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1.
Head Face Med ; 15(1): 27, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31711509

RESUMO

BACKGROUND: Controlled release of proteins bound to conventional bone substitutes is still insufficient. Therefore, this study evaluates in-vitro release kinetics of the model protein FITC-BSA (fluorescein conjugated bovine serum albumine) from insoluble bovine collagenous bone matrices (ICBM) with different polymer coatings. Analyzes aim at comparing FITC-BSA release from uncoated versus coated ICBM over time to find bone substitute coatings with consistent release profiles. METHODS: Release kinetics of FITC-BSA from uncoated as well as coated ICBM with five different polymers (RESOMER R 203 H, RG 503 H, RG 504 H, RG 505, L 206 S) were measured over a period of 11 days (d). Measurements were conducted after 6 h (h), 12 h, 24 h, 3 d, 5 d, 7 d, 9 d and 11 d with six samples for each coated ICBM. Two groups were formed (1) with and (2) without medium change at times of measurement. For each group ANOVA with post-hoc Bonferroni testing was used. Scanning electron microscopy assessed morphologic differences between ICBM coating. RESULTS: In group 1 approx. 70% of FITC-BSA release from uncoated ICBM occurred after 6 h compared to approx. 50% in group 2. Only polymers with medium inherent viscosity, i.e. RESOMER RG 503 H, constantly showed significantly more FITC-BSA release throughout 11 d than uncoated ICBM (p = 0.007). The same was found for group 2 (p = 0.005). No significant differences between PLA and PLGA polymers were found. Scanning electron microscopy results indicate a weak adhesion of polymer coatings to ICBM explaining its rather weak retentive effect on overall FITC-BSA release. CONCLUSIONS: Medium molecular size polymers reduce the overall released FITC-BSA from ICBM over time. In clinical practice these polymers may prove ideal for bone substitute materials.


Assuntos
Substitutos Ósseos , Fluoresceína-5-Isotiocianato/análogos & derivados , Polímeros , Soroalbumina Bovina , Animais , Substitutos Ósseos/farmacocinética , Bovinos , Fluoresceína-5-Isotiocianato/farmacocinética , Cinética , Microscopia Eletrônica de Varredura , Soroalbumina Bovina/farmacocinética
2.
Sci Adv ; 5(9): eaaw0672, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31548981

RESUMO

NIR-II fluorescence imaging greatly reduces scattering coefficients for nearly all tissue types at long wavelengths, benefiting deep tissue imaging. However, most of the NIR-II fluorophores suffer from low quantum yields and/or short circulation time that limit the quality of NIR-II imaging. Here, we engineered a supramolecular assembly of protein complex with lodged cyanine dyes to produce a brilliant NIR-II fluorophore, providing a NIR-II quantum yield of 21.2% with prolonged circulation time. Computational modeling revealed the mechanism for fluorescence enhancement and identified key parameters governing albumin complex for NIR-II fluorophores. Our complex afforded high-resolution microvessel imaging, with a 3-hour imaging window compared to 2 min for free dye alone. Furthermore, the complexation strategy was applied to an antibody-derived assembly, offering high-contrast tumor imaging without affecting the targeting ability of the antibody. This study provides a facile strategy for producing high-performance NIR-II fluorophores by chaperoning cyanine dyes with functional proteins.


Assuntos
Meios de Contraste , Corantes Fluorescentes , Neoplasias Experimentais , Imagem Óptica , Soroalbumina Bovina , Animais , Bovinos , Meios de Contraste/química , Meios de Contraste/farmacocinética , Meios de Contraste/farmacologia , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacocinética , Corantes Fluorescentes/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Experimentais/irrigação sanguínea , Neoplasias Experimentais/diagnóstico por imagem , Soroalbumina Bovina/química , Soroalbumina Bovina/farmacocinética , Soroalbumina Bovina/farmacologia
3.
J Microencapsul ; 36(5): 474-484, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31318277

RESUMO

Aim: To improve the long-term storage stability of a bioactive protein and the subsequent colon-targeted release, a double-layer chitosan (CS)-based particle was developed. Methods: To form the double-layer CS-based particle, the second layer was crosslinked onto the single-layer bovine serum albumin (BSA)-loaded CS-based particle. The structure and properties of particles were further investigated. Results: With the second layer, the double-layer particles became more compact, which was important for the inhibition of bioactive protein leakage during storage through strong electrostatic interactions and swelling of the hydrogels. After 30 d of storage, there was only 43.74-49.32% BSA leakage from the C15-TPP/C15-HMP double-layer particles. Moreover, the BSA release in subsequent colon-targeted delivery after storage was 44.02-48.59%. Conclusions: With double-layer shielding and a more compact arrangement, it was possible to reduce bioactive protein leakage over long periods storage and achieve subsequent colon-targeted delivery.


