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1.
Braz Oral Res ; 33: e086, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31483052

RESUMO

Treatment of patients with bisphosphonate usage is a significant concern for oral surgeons because it interferes with jaw bone turnover and regeneration. In case of adverse effects manifesting related to bisphosphonate use, oral surgeons are usually treating and keep the patient's symptoms under control. In this study, we aimed to investigate a new treatment protocol for medication-related osteonecrosis of the jaw (MRONJ). This treatment protocol consisted of administering human parathyroid hormone (hPTH) loaded chitosan microspheres which were prepared by ionotropic gelation method or/and the prepared microspheres were suspended in a poloxamer gel. After in-vitro optimization studies, the efficacy of the chosen formulations was evaluated in-vivo studies. Zoledronic acid was administered daily to forty-eight adult female Sprague-Dawley rats, divided into four experimental groups, at a daily concentration of 0.11 mg/kg over three weeks to induce the MRONJ model. At the end of this period, maxillary left molar teeth were extracted. In the first group, the subjects received no treatment. In the negative control group, poloxamer hydrogel containing empty microspheres were immediately applied to the soft tissues surrounding the extraction socket. The treatment group-1 was treated with local injections of poloxamer hydrogel containing hPTH. The treatment group-2 was treated with a single local injection of poloxamer hydrogel containing hPTH-loaded chitosan microspheres. Both treatment groups received a total of 7 µg of hPTH at the end of the treatment protocol. Our study demonstrates successful attenuation of MRONJ through a local drug delivery system combined with hPTH, as opposed to previously attempted treatment strategies.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Quitosana/farmacologia , Maxila/efeitos dos fármacos , Hormônio Paratireóideo/farmacologia , Animais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/tratamento farmacológico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Quitosana/uso terapêutico , Preparações de Ação Retardada , Feminino , Humanos , Maxila/patologia , Microesferas , Modelos Animais , Hormônio Paratireóideo/uso terapêutico , Poloxâmero/administração & dosagem , Poloxâmero/química , Ratos Sprague-Dawley , Ácido Zoledrônico/efeitos adversos
2.
AAPS PharmSciTech ; 20(7): 304, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31502233

RESUMO

The objective of this study is to elucidate the combined effects of a novel type of material being investigated as a new excipient, an octenylsuccinate-modified dendrimer-like biopolymer (OS-DLB) and poloxamer (PLX), on the solubility of poorly water-soluble compounds. Phenytoin (PHT), griseofulvin (GSF), ibuprofen (IBU), and loratadine (LOR) were used as model compounds. Phase solubility measurements were conducted to determine the relative proportions of API, OS-DLB, and PLX that result in the most stable dendrimeric complexes. The solubilizing power of OS-DLB increases with increasing hydrophobicity of the solute. In the presence of PLX, the solubilization effect of OS-DLB is modestly accentuated for the most hydrophobic drugs (IBU and LOR) but has no effect on the least hydrophobic one (PHT). The maximum potentiation effect of PLX on the solubilizing properties of OS-DLB was observed for GSF, the drug of intermediate hydrophobicity. Three different types of solubilization profiles were obtained in the study. All three different profiles can be appropriately described by a single solubilization model, depending on the specific parameter values. The defining parameters of the model reflect the hydrophobicity of the drug on the one hand and, on the other hand, the inherent tendency of the drug (crystal lattice energy) toward crystallization.


Assuntos
Biopolímeros/química , Dendrímeros/química , Liberação Controlada de Fármacos , Griseofulvina/química , Interações Hidrofóbicas e Hidrofílicas , Nanoestruturas , Poloxâmero/química
3.
Chem Commun (Camb) ; 55(73): 10920-10923, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31441463

RESUMO

The development of new NIR-II fluorophores, particularly those with facile syntheses, high fluorescence quantum yields, and stable and tunable photophysical properties, is challenging. Herein, we report a new class of small molecular NIR-II fluorophores based on aza-dipyrromethene boron difluoride (aza-BODIPY) dyes. We demonstrate promising photophysical properties of these dyes, such as large Stokes shift, superior photostability, and good fluorescence brightness as nanoparticles in aqueous solution. Because of these properties and high resolution and deep penetration NIR-II imaging ability, the aza-BODIPY based dyes show great potential as NIR-II imaging agents.


