 300 nm and were negatively charged. They strongly bound to a CD44v6-derived peptide and, more importantly, to cells that endogenously and exogenously express CD44v6, but not to non-expressing cells and cells expressing the standard isoform of CD44. The v6 Fab-PLGA NPs also recognized CD44v6 in tumor sections from cells grown subcutaneously within mice. The NPs had nominal cytotoxicity at 50 µg/mL and withstood simulated intestinal fluid exposure. Interestingly, v6 Fab-PLGA NPs cryopreserved in 10% trehalose and stored maintained specific cell binding. In conclusion, we envision NPs targeting CD44v6 as potential in vivo diagnostic agents and/or as anti-cancer agents in patients previously stratified with CD44v6+ carcinomas. STATEMENT OF SIGNIFICANCE: The v6 Fab-PLGA NPs displayed many favorable qualities as a potential CD44v6-targeted drug and/or diagnostic delivery agent. The NPs were designed for optimal ligand orientation and for immediate administration into humans. v6 Fab-PLGA NPs strongly bound to cells that endogenously and exogenously express CD44v6, but not to non-expressing cells and cells expressing the standard isoform of CD44. Binding ability was retained after freeze-drying and long-term storage, providing evidences on the stability of Fab-functionalized NPs. These NPs can potentially be used as an in vivo diagnostic from parenteral or oral/rectal administration.


Assuntos
Citotoxinas , Portadores de Fármacos , Receptores de Hialuronatos/biossíntese , Proteínas de Neoplasias/biossíntese , Neoplasias , Ácido Poliglicólico , Linhagem Celular Tumoral , Citotoxinas/química , Citotoxinas/farmacocinética , Citotoxinas/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Humanos , Nanopartículas , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacocinética , Ácido Poliglicólico/farmacologia
4.
Int J Biol Macromol ; 118(Pt A): 932-937, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-29966670

RESUMO

In present study, HEP was successfully encapsulated into the Poly (lactic-coglycolicacid) (PLGA) to constitute the HEP-PLGA. The effects of three independent factors (the proper range of ratio of organic phase (o) to internal water phase (w1) (X1), ratio of external water phase (w2) to the primary emulsion (PE) (X2), and the concentration of PLGA (X3) on the extraction yield of encapsulation efficiency (EE) from the HEP was optimized using response surface methodology. The optimal extraction conditions for HEP-PLGA were determined as follows: X1: 8:1, X2: 7:1 and X3: 20 mg·mL-1. Under these optimal conditions, the mean experimental EE 90.86 ±â€¯0.576% was corresponded well with the predicted value of 91.81%. In addition, to investigate the transport properties of HEP and HEP-PLGA using a Caco-2 cell monolayer, and study the roles of the efflux transporters (P-gp) during the transport process. These results suggested that HEP can be absorbed more efficiently when encapsulated within the PLGA. These findings highlight the potential to the application of HEP in the formulation of functional foods. These results provide strategies in designing high absorbed polysaccharides with bioactive benefits.


Assuntos
Basidiomycota/química , Polissacarídeos Fúngicos , Ácido Láctico , Nanopartículas/química , Ácido Poliglicólico , Células CACO-2 , Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/farmacocinética , Polissacarídeos Fúngicos/farmacologia , Humanos , Ácido Láctico/química , Ácido Láctico/farmacocinética , Ácido Láctico/farmacologia , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacocinética , Ácido Poliglicólico/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico
5.
Int J Pharm ; 547(1-2): 10-23, 2018 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-29751140

RESUMO

Resistance to antiepileptic drugs (AEDs) is a major clinical problem. The overexpression of P-glycoprotein (Pgp), one of the main transporters limiting the entry of xenobiotics into the brain, is among the factors contributing to the AED resistance. Presently, there is no consensus on the interaction of carbamazepine (CBZ) with the Pgp. This study investigates the effect of the Pgp inhibitor verapamil on the anticonvulsant effect of CBZ and its nanoparticulate formulation in the rat model of isoniazid-induced epilepsy. Verapamil significantly increased the anticonvulsant effect of CBZ and reduced its effective dose by at least 30% (from 30 mg/kg to 20 mg/kg). Binding of carbamazepine to the poloxamer 188-coated PLGA nanoparticles enabled a 30-fold increase of its anticonvulsive effect, as compared to the free drug. The inhibition of Pgp did not influence the effectivity of carbamazepine encapsulated in nanoparticles.