Assuntos
Quitosana/química , Colo/metabolismo , Sistemas de Liberação de Medicamentos , Excipientes/química , Soroalbumina Bovina/administração & dosagem , Animais , Bovinos , Liberação Controlada de Fármacos , Tamanho da Partícula , Estabilidade Proteica , Soroalbumina Bovina/química , Soroalbumina Bovina/farmacocinética
4.
AAPS PharmSciTech ; 20(5): 202, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31140015

RESUMO

Florfenicol (FLO) is a broad-spectrum fluorinated antibiotic used for the treatment of bacterial diseases such as bovine respiratory disease (BRD) in cattle. FLO is a poorly soluble drug in aqueous solution, and its encapsulation in various nanovehicles has been reported to be less than 30%. In this context, the use of bovine serum albumin (BSA) as a nanocarrier for FLO is an interesting approach. BSA is a biocompatible, biodegradable, nontoxic, and nonimmunogenic natural protein, allowing the vehiculization of hydrophilic and hydrophobic drugs with a well-tolerated administration. The present work focuses on the fabrication and characterization of florfenicol-loaded BSA (FLO-BSA NPs), incorporation efficiency, and in vitro release pattern. FLO-BSA NPs nanoparticles were successfully obtained by a simple, low-cost and in a few steps method. The physicochemical properties of the obtained nanoparticles such as size (~ 120 nm), polydispersity index (0.04), and zeta potential (approximately - 40 mV) suggest a high colloidal stability and suitable characteristics for drug delivery. The drug loading reveals a high incorporation of florfenicol in the nanoparticles, in which 33.6 molecules of FLO are encapsulated per each molecule of BSA. The in vitro release profile exhibits an initial stage characterized by the burst effect and then a prolonged release of FLO from the albumin matrix, which is compatible with the Higuchi model and which follows a Fickian diffusion. The results together suggest a suitable tool for future investigations in drug delivery field in order to use this nanomaterial in food, pharmaceutical, and veterinary industry.


Assuntos
Antibacterianos/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/metabolismo , Soroalbumina Bovina/farmacocinética , Tianfenicol/análogos & derivados , Animais , Antibacterianos/administração & dosagem , Antibacterianos/síntese química , Bovinos , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/síntese química , Preparações de Ação Retardada/farmacocinética , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/síntese química , Portadores de Fármacos/farmacocinética , Sistemas de Liberação de Medicamentos/tendências , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas/administração & dosagem , Nanopartículas/química , Tamanho da Partícula , Soroalbumina Bovina/administração & dosagem , Soroalbumina Bovina/síntese química , Tianfenicol/administração & dosagem , Tianfenicol/síntese química , Tianfenicol/farmacocinética
5.
Molecules ; 24(7)2019 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-30970533

RESUMO

Hepatocellular carcinoma (HCC) ranks fifth in occurrence and second in mortality of all cancers. The development of effective therapies for HCC is urgently needed. Anticancer drugs targeted to the liver-specific asialoglycoprotein receptors (ASGPRs) are viewed as a promising potential treatment for HCC. ASGPRs facilitate the recognition and endocytosis of molecules, and possibly vehicles with galactose end groups, by the liver. In this study, bovine serum albumin (BSA) was conjugated with lactose using a thermal treatment. The formation of lactosylated BSA (BSA-Lac) was confirmed by a change of the chemical structure, increased molecular mass, and Ricinus communis lectin recognition. Subsequently, the low-crosslinking BSA-Lac nanoparticles (LC BSA-Lac NPs) and high-crosslinking BSA-Lac nanoparticles (HC BSA-Lac NPs) were synthesized. These nanoparticles presented spherical shapes with a size distribution of 560 ± 18.0 nm and 539 ± 9.0 nm, as well as an estimated surface charge of -26 ± 0.15 mV and -24 ± 0.45 mV, respectively. Both BSA-Lac NPs were selectively recognized by ASGPRs as shown by biorecognition, competition, and inhibition assays using an in vitro model of HCC. This justifies pursuing the strategy of using BSA-Lac NPs as potential drug nanovehicles with selective direction toward hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular/metabolismo , Portadores de Fármacos , Neoplasias Hepáticas/metabolismo , Nanopartículas , Soroalbumina Bovina , Albumina Sérica , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologia , Nanopartículas/química , Nanopartículas/uso terapêutico , Albumina Sérica/química , Albumina Sérica/farmacocinética , Albumina Sérica/farmacologia , Soroalbumina Bovina/química , Soroalbumina Bovina/farmacocinética , Soroalbumina Bovina/farmacologia
6.
Pharm Dev Technol ; 24(5): 575-583, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30457420