Assuntos
Compostos de Boro/química , Corantes Fluorescentes/química , Imagem Óptica/métodos , Pirróis/química , Animais , Compostos de Boro/síntese química , Compostos de Boro/efeitos da radiação , Compostos de Boro/toxicidade , Linhagem Celular Tumoral , Teoria da Densidade Funcional , Desenho de Drogas , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/efeitos da radiação , Corantes Fluorescentes/toxicidade , Raios Infravermelhos , Camundongos , Modelos Químicos , Nanopartículas/química , Poloxâmero/química , Pirróis/síntese química , Pirróis/efeitos da radiação , Pirróis/toxicidade
5.
Phys Chem Chem Phys ; 21(25): 13746-13757, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31209450

RESUMO

The phase behaviour as a function of temperature is explored for pure phospholipid (DPPC) and hybrid lipid-polymer (DPPC/Pluronic L64) bilayers with the aid of atomistic MD simulations. The range of the fixed-temperature simulations includes temperatures below and above the known melting temperature (Tm) for DPPC membranes. For the pure lipid bilayer, the main phase transition is discontinuous, as verified by the abrupt changes observed in the membrane structure, elasticity and the lipid diffusivity near the critical temperature Tm, which lies in the region 298.15-303.15 K. A pre-transition step is detected at 298.15 K which has been identified as the ripple phase (Pß'), where ordered and disordered lipids coexist, causing thickness fluctuations. In the ordered gel phase, the positional ordering as assessed by the lipid radial distribution functions is long-range and some degree of hexagonal packing is measured. The hybrid bilayers on the other hand, transform from a more ordered to a disordered phase in a continuous manner, without finite jumps in their properties. No signs of the ripple phase are identified and the ordered phase exhibits very limited hexagonal packing and some positional ordering that decays fast. The effect of the inserted polymers in the two phases is reversed; at low temperatures, they render the membrane thinner, less cohesive and less ordered compared to the pure one, with the lipids assuming faster diffusion rates, whereas at high temperatures, the polymer interaction with the lipids acts reducing their diffusivity, but also increasing the lipid tail ordering and the membrane stiffness. The ability of the amphiphilic L64 copolymers to change the nature of the main phase transition of lipid membranes and their properties both in the ordered and the disordered phase is of vital importance for the prediction of both the efficacy of hybrid lipid/polymer nanoparticles as drug delivery vehicles as well as their potential adverse implications during interactions with healthy cell membranes.


Assuntos
Bicamadas Lipídicas/química , Modelos Moleculares , Fosfolipídeos/química , Poloxâmero/química , Cristalização , Difusão , Cinética , Membranas Artificiais , Modelos Químicos , Transição de Fase , Termodinâmica , Temperatura de Transição
6.
Biomater Sci ; 7(9): 3801-3811, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31237275

RESUMO

Nanotechnology-based systems have been proposed for rectal drug delivery, often rendering promising outcomes concerning disease prophylaxis or therapeutics. However, nanocarriers often feature reduced colorectal retention when administered in liquid vehicles (enemas). Semi-solid platforms may be considered as alternative but usually result in limited local distribution. Thermosensitive enemas undergoing sol-gel transition just below body temperature have been used for abbreviating these issues, but the actual impact on the colorectal distribution and retention of incorporated nanosystems is not clear. We prepared and characterized a potential drug delivery platform by incorporating poly(lactic-co-glycolic acid)-based nanoparticles (170-180 nm mean hydrodynamic diameter) into a poloxamer 407-based thermosensitive enema (NPs-in-thermo). The system featured suitable functional properties for rectal administration such as sol-gel transition temperature of approximately 27-28 °C, sol-gel transition time of 1.6 min, and viscosity around 31 and 2100 mPa s at 20 °C and 37 °C, respectively. NPs-in-thermo presented osmolality and pH values deemed compatible with the colorectal compartment, as well as reduced toxicity to the Caco-2 colorectal cell line. The composite system was also used to incorporate the anti-HIV microbicide model drug dapivirine. In vitro studies showed that dapivirine-loaded NPs-in-thermo was able to provide overall faster drug release as compared to dapivirine directly dispersed into phosphate buffered saline or the thermosensitive enema base. Finally, NPs-in-thermo was tested for distribution and retention in a mouse model by in vivo and ex vivo near infrared imaging. Qualitative and semi-quantitative data indicated that NPs exhibited slower but overall wider distribution and enhanced retention in the distal colon of mice treated intrarectally with NPs-in-thermo, namely when compared to NPs dispersed in liquid phosphate buffered saline. Overall, our data support that thermosensitive enemas may provide suitable platforms for the rectal administration of polymeric NPs, namely in the context of drug delivery.