Assuntos
Anticonvulsivantes/administração & dosagem , Carbamazepina/administração & dosagem , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Nanopartículas/administração & dosagem , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Animais , Anticonvulsivantes/química , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/uso terapêutico , Encéfalo/fisiopatologia , Carbamazepina/química , Carbamazepina/farmacocinética , Carbamazepina/uso terapêutico , Relação Dose-Resposta a Droga , Sistemas de Liberação de Medicamentos , Epilepsia Resistente a Medicamentos/induzido quimicamente , Epilepsia Resistente a Medicamentos/fisiopatologia , Eletrocorticografia , Isoniazida , Ácido Láctico/administração & dosagem , Ácido Láctico/química , Ácido Láctico/farmacocinética , Ácido Láctico/uso terapêutico , Masculino , Nanopartículas/química , Nanopartículas/uso terapêutico , Poloxâmero/administração & dosagem , Poloxâmero/química , Poloxâmero/farmacocinética , Poloxâmero/uso terapêutico , Ácido Poliglicólico/administração & dosagem , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacocinética , Ácido Poliglicólico/uso terapêutico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos Wistar , Verapamil/farmacologia
6.
Int J Biol Macromol ; 116: 648-663, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29723623

RESUMO

PURPOSE: Enhancing the ocular hypotensive effect of forskolin (FK) by means of biodegradable chitosan (CS) coated poly lactic-co-glycolic acid (PLGA) nanoparticles (NP's). METHODS: One step emulsion-sonication process was employed for the formulation of CS-PLGA NP's with optimization being carried out by employing a four factor four level Box Behnken Design. The physical and spectral characterization, drug release, permeation, confocal and ocular tolerance studies (ex-vivo &in vivo) were performed. The corneal retention was assessed by gamma scintigraphic analysis and dexamethasone induced glaucamotous rabbit's intraocular pressure (IOP) was measured by means of Schiotz tonometer. RESULTS AND DISCUSSION: Particle size of optimized CS-PLGA NP's was found as 201.56 ±â€¯10.92 nm with a good PDI and positive zeta potential value. Entrapment efficiency and drug loading were found to be 72.32 ±â€¯1.12% and 28.39 ±â€¯1.67% respectively. Spectral characterization confirmed the purity and encapsulation of the drug within polymeric system. Sustained drug release and enhanced permeation profile was observed with maximum depth penetration. Ocular tolerance studies explicated its safe use. Scintigraphy studies indicated longer retention of CS-PLGA NP's while increased effectiveness after single instillation in reducing the intraocular pressure was observed. CONCLUSION: CS-PLGA-NP's could be successfully formulated and are an excellent vehicle for FK in ocular delivery.


Assuntos
Quitosana , Colforsina/efeitos adversos , Córnea/metabolismo , Dexametasona , Portadores de Fármacos , Ácido Láctico , Nanopartículas , Hipotensão Ocular , Ácido Poliglicólico , Animais , Linhagem Celular , Quitosana/química , Quitosana/farmacocinética , Quitosana/farmacologia , Colforsina/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Dexametasona/química , Dexametasona/farmacocinética , Dexametasona/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Cabras , Ácido Láctico/química , Ácido Láctico/farmacocinética , Ácido Láctico/farmacologia , Nanopartículas/química , Nanopartículas/uso terapêutico , Hipotensão Ocular/induzido quimicamente , Hipotensão Ocular/tratamento farmacológico , Hipotensão Ocular/metabolismo , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacocinética , Ácido Poliglicólico/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Coelhos
7.
Drug Des Devel Ther ; 12: 711-719, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29670329

RESUMO

Background: Norquetiapine (N-desalkyl quetiapine, NQ) is an active metabolite of quetiapine with stable pharmacokinetic and pharmacological properties. However, its short half-life is a drawback for clinical applications, and long-acting formulations are required. Purpose: The objectives of this study were to prepare improved entrapment efficiency NQ freebase microspheres by the solvent evaporation method with poly(d,l-lactic-co-glycolic acid) (PLGA) as a release modulator and to evaluate their physicochemical and in vitro/in vivo release properties. Methods: NQ freebase PLGA (1:5 w/w) formulations were prepared by the oil-in-water (o/w) emulsion-solvent evaporation method. A solution of the drug and PLGA in 9:1 v/v dichloromethane:ethanol was mixed with 0.2% polyvinyl alcohol and homogenized at 2,800 rpm. The emulsion was stirred for 3 h to dilute and evaporate the solvent. After that, the resulting product was freeze-dried. Drug-loading capacity was measured by the validated RP-HPLC method. The surface morphology of the microspheres was observed by scanning electron microscopy (SEM), and the physicochemical properties were evaluated by differential scanning calorimetry, powder X-ray diffraction, and Fourier-transform infrared spectroscopy particle size distribution. The in vitro dissolution test was performed using a rotary shaking bath at 37°C, with constant shaking at 50 rpm in sink condition. Results: The NQ freebase microspheres prepared by o/w emulsion-solvent evaporation showed over 30% efficiency. NQ was confirmed to be amorphous in the microspheres by powder X-ray diffraction and differential scanning calorimetry. Special chemical interaction in the microspheres was not observed by FT-IR. The in vitro dissolution test demonstrated that the prepared microspheres' release properties were maintained for more than 20 days. The in vivo test also confirmed that the particles' long acting properties were maintained. Therefore, good in vitro-in vivo correlation was established. Conclusion: In this study, NQ freebase-PLGA microspheres showed potential for the treatment of schizophrenia for long-periods.