RESUMO

The aim of this study was to investigate intravitreal injection of silk fibroin nanoparticles (SFNs) encapsulating bio-macromolecules, achieving enhanced drug bioavailability, and extended retention in retina. SFNs were prepared with regenerated silk fibroin using desolvation method with fluorescein isothiocyanate labeled bovine serum albumin (FITC-BSA) as bio-macromolecular model drug encapsulated. In vitro physicochemical properties and in vitro drug release of FITC-BSA loaded SFNs (FITC-BSA-SFNs) were evaluated. Cytotoxicity, cellular uptake, and retention of FITC-BSA-SFNs were determined in human retinal pigment epithelial cell line (ARPE-19). In addition, in vivo distribution and safety of intravitreally administered FITC-BSA-SFNs were investigated in New Zealand white rabbits. The particle size of FITC-BSA-SFNs was 179.1 ± 3.7 nm with polydispersity index of 0.102 ± 0.033 and the zeta potential was greater than -25 mV. FITC-BSA-SFNs exhibited excellent biocompatibility with no cytotoxicity observed within 24 and 48 h in AREP-19 cells. Compared to FITC-BSA solution, FITC-BSA-SFNs showed enhanced cellular uptake and prolonged retention. Furthermore, FITC-BSA-SFNs achieved accumulated distribution and extended retention in retina in vivo following intravitreal injection compared to a single administration of free drug solution. Therefore, this bio-macromolecule delivery platform based on SFNs could have great potential in the treatment of posterior segment disorders.


Assuntos
Portadores de Fármacos/química , Fibroínas/química , Fluoresceína-5-Isotiocianato/análogos & derivados , Nanopartículas/química , Retina/metabolismo , Soroalbumina Bovina/administração & dosagem , Soroalbumina Bovina/farmacocinética , Animais , Bovinos , Linhagem Celular , Liberação Controlada de Fármacos , Feminino , Fluoresceína-5-Isotiocianato/administração & dosagem , Fluoresceína-5-Isotiocianato/química , Fluoresceína-5-Isotiocianato/farmacocinética , Humanos , Injeções Intravítreas , Coelhos , Retina/citologia , Epitélio Pigmentado da Retina/citologia , Epitélio Pigmentado da Retina/metabolismo , Soroalbumina Bovina/química
7.
Colloids Surf B Biointerfaces ; 174: 216-223, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30465996

RESUMO

We have successfully encapsulated two proteins, bovine serum albumin (BSA) and p53, in chitosan-tripolyphosphate (TPP) nanoparticles at various pH values from 5.5 to 6.5 and delivered the particles to human melanoma cells. The particles have diameters ranging from 180 nm to 280 nm and a zeta potential of +15 to + 40 mV. Cellular uptake of the particles by human skin melanoma cells was evaluated by: (i) fluorescence microscopy and (ii) gel electrophoresis showing that FITC-labeled BSA and p53 could be recovered in the soluble cell fraction after lysis of the cells. Our data also show that the highest cellular uptake takes place at the lowest pH as the particles have the highest positive charge under these conditions. The method we describe appears to be a general method for delivery of proteins to cells using chitosan-TPP nanoparticles as a drug delivery system, since structurally unrelated proteins such as BSA and p53 with different isoelectrical points can be encapsulated in the chitosan-TPP nanoparticles and be effectively internalized by the cells.


Assuntos
Quitosana/análogos & derivados , Sistemas de Liberação de Medicamentos , Melanoma/metabolismo , Melanoma/patologia , Nanopartículas/química , Soroalbumina Bovina/metabolismo , Neoplasias Cutâneas/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Bovinos , Quitosana/química , Humanos , Concentração de Íons de Hidrogênio , Tamanho da Partícula , Soroalbumina Bovina/administração & dosagem , Soroalbumina Bovina/farmacocinética , Neoplasias Cutâneas/patologia , Propriedades de Superfície , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/administração & dosagem , Proteína Supressora de Tumor p53/farmacocinética
8.
Pharm Dev Technol ; 24(3): 329-337, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29781756

RESUMO

Albumin is used as a plasma expander in critically ill patients and for several other clinical applications mainly via intravenous infusion. Oral administration of albumin can improve patient compliance although limited oral bioavailability of proteins is still a major challenge. Although nanomaterials have been extensively utilized for improving oral delivery of proteins, albumin has been utilized only as either a model drug or as a carrier for drug delivery. In the current study, for the first time, chitosan nanoparticles have been developed and extensively optimized to improve oral bioavailability of albumin as a therapeutic protein. Several characterizations have been performed for the albumin-loaded nanoparticles (e.g. drug encapsulation efficiency, DSC, FTIR, particle size, zeta potential, morphology, release kinetics, and enzymatic stability). Nanosized spherical particles were prepared and demonstrated high stability over three months either in a powdered form or as suspensions. Sustained release of albumin over time and high enzymatic stability as compared to the free albumin were observed. In vivo, higher serum concentrations of albumin in normal rabbits and cirrhotic rats were attained following oral and intraperitoneal administrations of the albumin-loaded nanoparticles as compared to the free albumin. The nanoparticles developed in the current study might provide efficient nanovehicles for oral administration of therapeutic albumin.