Assuntos
Colo/metabolismo , Enema/métodos , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacocinética , Reto/metabolismo , Administração Retal , Animais , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/farmacocinética , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos , Humanos , Camundongos Endogâmicos ICR , Concentração Osmolar , Tamanho da Partícula , Transição de Fase , Poloxâmero/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Pirimidinas/administração & dosagem , Pirimidinas/farmacocinética , Temperatura Ambiente , Distribuição Tecidual
7.
Phys Chem Chem Phys ; 21(24): 13005-13013, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31165825

RESUMO

Cubosomes and hexosomes are emerging platforms for drug and nutraceutical delivery applications. In addition to common high- and low-energy batch emulsification methods for the preparation of these nano-self-assemblies, it is important to introduce suitable microfluidic devices with a precision control of the flow parameters for their continuous production. Microfluidics has several advantages including cost effectiveness, short-production time, and control of the nanoparticle size and size distribution. In the present study, a hydrodynamic flow focusing polyimide microfluidic device was employed for the continuous production of hexosomes based on docosahexaenoic acid monoglyceride (MAG-DHA), in the presence of the stabilizer Pluronic F127. The size, structural, morphological and size characterizations of the continuously produced MAG-DHA nanodispersions were investigated through an integrated approach involving synchrotron small angle X-ray scattering, dynamic light scattering, and cryogenic transmission electron microscopy. We report on a simple process for the microfluidic synthesis of hexosomes with sizes ranging from 108 to 138 nm and relatively narrow size distributions as the polydispersity indices were in the range of 0.14-0.22. At the applied total volumetric flow rates (TFRs) ranging of 50-150 µL min-1 and flow rate ratios (FRRs) of 10-30, it was evident from SAXS findings that ethanol has only a slight effect on the lattice parameter of the internal inverse hexagonal (H2) phase of the produced hexosomes. In addition to hexosomes, cryo-TEM observations indicated the coexistence of vesicular structures and smaller nano-objects. The formation of these nano-objects that are most likely normal micelles was also confirmed by SAXS, particularly on increasing FRR from 10 to 20 or 30 at TFR of 150 µL min-1. Taking into account the reported positive health effects of MAG-DHA, which is a long-chain omega-3 (ω-3) polyunsaturated fatty acid (PUFA) monoglyceride, in various disorders including cancer, the produced hexosomes are attractive for the delivery of ω-3 PUFAs, drugs, nutraceuticals, and their combinations.


Assuntos
Ácidos Docosa-Hexaenoicos/química , Ácidos Graxos Ômega-3/química , Dispositivos Lab-On-A-Chip , Nanopartículas/química , Hidrodinâmica , Micelas , Monoglicerídeos/química , Tamanho da Partícula , Poloxâmero/química
8.
Pharm Res ; 36(7): 107, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31111248

RESUMO

PURPOSE: To provide new insights into how protein-surfactant competitive adsorbtion and corresponding surface tension reduction properties at the air-water and oil-water interface are impacted by the type of protein and the associated protein surface rheology. METHOD: Interfacial Rheology was utilized to obtain surface G' and G" as a function of frequency. Force tensiometry was utilized to obtain changes in surface tension as a function of surfactant concentration. The impact on surface properties of two different proteins i.e. BSA and Lysozyme was investigated as a function of surfactant concentration i.e. polysorbates PS 20, PS 80 and Poloxomer (Kolliphor P188). RESULTS: Surface tension and interfacial tension measurements for BSA showed that in mixed BSA/polysorbate surfactant systems, BSA dominates the interfacial behavior at both the air-water and oil-water interfaces, until a high polysorbate concentration of 0.1 mg/ml. At these high polysorbate concentrations a mixed BSA-Polysorbate interfacial layer is formed as corroborated by the surface elasticity values being lower than that of pure BSA but higher than that of pure Polysorbate. For Kolliphor, it was observed that Kolliphor was unable to displace BSA at any concentration. This is corroborated by the high surface elasticity of the BSA which is maintained in the presence of Kolliphor. Surface and interfacial tension measurements for lysozyme show that for mixed lysozyme/polysorbate surfactant systems, the surface tension values are lower than that exhibited by either the lysozyme or the polysorbate surfactants. This potentially indicates the formation of a mixed layer of lysozyme and polysorbate. At the high polysorbate concentrations probed, the surface elasticity values are however closer to that of pure polysorbates, indicating that the mixed layer may be more heavily polysorbate dominated, especially at high polysorbate concentrations. For Kolliphor, the response was similar to that seen in the Kolliphor-BSA system in which the Kolliphor was not able to displace the protein i.e. Lysozyme. CONCLUSIONS: In conclusion, it was seen that competitive adsorption between proteins and common excipient surfactants is dictated by the type of protein and its effective structuring/rigidity at the surface as reflected through surface elasticity and surface tan delta values. BSA was seen to exhibit a higher surface elasticity than lysozyme, and therefore has a more rigid structure and is more competitive at the interface.