Assuntos
Dibenzotiazepinas/farmacocinética , Ácido Láctico/farmacocinética , Microesferas , Ácido Poliglicólico/farmacocinética , Animais , Dibenzotiazepinas/administração & dosagem , Dibenzotiazepinas/química , Ácido Láctico/administração & dosagem , Ácido Láctico/química , Tamanho da Partícula , Ácido Poliglicólico/administração & dosagem , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos , Ratos Sprague-Dawley , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície
8.
Eur J Pharm Sci ; 118: 24-31, 2018 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-29555501

RESUMO

For patient convenience, sustained release Adefovir Poly-d,l-lactic-co-glycolic acid (PLGA) microspheres were formulated to relieve the daily use of the drug which is a problem for patients treated from chronic hepatitis-B. PLGA microspheres were prepared and characterized by entrapment efficiency, particle size distribution and scanning electron microscopy (SEM). In-vitro release and in-vivo studies were carried out. Factors such as drug: polymer ratio, polymer viscosity and polymer lactide content were found to be important variables for the preparation of PLGA Adefovir microspheres. Fourier transform infrared (FTIR) analysis and differential scanning calorimetry (DSC) were performed to determine any drug-polymer interactions. One way analysis of variance (ANOVA) was employed to analyze the pharmacokinetic parameters after intramuscular injection of the pure drug and the selected PLGA microspheres into rats. FTIR and DSC revealed a significant interaction between the drug and the polymer. Reports of SEM before and after 1 and 24 h release showed that the microspheres had nonporous smooth surface even after 24 h release. The entrapment efficiency ranged between 55.83 and 86.95% and in-vitro release studies were continued for 16, 31 and 90 days. The pharmacokinetic parameters and statistical analysis showed a significant increase in the Tmax, AUC0-t and MRT, and a significant decrease in the Cmax of the tested formulation (p < 0.05). Results demonstrated that PLGA Adefovir microspheres could be used for long-term treatment of chronic hepatitis-B instead of the daily dose used by the patient.


Assuntos
Adenina/análogos & derivados , Antivirais/administração & dosagem , Sistemas de Liberação de Medicamentos , Ácido Láctico/administração & dosagem , Microesferas , Organofosfonatos/administração & dosagem , Ácido Poliglicólico/administração & dosagem , Adenina/administração & dosagem , Adenina/sangue , Adenina/química , Adenina/farmacocinética , Animais , Antivirais/sangue , Antivirais/química , Antivirais/farmacocinética , Liberação Controlada de Fármacos , Hepatite B Crônica/tratamento farmacológico , Ácido Láctico/química , Ácido Láctico/farmacocinética , Masculino , Organofosfonatos/sangue , Organofosfonatos/química , Organofosfonatos/farmacocinética , Tamanho da Partícula , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacocinética , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos
9.
Int J Pharm ; 542(1-2): 47-55, 2018 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-29501738

RESUMO

Oral administration of insulin increases patient comfort and could improve glycemic control thanks to the hepatic first passage. However, challenges remain. The current approach uses poly (d, lactic-co-glycolic) acid (PLGA) nanoparticles (NPs), an effective drug carrier system with a long acting profile. However, this system presents a bioavailability of less than 20% for insulin encapsulation. In this context, physico-chemical parameters like surface charge could play a critical role in NP uptake by the intestinal barrier. Therefore, we developed a simple method to modulate NP surface charge to test its impact on uptake in vitro and finally on NP efficiency in vivo. Various NPs were prepared in the presence (+) or absence (-) of polyvinyl alcohol (PVA), sodium dodecyl sulfate (SDS), and/or coated with chitosan chloride. In vitro internalization was tested using epithelial culture of Caco-2 or using a co-culture (Caco-2/RevHT29MTX) by flow cytometry. NPs were then administered by oral route using a pharmaceutical complex vector (100 or 250 UI/kg) in a diabetic rat model. SDS-NPs (-42 ±â€¯2 mV) were more negatively charged than -PVA-NPs (-22 ±â€¯1 mV) and chitosan-coated NPs were highly positively charged (56 ±â€¯2 mV) compared to +PVA particles (-2 ±â€¯1 mV), which were uncharged. In the Caco-2 model, NP internalization was significantly improved by using negatively charged NPs (SDS NPs) compared to using classical NPs (+PVA NPs) and chitosan-coated NPs. Finally, the efficacy of insulin SDS-NPs was demonstrated in vivo (100 or 250 UI insulin/kg) with a reduction of blood glucose levels in diabetic rats. Formulation of negatively charged NPs represents a promising approach to improve NP uptake and insulin bioavailability for oral delivery.


Assuntos
Portadores de Fármacos/administração & dosagem , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Nanopartículas/administração & dosagem , Dodecilsulfato de Sódio/administração & dosagem , Animais , Disponibilidade Biológica , Glicemia/análise , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Cocultura , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/uso terapêutico , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/uso terapêutico , Insulina/química , Insulina/farmacocinética , Insulina/uso terapêutico , Ácido Láctico/administração & dosagem , Ácido Láctico/química , Ácido Láctico/farmacocinética , Ácido Láctico/uso terapêutico , Masculino , Nanopartículas/química , Nanopartículas/uso terapêutico , Ácido Poliglicólico/administração & dosagem , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacocinética , Ácido Poliglicólico/uso terapêutico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos Wistar , Dodecilsulfato de Sódio/química , Dodecilsulfato de Sódio/farmacocinética , Dodecilsulfato de Sódio/uso terapêutico , Propriedades de Superfície
10.
Drug Deliv Transl Res ; 8(2): 329-341, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28417445