Assuntos
Quitosana/química , Sistemas de Liberação de Medicamentos , Nanopartículas , Soroalbumina Bovina/administração & dosagem , Administração Oral , Animais , Disponibilidade Biológica , Preparações de Ação Retardada , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Masculino , Tamanho da Partícula , Coelhos , Ratos , Soroalbumina Bovina/química , Soroalbumina Bovina/farmacocinética
9.
Biomaterials ; 192: 15-25, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30415102

RESUMO

Medical coatings cooperated with biomacromolecules can regulate biological events and tissue responses, thus increasing medical implant longevity and providing improved and/or new therapeutic functions. In particular, medical coatings, which can load the correct species and doses of biomacromolecules according to individual diagnoses, will significantly optimize treatment effects and satisfy the rising clinical need of "precision medicine". Herein, we report on a dynamic microporous coating with an ultrafast self-healing property to fulfill the "load-and-play" concept for "precision medicine". A structure-switchable coating based on poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) triblock copolymer network is constructed. The coating can be switched to microporous morphology via a water swelling and freeze-drying process. Then, through a mild thermo-trigger as low as 40 °C, this spongy coating can undergo self-healing to switch back to a pore-free structure within minutes to even 5 s. Based on this dynamic coating, we suggest a simple and versatile method to encapsulate biomacromolecules for surface-mediated delivery. The ultrafast self-healing of the microporous structure enables uniform incorporation of biomacromolecules with an easily achieved high loading of albumin of 16.3 µg/cm2 within 1 min. More importantly, controllable encapsulation can be realized by simple control of the concentration of the loading solution. We further demonstrate that the encapsulated biomacromolecules retained their bioactivity. This work may benefit clinicians with flexibility to provide personalized medical coatings for individual patients during treatment.


Assuntos
Preparações de Ação Retardada/química , Poliésteres/química , Polietilenoglicóis/química , Animais , Stents Farmacológicos , Células Endoteliais da Veia Umbilical Humana , Humanos , Porosidade , Coelhos , Soroalbumina Bovina/administração & dosagem , Soroalbumina Bovina/farmacocinética , Temperatura , Fator A de Crescimento do Endotélio Vascular/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/farmacocinética
10.
ACS Appl Mater Interfaces ; 10(49): 42077-42087, 2018 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-30403472

RESUMO

Integration of multiple diagnostic/therapeutic modalities into a single system with ultrasmall size, excellent photothermal/photodynamic properties, high cellular uptake efficiency, nuclear delivery capacity, rapid renal clearance, and good biosafety is highly desirable for cancer theranostics, but still remains challenging. Here, a novel type of multifunctional nanodots (denoted as BCCGH) was synthesized by mixing bovine serum albumin, carbon dots, and metal ions (Cu2+ and Gd3+), followed by the conjugation with a photosensitizer (HPPH). The nanodots hold great promise for fluorescence/photoacoustic/magnetic resonance/photothermal imaging-guided synergistic photothermal/photodynamic therapy (PDT) because of their appealing properties such as high photothermal conversion efficiency (68.4%), high longitudinal relaxivity (11.84 mM-1 s-1, 7 T), and superior colloidal stability with negligible Gd3+ release. Benefiting from the massive cellular uptake, endoplasmic reticulum/mitochondrion-targeting ability, and mild near-infrared laser irradiation-promoted nuclear delivery of BCCGH, a high anticancer therapeutic efficiency is achieved in the subsequent in vitro PDT. Besides, as revealed by the in vivo/ex vivo results, the nanodots also exhibit excellent tumor accumulation, efficient renal clearance, complete tumor ablation, and exceptional biosafety. To summarize, this work develops a carbon dot-mediated and albumin-based synthetic approach for constructing ultrasmall and multifunctional nanodots, which may hold great potential for cancer theranostics and beyond.