Assuntos
Muramidase/química , Poloxâmero/química , Polissorbatos/química , Soroalbumina Bovina/química , Tensoativos/química , Adsorção , Elasticidade , Excipientes , Polietilenoglicóis , Reologia/métodos , Estearatos , Propriedades de Superfície , Tensão Superficial
9.
Drug Discov Ther ; 13(2): 62-69, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31080205

RESUMO

In the present study, silver nanoparticles (AgNPs) were synthesized by green synthesis using Psidium guajava aqueous extract (PE) as a reducing agent and silver nitrate (AgNO3) as a precursor. The obtained AgNPs showed maximum absorbance at 455 nm. The results from energy-dispersive X-ray spectroscopy demonstrate Ag signal at 88.33% weight. The particle image under scanning electron microscopy is spherical shape. The average size of the freshly prepared AgNPs is 96 ± 4 nm but is dramatically increases during storage due to particle aggregation. Coating AgNPs with polymeric micelles of poloxamer 407 (F127) at the suitable ratio can decrease the size of the freshly prepared AgNPs to 70.4 ± 0.8 nm and significantly prevent AgNPs from aggregation. The obtained coated AgNPs showed high effective on inhibition of Candida albicans. Isotonic solutions of 0.9% NaCl and phosphate buffer solution pH 7.4 can cause some extend of aggregation and increase the particle size of the coated AgNPs but the increased size is in the colloidal range that no precipitation occurs during 90 days at room temperature. From our results, it is suggested that the 1:1 ratio of AgNPs/F127 is the most suitable ratio to obtain the AgNPs loaded polymeric micelles with high stability, small particle size, and high inhibitory activity against C. albicans. These AgNPs are the promising antifungal nanomaterials for further study in animal model.


Assuntos
Antifúngicos/síntese química , Candida albicans/efeitos dos fármacos , Extratos Vegetais/química , Psidium/química , Prata/química , Antifúngicos/química , Antifúngicos/farmacologia , Química Verde , Nanopartículas Metálicas/química , Micelas , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Poloxâmero/química , Espectrometria por Raios X
10.
Pharm Dev Technol ; 24(7): 891-901, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31062987

RESUMO

This study was conducted to develop an in situ thermosensitive gel containing sertaconazole-loaded nanostructured lipid carriers (NLCs) for prolonged ocular drug delivery. To this end, sertaconazole-loaded NLCs (sertaconazole-NLCs) were prepared by emulsification solvent-diffusion method and the effects of different formulation variables were assessed using the fractional factorial design. Then, optimized sertaconazole-NLCs were incorporated into the pluronic F127 (PF127)/hydroxy propylmethylcellulose (HPMC) K4M hydrogel. The formulations were examined for pH, gelation temperature, rheological properties, in vitro permeation studies, and anti-fungal activity. The optimized sertaconazole-NLCs showed a mean particle size of 272.40 nm, encapsulation efficiency of 89.97%, zeta potential of 12.9 mV, and polydispersity index of 0.31. All the in situ formulations had acceptable pH, ranging from 5.89 to 6.28. The gelation temperature of the optimized formulation was 35.1 °C after dilution with simulated tear fluid (STF). Sertaconazole-NLCs showed a higher antifungal activity and permeation through the bovine cornea compared to the free drug and the in situ gel formulation. The cornea penetration of sertaconazole for the in situ gel of NLCs was also comparable to that for free drug. The obtained results indicated that the prepared nanocomposite system may have potential for treatment of fungal keratitis.