RESUMO

Curcumin has shown promising inhibitory activity against HER-2-positive tumor cells in vitro but suffers from poor oral bioavailability in vivo. Our lab has previously developed a polymeric microparticle formulation for sustained delivery of curcumin for chemoprevention. The goal of this study was to examine the anticancer efficacy of curcumin-loaded polymeric microparticles in a transgenic mouse model of HER-2 cancer, Balb-neuT. Microparticles were injected monthly, and mice were examined for tumor appearance and growth. Initiating curcumin microparticle treatment at 2 or 4 weeks of age delayed tumor appearance by 2-3 weeks compared to that in control mice that received empty microparticles. At 12 weeks, abnormal (lobular hyperplasia, carcinoma in situ, and invasive carcinoma) mammary tissue area was significantly decreased in curcumin microparticle-treated mice, as was CD-31 staining. Curcumin treatment decreased mammary VEGF levels significantly, which likely contributed to slower tumor formation. When compared to saline controls, however, blank microparticles accelerated tumorigenesis and curcumin treatment abrogated this effect, suggesting that PLGA microparticles enhance tumorigenesis in this model. PLGA microparticle administration was shown to be associated with higher plasma lactic acid levels and increased activation of NF-κΒ. The unexpected side effects of PLGA microparticles may be related to the high dose of the microparticles that was needed to achieve sustained curcumin levels in vivo. Approaches that can decrease the overall dose of curcumin (for example, by increasing its potency or reducing its clearance rate) may allow the development of sustained release curcumin dosage forms as a practical approach to cancer chemoprevention.


Assuntos
Anticarcinógenos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Curcumina/administração & dosagem , Portadores de Fármacos/administração & dosagem , Ácido Láctico/administração & dosagem , Ácido Poliglicólico/administração & dosagem , Animais , Anticarcinógenos/farmacocinética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Curcumina/farmacocinética , Citocinas/sangue , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/farmacocinética , Modelos Animais de Doenças , Portadores de Fármacos/farmacocinética , Feminino , Genes erbB-2 , Ácido Láctico/sangue , Ácido Láctico/farmacocinética , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , NF-kappa B/metabolismo , Neovascularização Patológica/tratamento farmacológico , Ácido Poliglicólico/farmacocinética , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Fator A de Crescimento do Endotélio Vascular/metabolismo
11.
Artif Cells Nanomed Biotechnol ; 46(2): 432-446, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28503995

RESUMO

Docetaxel (DTX), a cytotoxic taxane, is a poor water-soluble drug and exhibits less oral bioavailability. Current research investigates the effective transport, for DTX-loaded chitosan (CS)-coated-poly-lactide-co-glycolide (PLGA)-nanoparticles (NPs) (DTX-CS-PLGA-NPs) and DTX-PLGA-NPs as well as a novel third-generation P-gp inhibitor i.e. GF120918 (Elacridar), across intestinal epithelium with its successive uptake by the tumour cells in an in vitro model. The prepared NPs showed a spherical shape particle size i.e. <123.96 nm with polydispersity index (PDI) of <0.290 whereas for CS-coated NPs, the zeta potential was converted from negative to positive value along with a small modification in particle size distribution. The entrapment efficiency observed for DTX-CS-PLGA-NPs was 74.77%, whereas the in vitro release profile revealed an initial rapid DTX release followed by a sustained release pattern. For apparent permeability, DTX-CS-PLGA-NPs and DTX-PLGA-NPs along with GF120918 showed a five-fold (p < .01) and 2.2-fold enhancement, respectively, as observed in rat ileum permeation study. Similarly, for pharmacokinetic (PK) studies, higher oral bioavailability was observed from DTX-CS-PLGA-NPs (5.11-folds) and DTX-PLGA-NPs (3.29-folds) as compared with DTX-suspension (DTX-S). Cell uptake studies on A549 cells as performed for DTX-CS-PLGA-NPs and DTX-PLGA-NPs loaded with rhodamine 123 dye, exhibited enhanced uptake as compared with plain dye solution. The enhanced uptake for DTX-CS-PLGA-NPs and DTX-PLGA-NPs formulations in the presence of GF120918 was confirmed further with the help of confocal laser scanning microscopic images (CLSM). The potential of the third-generation novel P-gp inhibitor (GF120918) investigated for the effective delivery of DTX as well as investigation of permeability and uptake studies whereby a strong potential of GF120918 for effective oral delivery was established.