Assuntos
Imagem Multimodal , Neoplasias Experimentais/tratamento farmacológico , Fotoquimioterapia , Pontos Quânticos , Soroalbumina Bovina/química , Animais , Carbono , Linhagem Celular Tumoral , Humanos , Camundongos , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Pontos Quânticos/química , Pontos Quânticos/uso terapêutico , Soroalbumina Bovina/farmacocinética , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Nanomedicine (Lond) ; 13(21): 2759-2776, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30398388

RESUMO

AIM: Investigated strategy exploits the utilization of quercetin as a chemosensitizer for docetaxel (DTX), which was incorporated into albumin nanoparticles (NPs; bovine serum albumin NPs [BSA-NPs]). MATERIAL & METHODS: BSA-NPs containing both drugs were optimized, extensively characterized for different quality attributes and performance was investigated using series of in vitro and in vivo investigations. RESULTS: Co-encapsulated BSA-NPs exhibited size: 209.26 ± 9.84 nm, polydispersibility index: 0.184 ± 0.05 and good entrapment efficiency (∼75% for DTX and ∼68% for quercetin). Higher in vitro cytotoxicity, cell uptake and apoptosis were achieved in MCF-7 cell line. Similarly, higher P-glycoprotein efflux inhibition was observed in MDA-MB-231. About 2.5-fold increase in bioavailability of DTX was achieved with improved antitumor efficacy and reduced in vivo toxicity. CONCLUSION: Developed BSA-NPs provide an effective and safer alternative approach using co-delivery of chemosensitizer.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Docetaxel/administração & dosagem , Nanopartículas/administração & dosagem , Soroalbumina Bovina/química , Animais , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Docetaxel/química , Docetaxel/farmacocinética , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Células MCF-7 , Nanopartículas/química , Quercetina/administração & dosagem , Quercetina/química , Quercetina/farmacocinética , Ratos , Soroalbumina Bovina/administração & dosagem , Soroalbumina Bovina/farmacocinética
12.
ACS Appl Mater Interfaces ; 10(49): 41924-41934, 2018 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-30433758

RESUMO

The core-shell polymeric nanofiber, owing to its better controlled release of embedded or encapsulated drugs in contrast with the single-compartment nanofibers, has been extensively studied for biomedical applications such as tissue engineering and wound healing. Electrospinning with co-axial needles is the dominant technique to fabricate nanofiber mat, however, associated with potential limitations such as high voltage requirement, costly equipment, slow deposition rate, required trained personal, not suitable in situ fabrication, and direct deposition of core-shell nanofibers on the wound at patient bedside. To address the above limitations, the work aims to introduce a novel co-axial airbrushing method to fabricate core-shell nanofibers using a simple setup and low-cost equipment, yet having a unique ability for fabrication at patient bedside and direct deposition on wound bed. Air-brush with a coaxial needle is designed to flow two different polymers solution with model biomolecules through core [PEO (polyethylene oxide)/poly-dl-lactide/PCL (polycaprolactone)] and shell (PCL/PEO) needle for the fabrication of the model core-shell nanofiber. Various processing parameters such as flow rate, air pressure, working distance, and concentration of polymer solution which affect the morphology of core-shell nanofibers were studied and found to have a prominent effect. The PCL-PEO nanofiber possesses a defined shell and core structure, tunable sustained release behavior of model proteins (bovine serum albumin and basic fibroblast growth factor; bFGF), and improved mechanical strength. In vitro interaction of human bone marrow-derived mesenchymal stem cells with core-shell fibers demonstrated the cytocompatibility and proliferative and differentiative (for bFGF loaded) properties of the core-shell nanofiber mat. Co-axial airbrushing can be used as a superior less-expensive technique for the fabrication of biomolecules/drug encapsulated core-shell fibers scaffold at patient bedside, which can mimic complex in vivo environment and could modulate cells behavior close to their in vivo condition for tissue regeneration and wound healing.


Assuntos
Fator 2 de Crescimento de Fibroblastos , Células-Tronco Mesenquimais/metabolismo , Nanofibras/química , Soroalbumina Bovina , Cicatrização/efeitos dos fármacos , Animais , Bovinos , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Fator 2 de Crescimento de Fibroblastos/química , Fator 2 de Crescimento de Fibroblastos/farmacocinética , Fator 2 de Crescimento de Fibroblastos/farmacologia , Humanos , Células-Tronco Mesenquimais/citologia , Poliésteres/química , Poliésteres/farmacocinética , Poliésteres/farmacologia , Soroalbumina Bovina/química , Soroalbumina Bovina/farmacocinética , Soroalbumina Bovina/farmacologia
13.
Artif Cells Nanomed Biotechnol ; 46(sup3): S832-S846, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30449164

RESUMO

The aim of the study was to evaluate the neuroprotective activity of glutathione (GU)-conjugated asiatic acid (AA) loaded albumin nanoparticles and establishing the drug targeting efficiency (DTE) of GU as a selective ligand for brain-targeted delivery. Albumin nanoparticles were prepared by desolvation technique and optimized using quality by design (QbD) approach. GU was conjugated with nanoparticles by carbodiimide reaction and characterized by its size and zeta potential using dynamic light scattering phenomenon. Dialysis bag technique was employed for in-vitro release study and in-vivo brain targeting efficiency was evaluated in Sprague-Dawley rats (75 mg/kg, i.p.). Neuroprotective activity was evaluated against scopolamine-induced dementia in rats. Resultant brain bioavailability of nanoparticles with 100.2 nm size and 71.59% entrapment efficiency (EE), was found 7-fold higher than AA dispersion with 293% DTE for the brain. Conjugated nanoparticles showed significantly high percentage correct alternation (p < .05), low escape latency time (p < .01), cholinesterase inhibition (p < .01) and ameliorated GU levels (p < .01) as compared to diseased animals. GU showed potential to enhance the brain delivery of AA with ameliorated neuroprotective activity due to enhanced bioavailability. This concept can serve as a platform technology for similar potential neurotherapeutics, whose clinical efficacy is still challenging owing to poor bioavailability.