Assuntos
Antifúngicos/administração & dosagem , Portadores de Fármacos/química , Imidazóis/administração & dosagem , Lipídeos/química , Nanopartículas/química , Tiofenos/administração & dosagem , Animais , Antifúngicos/farmacocinética , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candidíase/tratamento farmacológico , Bovinos , Córnea/metabolismo , Liberação Controlada de Fármacos , Hidrogéis/química , Imidazóis/farmacocinética , Imidazóis/farmacologia , Ceratite/tratamento farmacológico , Nanopartículas/ultraestrutura , Poloxâmero/química , Temperatura Ambiente , Tiofenos/farmacocinética , Tiofenos/farmacologia
11.
Pharm Res ; 36(6): 83, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30989413

RESUMO

PURPOSE: Salinomycin (SAL) is a polyether compound that exhibits strong antimicrobial as well as anticancer activity. Nanomedicine has been at the forefront of drug delivery research with the aim of increasing the efficacy, specificity and reduce toxicity of drugs. There is an intersection between infection and cancer, and cancer patients are prone to bacterial infections. In this study, polymeric micelles were prepared using Pluronic® F127 (PM) to encapsulate SAL (PM_SAL) with the view of enhancing antimicrobial and anticancer activity. METHODS: A Quality by Design (QbD) approach was utilized to synthesize PM_SAL, and nanoformulation activity was determined against bacterial (S. aureus, MRSA and E. coli). Effects on cancer cell line A549, i.e. cell viability, prevention of P-gp efflux, vimentin expression, effects on migratory ability of A549 cells. Anticancer activity was determined by ability to eradicate cancer stem-like cells. RESULTS: PM_SAL demonstrated only efficacy against MRSA, being even higher than that obtained with SAL. In A549 cells, a 15-fold increase in P-gp's expression as well as a significant decrease of the cell's migration, was observed. CONCLUSIONS: PM_SAL can interfere with the oncogenic protein VIM, involved in the crucial mechanisms EMT, downregulating its expression. Altogether data obtained indicates that this antibiotic and the developed polymeric micelle system is a very promising inhibitor of tumor cell growth.


Assuntos
Anti-Infecciosos/química , Antineoplásicos/química , Portadores de Fármacos/química , Poloxâmero/química , Piranos/química , Células A549 , Anti-Infecciosos/farmacologia , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Escherichia coli/efeitos dos fármacos , Humanos , Micelas , Células-Tronco Neoplásicas/citologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Tamanho da Partícula , Piranos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Propriedades de Superfície , Vimentina/genética
12.
Artif Cells Nanomed Biotechnol ; 47(1): 1234-1240, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30966834

RESUMO

Microbicides based on hydrogel have become an effective way to prevent the HIV replication and transmission because of their convenience and prolonging drug release. In this study, a hybrid thermo-sensitive hydrogel constituted by nanosized layered double hydroxides and poloxamer 407 (P407) was constructed and co-loaded with both hydrophobic and hydrophilic drug. The LDH-P407 hydrogel could achieve sol-gel transition at body temperature. The in vivo experiment showed that LDH-P407 hydrogel can achieve controlled release of theaflavin and Nile red (hydrophobic drug model) into blood by vaginal drug delivery, meanwhile the hydrogel showed barely mucosal irritation. In addition, ex vivo experiment showed that the nifeviroc-loaded LDH-P407 hydrogel was able to specifically bind co-receptor CCR5 of DCs cells. Therefore, the LDH-P407 hydrogel would be a promising carrier for intravaginal delivery of anti-HIV drugs.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/química , Portadores de Fármacos/química , Hidrogéis/química , Hidróxidos/química , Temperatura Ambiente , Administração Intravaginal , Animais , Fármacos Anti-HIV/farmacologia , Antagonistas dos Receptores CCR5/administração & dosagem , Antagonistas dos Receptores CCR5/química , Antagonistas dos Receptores CCR5/farmacologia , Portadores de Fármacos/farmacocinética , Interações Hidrofóbicas e Hidrofílicas , Hidróxidos/farmacocinética , Poloxâmero/química , Coelhos , Reologia , Distribuição Tecidual
13.
Int J Pharm ; 563: 249-258, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-30965120