Assuntos
Portadores de Fármacos/química , Neoplasias Intestinais/tratamento farmacológico , Ácido Láctico/química , Terapia de Alvo Molecular , Nanopartículas/química , Ácido Poliglicólico/química , Taxoides/química , Células A549 , Animais , Transporte Biológico , Docetaxel , Portadores de Fármacos/metabolismo , Portadores de Fármacos/farmacocinética , Liberação Controlada de Fármacos , Humanos , Ácido Láctico/metabolismo , Ácido Láctico/farmacocinética , Permeabilidade , Ácido Poliglicólico/metabolismo , Ácido Poliglicólico/farmacocinética , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos , Propriedades de Superfície , Taxoides/uso terapêutico , Distribuição Tecidual
12.
J Biomed Mater Res B Appl Biomater ; 106(1): 201-208, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28067984

RESUMO

This study evaluated the sustained release effect of clarithromycin-loaded in PLGA microspheres in a rabbit calvaria defect model. Four bone defects (ø5.0) were created in the calvaria of New Zealand White rabbits (n = 21, n = 7/time point). The defects were randomly designated to four groups. Group 1: No augmentation (sham), Group 2: beta-tricalcium phosphate (ß-TCP), Group 3: ß-TCP with 0.12 µg clarithromycin, and Group 4: ß-TCP with 6.12 µg PLGA microspheres loaded with 0.12 µg Clarithromycin. After 2, 4, and 12 weeks of healing, bone regeneration was evaluated using micro-computed tomography (µCT) and histology. Clarithromycin release from PLGA microspheres revealed sustained release for around 4 weeks with ∼50% release during the first week. Histologically, new bone formation was evident at 2 and 4 weeks of healing in all groups and bone formation increased as a function of healing time. At 12 weeks, Group 4 showed significantly higher amount of newly formed bone compared to Group 1. The µCT showed that Group 4 expressed significantly higher bone formation compared to Group 1 at all time points. The in vivo findings showed that ß-TCP with clarithromycin-loaded microspheres can enhance bone formation in bone defects. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 201-208, 2018.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Claritromicina , Ácido Láctico , Microesferas , Ácido Poliglicólico , Crânio , Animais , Claritromicina/química , Claritromicina/farmacocinética , Claritromicina/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Ácido Láctico/química , Ácido Láctico/farmacocinética , Ácido Láctico/farmacologia , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacocinética , Ácido Poliglicólico/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Coelhos , Crânio/lesões , Crânio/metabolismo , Crânio/patologia
13.
J Control Release ; 268: 407-415, 2017 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-29111150

RESUMO

For polymeric nanoparticles (NPs) to deliver more drugs to tumors than free drug solution, it is critical that the NPs establish interactions with tumor cells and avoid removal from the tumors. Since traditional polyethylene glycol (PEG) surface layer interferes with the cell-NP interaction in tumors, we used a water-soluble and blood-compatible chitosan derivative called zwitterionic chitosan (ZWC) as an alternative surface coating for poly(lactic-co-glycolic acid) (PLGA) NPs. The ZWC-coated PLGA NPs showed pH-dependent surface charge profiles and differential cellular interactions according to the pH of the medium. The in vivo delivery of ZWC-coated NPs was evaluated in mice bearing LS174T-xenografts using magnetic resonance (MR) imaging and fluorescence whole body imaging, which respectively tracked iron oxide particles and indocyanine green (ICG) encapsulated in the NPs as tracers. MR imaging showed that ZWC-coated NPs were more persistent in tumors than PEG-coated NPs, in agreement with the in vitro results. However, the fluorescence imaging indicated that the increased NP retention in tumors by the ZWC coating did not significantly affect the ICG distribution in tumors due to the rapid release of the dye. This study shows that stable drug retention in NPs during circulation is a critical prerequisite to successful translation of the potential benefits of surface-engineered NPs.


Assuntos
Quitosana/administração & dosagem , Portadores de Fármacos/administração & dosagem , Ácido Láctico/administração & dosagem , Nanopartículas/administração & dosagem , Ácido Poliglicólico/administração & dosagem , Animais , Linhagem Celular Tumoral , Quitosana/química , Quitosana/farmacocinética , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Feminino , Humanos , Ácido Láctico/química , Ácido Láctico/farmacocinética , Imagem por Ressonância Magnética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Neoplasias/metabolismo , Imagem Óptica , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacocinética , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Imagem Corporal Total
14.
Int J Pharm ; 532(1): 55-65, 2017 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-28870763

RESUMO

The properties of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and penetration enhancers play a deciding role in the inner ear drug delivery of NPs across the round window membrane (RWM). Thus, PLGA nano-based systems with a variety of particle sizes and surface chemistries and those combined with cell-penetrating peptides (CPPs) as penetration enhancers were devised to explore their impact on the cochlear drug delivery in vivo. First, we demonstrated that the properties of NPs dictated the extent of NP cochlear entry by near-infrared fluorescence imaging. NPs with the sizes of 150 and 300nm had faster entry than that of 80nm NPs. At 0.5h, among the NPs unmodified and modified with chitosan (CS), poloxamer 407 (P407) and methoxy polyethylene glycol, CS-PLGA-NPs (positive surface charge) carried payload to the cochlea fastest, whereas P407-PLGA-NPs (surface hydrophilicity) showed the greatest distribution in the cochlea at 24h. Compared to other CPPs (TAT, penetratin and poly(arginine)8), low molecular weight protamine (LMWP) performed an outstanding enhanced NP cellular uptake in HEI-OC1 cells and cochlear entry. More importantly, NPs with optimized properties and CPPs may be combined to improve RWM penetration. For the first time, we confirmed that the combination of P407-PLGA-NPs (mean diameter: 100-200nm) and LMWP provided a synergistic enhancement in NP entry to the organ of Corti and stria vascularis without inducing pathological alteration of cochlear tissues and RWM. Taken together, we propose an effective PLGA nano-based strategy for enhanced drug delivery to the inner ear tissues that combines hydrophilic molecule-modified NPs and CPPs, ultimately opening an avenue for superior inner ear therapy.