Assuntos
Encéfalo/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Portadores de Fármacos , Nanopartículas , Peptídeos , Soroalbumina Bovina , Animais , Disponibilidade Biológica , Encéfalo/patologia , Bovinos , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Avaliação Pré-Clínica de Medicamentos , Masculino , Nanopartículas/química , Nanopartículas/uso terapêutico , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/farmacocinética , Triterpenos Pentacíclicos/farmacologia , Peptídeos/química , Peptídeos/farmacocinética , Peptídeos/farmacologia , Ratos , Ratos Sprague-Dawley , Soroalbumina Bovina/química , Soroalbumina Bovina/farmacocinética , Soroalbumina Bovina/farmacologia
14.
Biomater Sci ; 7(1): 92-103, 2018 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-30358774

RESUMO

Although photoacoustic imaging combined with second near infrared (NIR II) molecular probes for tumor diagnosis has drawn tremendous attention during the past few decades, the targeted photoacoustic imaging of orthotopic hepatocellular carcinoma (HCC) still remains a challenge due to high liver vascularization and non-specificity of probes in liver tumors. Herein, we report on cyclic arginine-glycine-aspartic acid (cRGD) peptide conjugated ultrasmall CuS nanoparticles (CuS@BSA-RGD NPs) which encapsulate bovine serum albumin (BSA) and possess high optical absorption at 1064 nm. The encapsulation of BSA results in great biocompatibility of CuS@BSA-RGD NPs along with excellent photostability and physiological stability. The cRGD conjugation enables the improvement of tumor uptake of CuS@BSA-RGD NPs by virtue of its positive tumor cell targeting capability. The efficient accumulation of CuS@BSA-RGD NPs in the tumor over time after intravenous administration to orthotopic HCC bearing mice was achieved, which resulted in highly sensitive photoacoustic visualization of the tumor region. Toxicity studies indicate that CuS@BSA-RGD NPs exhibited negligible systemic toxicity in vivo. The results demonstrate that the CuS@BSA-RGD NPs might hold great promise for future imaging and diagnosis of cancer.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Cobre/química , Neoplasias Hepáticas/diagnóstico por imagem , Nanopartículas/química , Peptídeos Cíclicos/química , Técnicas Fotoacústicas/métodos , Soroalbumina Bovina/química , Sulfetos/química , Animais , Cobre/administração & dosagem , Cobre/farmacocinética , Diagnóstico por Imagem/métodos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/administração & dosagem , Peptídeos Cíclicos/administração & dosagem , Peptídeos Cíclicos/farmacocinética , Soroalbumina Bovina/administração & dosagem , Soroalbumina Bovina/farmacocinética , Razão Sinal-Ruído , Sulfetos/administração & dosagem , Sulfetos/farmacocinética , Imagem Corporal Total/métodos
15.
Mater Sci Eng C Mater Biol Appl ; 93: 70-79, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30274103

RESUMO

Capsaicin (CAP) is a secondary metabolite with high therapeutic potential. It displays several bioactive properties including hypolipidemic, antioxidant, anti-inflammatory and analgesic effects. However, CAP presents toxicity to healthy cells and poor pharmacokinetic profile, which is characterized by toxic metabolites and short half-life. In this study, CAP-loaded albumin nanoparticles were obtained by the desolvation-coacervation method. The preparation process was optimized by the application of a factorial design. Nanoparticles presented diameter of about 200 nm, quasi-spherical morphology, encapsulation efficiency of 98.3 ±â€¯7.4%, and negative zeta potential. The in vitro release assay demonstrated a biphasic profile, characterized by a fast release over 12 h followed by a prolonged release rate. Nanoencapsulated CAP showed significant antioxidant activity in an in vitro assay which was concentration - and time-dependent. In addition, the in vivo study demonstrated for the first time that both free and nanoencapsulated drug reduced TNF-alpha concentrations in the absence of inflammatory stimuli model. These novel findings indicate that albumin nanoparticles are potential CAP carriers and that this new drug formulation may be useful in several conditions, including cancer, inflammation, and neuropathic pain.