Assuntos
Peptídeos Penetradores de Células/administração & dosagem , Cóclea/metabolismo , Sistemas de Liberação de Medicamentos , Ácido Láctico/administração & dosagem , Nanopartículas/administração & dosagem , Poloxâmero/administração & dosagem , Ácido Poliglicólico/administração & dosagem , Animais , Linhagem Celular , Peptídeos Penetradores de Células/farmacocinética , Cobaias , Ácido Láctico/farmacocinética , Camundongos , Poloxâmero/farmacocinética , Ácido Poliglicólico/farmacocinética , Copolímero de Ácido Poliláctico e Ácido Poliglicólico
15.
Acta Biomater ; 64: 279-289, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28951330

RESUMO

Site-specific controlled release of exogenous angiogenic growth factors, such as recombinant human basic fibroblast growth factor (rhbFGF), has become a promising approach to improve peripheral vascular disease. Here, we have developed an implant composed of spiral magnesium (Mg) and a coating made using poly(lactic-co-glycolic acid) (PLGA) with encapsulated rhbFGF (Mg-PLGA-rhbFGF). The encapsulated protein could release continually for 4weeks with well preserved bioactivity. We compared the angiogenic effect produced by Mg-PLGA-rhbFGF with that of a PLGA implant loaded with rhbFGF (PLGA-rhbFGF). The incorporation of Mg in the implant raised the microclimate pH in the polymer, which preserved the stability of rhbFGF. Mg-PLGA-rhbFGF exhibited advantages over PLGA-rhbFGF implant in terms of a cytocompatibility evaluation. An in vivo angiogenesis test further confirmed the efficacy of released rhbFGF. HE, CD31 and α-SMA staining revealed that the controlled release of rhbFGF from the Mg-PLGA-rhbFGF implant was superior in promoting angiogenesis compared with that of the PLGA-rhbFGF implant. Four weeks post-implantation, the capillary density of the Mg-PLGA-rhbFGF group was significantly higher than that of the PLGA-rhbFGF, control and the normal group (p<0.05, p<0.01 and p<0.01, respectively). Furthermore, the limb blood perfusion ratios of the Mg-PLGA-rhbFGF and PLGA-rhbFGF groups were dramatically increased, at 99.1±2.9% and 80.7±3.2%, respectively, whereas the ischemic limb did not recover in the control group. The biocompatibility of the implants was also evaluated. In conclusion, Mg-PLGA-based, sustained local delivery of rhbFGF promotes post-ischemic angiogenesis and blood flow recovery. The results suggest potential therapeutic usefulness of Mg-PLGA-rhbFGF for tissue ischemia. STATEMENT OF SIGNIFICANCE: Magnesium (Mg)-based implant has been already used in patients with critical limb ischemia. Site-specific controlled release of recombinant human basic fibroblast growth factor (rhbFGF), has become a promising approach to improve peripheral vascular disease. We report here on a novel combination implant composed of spiral magnesium and a coating made using poly(lactic-co-glycolic acid) (PLGA) with encapsulated rhbFGF (Mg-PLGA-rhbFGF). The preparation method does not involve any complex processes and results in a high encapsulation efficiency (approximately 100%). The degradation of metal Mg raise the microclimate pH in the PLGA polymer, which could well preserve the bioactivity of rhbFGF incorporated in the implant. Mg-PLGA-based, sustained local delivery of rhbFGF promotes post-ischemic angiogenesis and blood flow recovery in rat limb ischemic model. This work marks the first report for controlled release of rhbFGF in combination with metal Mg, and suggests potential therapeutic usefulness of Mg-PLGA-rhbFGF for tissue ischemia.


Assuntos
Plásticos Biodegradáveis , Fator 2 de Crescimento de Fibroblastos , Membro Posterior/irrigação sanguínea , Isquemia/tratamento farmacológico , Ácido Láctico , Magnésio , Ácido Poliglicólico , Animais , Plásticos Biodegradáveis/química , Plásticos Biodegradáveis/farmacocinética , Plásticos Biodegradáveis/farmacologia , Modelos Animais de Doenças , Implantes de Medicamento , Fator 2 de Crescimento de Fibroblastos/química , Fator 2 de Crescimento de Fibroblastos/farmacocinética , Fator 2 de Crescimento de Fibroblastos/farmacologia , Humanos , Ácido Láctico/química , Ácido Láctico/farmacocinética , Ácido Láctico/farmacologia , Magnésio/química , Magnésio/farmacocinética , Magnésio/farmacologia , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacocinética , Ácido Poliglicólico/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos
16.
Adv Healthc Mater ; 6(23)2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28841776