Assuntos
Capsaicina , Nanocápsulas , Soroalbumina Bovina , Animais , Capsaicina/química , Capsaicina/farmacocinética , Capsaicina/farmacologia , Bovinos , Masculino , Nanocápsulas/química , Nanocápsulas/uso terapêutico , Ratos , Ratos Wistar , Soroalbumina Bovina/química , Soroalbumina Bovina/farmacocinética , Soroalbumina Bovina/farmacologia
16.
ACS Appl Mater Interfaces ; 10(41): 34974-34982, 2018 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-30238746

RESUMO

Many metal-organic complexes showed potent anticancer efficacy, but their clinical applications were limited by the lack of administration route because of their poor solubility. To make metal-organic nanoparticles (MONPs) comprising metal complex drugs is a new formulation strategy for their administration. Herein, we developed a facile synthesis of an MONP composed of bovine serum albumin (BSA), Cu2+, and an anticancer agent, 5-nitro-8-hydroxyquinoline (NQ) with albumin as a nanoreactor. The resultant BSA/Cu/NQ nanoparticle (BSA/Cu/NQ NP) showed good stability in different physiological buffers and could target tumors through the enhanced permeability and retention effect and receptor-mediated cellular uptake. As the BSA/Cu/NQ NP could be readily and efficiently internalized by cancer cells, it showed much higher cytotoxic cancer cells than the NQ + Cu(II) complex and NQ. Therefore, the treatment with BSA/Cu/NQ NP noticeably enhanced the anticancer efficacy without causing systemic toxicity, indicating that such a facile preparation method has great potential to prepare other metal complex nanoparticles for drug delivery.


Assuntos
Complexos de Coordenação , Sistemas de Liberação de Medicamentos , Nanopartículas Metálicas , Neoplasias Experimentais , Nitroquinolinas , Soroalbumina Bovina , Células A549 , Animais , Complexos de Coordenação/química , Complexos de Coordenação/farmacocinética , Complexos de Coordenação/farmacologia , Feminino , Células HeLa , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Nitroquinolinas/química , Nitroquinolinas/farmacocinética , Nitroquinolinas/farmacologia , Soroalbumina Bovina/química , Soroalbumina Bovina/farmacocinética , Soroalbumina Bovina/farmacologia
17.
J Pharm Sci ; 107(10): 2686-2693, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30156185

RESUMO

Hydrogen sulfide (H2S) has been recently recognized as a gaseous signaling molecule that controls various biological activities. In the present study, we developed sulfo-albumin as a macromolecular H2S prodrug for therapeutic use, in which multisulfide groups (source of H2S) were conjugated with bovine serum albumin through a covalent linkage. In an in vitro study on H2S release in phosphate buffered saline solution, we found that H2S was released from sulfo-albumin in the presence of 5-mM glutathione but not in its absence. Furthermore, sulfo-albumin was taken up by RAW 264.7 cells, and it released H2S in cells but not in plasma. These results indicate that H2S can be selectively released from sulfo-albumin in cells. 111In-labeled sulfo-albumin predominantly accumulated in the liver, dependent upon the number of sulfide groups, after intravenous injection in mice. In a carbon tetrachloride-induced acute liver injury mouse model, sulfo-albumin significantly suppressed the increase in plasma aspartate aminotransferase and alanine aminotransferase activities, which are indicators of hepatocyte injury, after intravenous injection. These findings indicate that sulfo-albumin is a promising compound for the treatment of hepatic injuries.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Sulfeto de Hidrogênio/farmacologia , Sulfeto de Hidrogênio/farmacocinética , Pró-Fármacos/farmacologia , Pró-Fármacos/farmacocinética , Soroalbumina Bovina/farmacologia , Soroalbumina Bovina/farmacocinética , Animais , Aspartato Aminotransferases/metabolismo , Tetracloreto de Carbono/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Glutationa/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Sulfetos/farmacocinética , Sulfetos/farmacologia
18.
Mater Sci Eng C Mater Biol Appl ; 91: 247-254, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30033252

RESUMO

In recent years, there has been a significant increase in strategies for the development of small intestine (and colon)-specific oral drug-delivery systems to maximize the efficiency of therapeutic agents and reduce side effects. However, only a few strategies are capable of working in the complicated environment of the human intestinal tract. In this study, the preparation of a basic pH/temperature-responsive co-polymer (p-NIVIm) and its in-vitro-drug delivery function in the pH range of 1-8 and temperature range of 25-42 °C are reported. The basic copolymer was prepared by radical copolymerization of N-isopropyl acryl amide (NIPAAm) and N-vinylimidazole (VIm). The lower critical solution temperature (LCST) of p-NIVIm was higher in stomach pH (~1.0) conditions (36.5-42 °C) and lower in small intestine and/or colon pH (~8.0) conditions (35.8-38.2 °C). The ability to uptake a model protein (BSA) at body temperature and to release it in conditions of 37 °C and pH 1-8 was determined. The drug loading capacity (0.231 mg per 1.0 mg copolymer) and efficiency (92.4%) were high at 37 °C/pH 7. The drug carrier showed a slow release pattern at pH 1 (~0.084 mg; ~35%) and then a sudden release pattern (~0.177 mg; ~73%) at pH 8. The cytotoxicity of p-NIVIm to MCF-7 cells in vitro was minimal at concentrations <168.9 µg/mL after 72 h. The prepared copolymer with its pH-/temperature-responsive protein-entrapping and -releasing behavior at body temperature may potentially be applied as a novel small intestine (and colon)-specific oral drug delivery system.