RESUMO

Glioma is among the most formidable brain cancers due to location in the brain. Cholera toxin subunit B (CTB) is investigated to facilitate multifunctional glioma-targeted drug delivery by targeting the glycosphingolipid GM1 expressed in the blood-brain barrier (BBB), neovasulature, and glioma cells. When modified on the surface of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (CTB-NPs), CTB fully retains its bioactivity after 24 h incubation in the fresh mouse plasma. The formed protein corona (PC) of CTB-NP and plain PLGA nanoparticles (NP) after incubation in plasma is analyzed using liquid chromatography tandem massspectrometry (nano-LC-MS/MS). CTB modification does not alter the protein components of the formed PC, macrophage phagocytosis, or pharmacokinetic profiles. CTB-NP can efficiently penetrate the in vitro BBB model and target glioma cells and human umbilical vascular endothelial cells. Paclitaxel is loaded in NP (NP/PTX) and CTB-NP (CTB-NP/PTX), and their antiglioma effects are assessed in nude mice bearing intracranial glioma. CTB-NP/PTX can efficiently induce apoptosis of intracranial glioma cells and ablate neovasulature in vivo, resulting in significant prolongation of survival of nude mice bearing intracranial glioma (34 d) in comparison to those treated with NP/PTX (29 d), Taxol (24 d), and saline (21 d). The present study suggests a potential multifunctional glioma-targeted drug delivery system enabled by cholera toxin subunit B.


Assuntos
Toxina da Cólera , Sistemas de Liberação de Medicamentos/métodos , Glioma/tratamento farmacológico , Nanopartículas , Paclitaxel , Animais , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Linhagem Celular Tumoral , Toxina da Cólera/química , Toxina da Cólera/farmacocinética , Toxina da Cólera/farmacologia , Glioma/metabolismo , Glioma/patologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Ácido Láctico/química , Ácido Láctico/farmacocinética , Ácido Láctico/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Nanopartículas/uso terapêutico , Paclitaxel/química , Paclitaxel/farmacocinética , Paclitaxel/farmacologia , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacocinética , Ácido Poliglicólico/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Células RAW 264.7 , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Acta Biomater ; 59: 181-191, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28688985

RESUMO

Most photothermal converting systems are not biodegradable, which bring the uneasiness when they are administered into human body due to the uncertainty of their fate. Hereby, we developed a mussel-inspired PLGA/polydopamine core-shell nanoparticle for cancer photothermal and chemotherapy. With the help of an anti-EGFR antibody, the nanoparticle could effectively enter head and neck cancer cells and convert near-infrared light to heat to trigger drug release from PLGA core for chemotherapy as well as ablate tumors by the elevated temperature. Due to the unique nanoparticle concentration dependent peak working-temperature nature, an overheating or overburn situation can be easily prevented. Since the nanoparticle was retained in the tumor tissue and subsequently released its payload inside the cancer cells, no any doxorubicin-associated side effects were detected. Thus, the developed mussel-inspired PLGA/polydopamine core-shell nanoparticle could be a safe and effective tool for the treatment of head and neck cancer. STATEMENT OF SIGNIFICANCE: The described EGFR targeted PLGA/polydopamine core-shell nanoparticle (PLGA/PD NP) is novel in the following aspects: Different from most photothermal converting nanomaterials, PLGA/PD NP is biodegradable, which eliminates the long-term safety concerns thwarting the clinical application of photothermal therapy. Different from most photothermal nanomaterials, upon NIR irradiation, PLGA/PD NP quickly heats its surrounding environment to a NP concentration dependent peak working temperature and uniquely keeps that temperature constant through the duration of light irradiation. Due to this unique property an overheating or overburn situation for the adjacent healthy tissue can be easily avoided. The PLGA/PD NP releases its payload through detaching PD shell under NIR laser irradiation. The EGFR-targeted doxorubicin-loaded PLGA/PD NP effectively eradicate head and neck tumor in vivo through the synergism of photothermal therapy and chemotherapy while not introducing doxorubicin associated cardiotoxicity.


Assuntos
Doxorrubicina , Sistemas de Liberação de Medicamentos/métodos , Neoplasias de Cabeça e Pescoço/terapia , Hipertermia Induzida/métodos , Indóis , Ácido Láctico , Nanopartículas , Fototerapia/métodos , Ácido Poliglicólico , Polímeros , Animais , Bivalves , Linhagem Celular Tumoral , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Receptores ErbB/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Indóis/química , Indóis/farmacocinética , Indóis/farmacologia , Raios Infravermelhos , Ácido Láctico/química , Ácido Láctico/farmacocinética , Ácido Láctico/farmacologia , Nanopartículas/química , Nanopartículas/uso terapêutico , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacocinética , Ácido Poliglicólico/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Polímeros/química , Polímeros/farmacocinética , Polímeros/farmacologia
18.
J Control Release ; 262: 18-27, 2017 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-28700900

RESUMO

Pharmacological therapies for cardiovascular diseases are limited by short-term pharmacokinetics and extra-cardiac adverse effects. Improving delivery selectivity specifically to the heart, wherein therapeutic drug levels can be maintained over time, is highly desirable. Nanoparticle (NP)-based pericardial drug delivery could provide a strategy to concentrate therapeutics within a unique, cardiac-restricted compartment to allow sustained drug penetration into the myocardium. Our objective was to explore the kinetics of myocardial penetration and retention after pericardial NP drug delivery. Fluorescently-tagged poly(lactic-co-glycolic acid) (PLGA) NPs were loaded with BODIPY, a fluorophore, and percutaneously administered into the pericardium via subxiphoid puncture in rabbits. At distinct timepoints hearts were examined for presence of NPs and BODIPY. PLGA NPs were found non-uniformly distributed on the epicardium following pericardial administration, displaying a half-life of ~2.5days in the heart. While NPs were mostly confined to epicardial layers, BODIPY was capable of penetrating into the myocardium, resulting in a transmural gradient. The distinct architecture and physiology of the different regions of the heart influenced BODIPY distribution, with fluorophore penetrating more readily into atria than ventricles. BODIPY proved to have a long-term presence within the heart, with a half-life of ~7days. Our findings demonstrate the potential of utilizing the pericardial space as a sustained drug-eluting reservoir through the application of nanoparticle-based drug delivery, opening several exciting avenues for selective and prolonged cardiac therapeutics.


Assuntos
Ácido Láctico/administração & dosagem , Miocárdio/metabolismo , Nanopartículas/administração & dosagem , Ácido Poliglicólico/administração & dosagem , Animais , Compostos de Boro/administração & dosagem , Compostos de Boro/farmacocinética , Vias de Administração de Medicamentos , Feminino , Corantes Fluorescentes/administração & dosagem , Corantes Fluorescentes/farmacocinética , Ácido Láctico/farmacocinética , Ácido Poliglicólico/farmacocinética , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Coelhos
19.
Acta Biomater ; 60: 244-255, 2017 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-28713015

RESUMO

In this study, we developed a folate (FA)-conjugated and pH-responsive active targeting micellar system for anti-cancer drug delivery. In this system, FA was attached to the terminal of the hydrophilic segment of poly(lactic acid)-poly(L-lysine) (PLA-PLL), and PLL was modified by a citric acid group. The FA receptor-mediated active targeting and electrostatic interaction between micelles and cell membrane due to a negative-to-positive charge reversal was combined in one micellar anti-cancer drug delivery system to enhance the tumour targeting and cellular internalisation of micelles. In vitro and in vivo anti-cancer studies demonstrated that the doxorubicin-loaded, FA-conjugated and pH-responsive polymeric micelles possess an enhanced and effective cancer efficiency. STATEMENT OF SIGNIFICANCE: Negatively charged nano-carriers prolonged anti-cancer drugs' blood circulation. However it is difficult to be internalised. Therefore, a negative-to-positive charged micelle surface could improve selectivity for tumour cells and increase uptake chance. In this study, we developed a folate (FA)-conjugated and pH-responsive active targeting micellar system for anti-cancer drug delivery. The FA receptor-mediated active targeting and electrostatic interaction between micelles and cell membrane due to a negative-to-positive charge reversal was combined in one micellar anti-cancer drug delivery system to enhance the tumour targeting and cellular internalisation of micelles. In vitro and in vivo anti-cancer studies demonstrated that the doxorubicin-loaded, FA-conjugated and pH-responsive polymeric micelles possess an enhanced and effective cancer efficiency.


Assuntos
Doxorrubicina , Ácido Láctico , Micelas , Neoplasias Experimentais/tratamento farmacológico , Ácido Poliglicólico , Células A549 , Animais , Ácido Cítrico/química , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Células HeLa , Células Hep G2 , Humanos , Concentração de Íons de Hidrogênio , Ácido Láctico/química , Ácido Láctico/farmacocinética , Ácido Láctico/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacocinética , Ácido Poliglicólico/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Ann Biomed Eng ; 45(10): 2348-2359, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28653294

RESUMO

While delayed delivery of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with improved tendon healing, early delivery has been associated with impaired healing. Therefore, NSAID use is appropriate only if the dose, timing, and mode of delivery relieves pain but does not impede tissue repair. Because delivery parameters can be controlled using drug-eluting nanofibrous scaffolds, our objective was to develop a scaffold for local controlled release of ibuprofen (IBP), and characterize the release profile and degradation both in vitro and in vivo. We found that when incubated in vitro in saline, scaffolds containing IBP had a linear release profile. However, when implanted subcutaneously in vivo or when incubated in vitro in serum, scaffolds showed a rapid burst release. These data demonstrate that scaffold properties are dependent on the environment in which they are placed and the importance of using serum, rather than saline, for initial in vitro evaluation of biofactor release from biodegradable scaffolds.


Assuntos
Ácido Láctico , Nanofibras , Ácido Poliglicólico , Animais , Implantes de Medicamento , Ibuprofeno/química , Ibuprofeno/farmacocinética , Ibuprofeno/farmacologia , Ácido Láctico/química , Ácido Láctico/farmacocinética , Ácido Láctico/farmacologia , Nanofibras/química , Nanofibras/uso terapêutico , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacocinética , Ácido Poliglicólico/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos , Ratos Sprague-Dawley
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