Assuntos
Colo/metabolismo , Intestino Delgado/metabolismo , Polímeros , Soroalbumina Bovina , Administração Oral , Animais , Bovinos , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Polímeros/química , Polímeros/farmacocinética , Polímeros/farmacologia , Soroalbumina Bovina/química , Soroalbumina Bovina/farmacocinética , Soroalbumina Bovina/farmacologia
19.
J Control Release ; 284: 122-132, 2018 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-29894710

RESUMO

Microneedle patches, arrays of micron-scale projections that penetrate skin in a minimally invasive manner, are a promising tool for transdermally delivering therapeutic proteins. However, current microneedle fabrication techniques are limited in their ability to fabricate microneedles rapidly and with a high degree of control over microneedle design parameters. We have previously demonstrated the ability to fabricate microneedle patches with a range of compositions and geometries using the novel additive manufacturing technique Continuous Liquid Interface Production (CLIP). Here, we establish a method for dip coating CLIP microneedles with protein cargo in a spatially controlled manner. Microneedle coating mask devices were fabricated with CLIP and utilized to coat polyethylene glycol-based CLIP microneedles with model proteins bovine serum albumin, ovalbumin, and lysozyme. The design of the coating mask device was used to control spatial deposition and loading of coated protein cargo on the microneedles. CLIP microneedles rapidly released coated protein cargo both in solution and upon insertion into porcine skin. The model enzyme lysozyme was shown to retain its activity throughout the CLIP microneedle coating process, and permeation of bovine serum albumin across full thickness porcine skin was observed after application with coated CLIP microneedles. Protein-coated CLIP microneedles were applied to live mice and showed sustained retention of protein cargo in the skin over 72 h. These results demonstrate the utility of a versatile coating platform for preparation of precisely coated microneedles for transdermal therapeutic delivery.


Assuntos
Sistemas de Liberação de Medicamentos/instrumentação , Microinjeções/instrumentação , Soroalbumina Bovina/administração & dosagem , Administração Cutânea , Animais , Bovinos , Feminino , Camundongos Endogâmicos BALB C , Agulhas , Proteínas/administração & dosagem , Proteínas/farmacocinética , Soroalbumina Bovina/farmacocinética , Pele/metabolismo , Absorção Cutânea , Suínos , Adesivo Transdérmico
20.
Biomacromolecules ; 19(6): 2238-2247, 2018 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-29689157

RESUMO

In prior research it has been demonstrated that methylated ß-cyclodextrins-threaded acid-labile polyrotaxanes (Me-PRXs) exhibit a lower critical solution temperature (LCST) and form coacervate droplets above their LCST. In this study, the encapsulation of proteins in coacervate droplets and the pH-responsive release of proteins, through the acid-induced dissociation of the Me-PRX, were investigated. The coacervate droplets encapsulate various proteins, such as bovine serum albumin (BSA), lysozyme, and ß-galactosidase, at pH 7.4, into their hydrophobic inner phase. Concomitant with the pH-dependent dissociation of the Me-PRXs, the coacervates degraded below pH 6.5 and released encapsulated proteins, with the intrinsic activity of proteins maintained. Additionally, the subcutaneous injection of coacervate droplets encapsulating BSA in mice revealed that the retention time of the BSA at the injection site was prolonged compared to that of free BSA. Altogether, the coacervate droplets of the Me-PRX would be utilized as a new class of pH-responsive and injectable carrier for the controlled release of therapeutic proteins.


Assuntos
Portadores de Fármacos , Muramidase , Rotaxanos , Soroalbumina Bovina , beta-Galactosidase , Animais , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Concentração de Íons de Hidrogênio , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Muramidase/química , Muramidase/farmacocinética , Muramidase/farmacologia , Rotaxanos/química , Rotaxanos/farmacocinética , Rotaxanos/farmacologia , Soroalbumina Bovina/química , Soroalbumina Bovina/farmacocinética , Soroalbumina Bovina/farmacologia , beta-Galactosidase/química , beta-Galactosidase/farmacocinética , beta-Galactosidase/farmacologia
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