RESUMO

Azelaic acid (AZA) is a dicarboxylic acid that is topically used in the treatment of acne and rosacea since it possesses antibacterial and keratolytic activity. The primary objective of this study was to develop an AZA nanocrystal suspension. It is expected that improved solubility and dissolution rate will result in advanced biopharmaceutical properties, primarily the dermal bioavailability. Furthermore, a topical nanocrystal AZA-loaded hydrogels composed of Pluronic® F127 and hyaluronic acid mixture that are able to deliver AZA into the stratum corneum and deeper skin layers were considered. This study was conducted in order to: 1) determine the effect of non-ionic Polysorbate 60 on the stabilization and particle size of the AZA nanocrystals, as well as the effect of Pluronic® F127, used as an in situ gelation agent, and hyaluronic acid on the viscoelastic properties and the drug release of composed hydrogels, 2) determine the relationship between the rheological properties of the gels and the penetration of AZA into the stratum corneum. The composed hydrogels revealed pseudoplastic flow behaviour. The increase in Pluronic® F127 concentration induced a domination of elastic over viscous behaviour of the gels. The gel containing 15% of Pluronic® F127, 1% of hyaluronic acid and lyophilised 10% nanocrystal AZA suspension was considered to be an optimal formulation, since it possessed the rheological and drug delivery properties desirable for an in situ gelling platform for dermal application.


Assuntos
Ácidos Dicarboxílicos/administração & dosagem , Hidrogéis/administração & dosagem , Nanopartículas/administração & dosagem , Poloxâmero/administração & dosagem , Polissorbatos/administração & dosagem , Pele/metabolismo , Administração Cutânea , Adulto , Ácidos Dicarboxílicos/química , Liberação Controlada de Fármacos , Feminino , Humanos , Hidrogéis/química , Nanopartículas/química , Poloxâmero/química , Polissorbatos/química , Absorção Cutânea
14.
Pharm Nanotechnol ; 7(2): 147-161, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30931866

RESUMO

BACKGROUND: Miniaturization of nanosuspensions preparation is a necessity in order to enable proper formulation screening before nanosizing can be performed on a large scale. Ideally, the information generated at small scale is predictive for large scale production. OBJECTIVE: This study was aimed to investigate the scalability when producing nanosuspensions starting from a 10 g scale of nanosuspension using low energy wet ball milling up to production scales of 120 g nanosuspension and 2 kg nanosuspension by using a standard high energy wet ball milling operated in batch mode or recirculation mode, respectively. METHODS: Two different active pharmaceutical ingredients, i.e. curcumin and hesperetin, have been used in this study. The investigated factors include the milling time, milling speed, and the type of mill. RESULTS: Comparable particle sizes of about 151 nm to 190 nm were obtained for both active pharmaceutical ingredients at the same milling time and milling speed when the drugs were processed at 10 g using low energy wet ball milling or 120 g using high energy wet ball milling in batch mode, respectively. However, an adjustment of the milling speed was needed for the 2 kg scale produced using high energy wet ball milling in recirculation mode to obtain particle sizes comparable to the small scale process. CONCLUSION: These results confirm in general, the scalability of wet ball milling as well as the suitability of small scale processing in order to correctly identify the most suitable formulations for large scale production using high energy milling.


Assuntos
Curcumina/química , Excipientes/química , Hesperidina/química , Nanopartículas/química , Composição de Medicamentos , Poloxâmero/química , Colato de Sódio/química , Suspensões/química , Tecnologia Farmacêutica
15.
AAPS PharmSciTech ; 20(3): 134, 2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30830481

RESUMO

Nasal nanovesicular gels of buspirone hydrochloride (BH) were prepared and characterized aiming for sustained delivery and enhancing bioavailability. Buspirone hydrochloride has low bioavailability of about 4% after oral administration due to first pass metabolism. Buspirone hydrochloride nanovesicles were formulated by thin film hydration method (TFH). The selected nanovesicular formulation was incorporated into two types of in situ gels (pH-induced and thermoreversible) using carbopol 974P and poloxamer 407 (P407), respectively, together with different mucoadhesive polymers. The in situ gels were examined for pH, gelling capability, viscosity, content uniformity, mucoadhesiveness, and in vitro drug release. The ex vivo permeation performance of the in situ gel formulations that showed the most sustained release was also assessed. The in vivo study was done by the determination of BH blood level in albino rabbits after nasal administration. Results revealed that nanovesicles prepared using Span 60 and cholesterol in a ratio of 80:20 showed the highest EE% (70.57 ± 1.00%). The ex vivo permeation data confirmed higher permeability figures for carbopol formulation in comparison to poloxamer formulations. The in vivo study data showed an increase of 3.26 times in BH bioavailability when formulated into the carbopol nanovesicular in situ gel relative to control (nasal drug solution).


Assuntos
Ansiolíticos/administração & dosagem , Buspirona/administração & dosagem , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Acrilatos/química , Administração Intranasal , Animais , Ansiolíticos/química , Ansiolíticos/farmacocinética , Disponibilidade Biológica , Buspirona/química , Buspirona/farmacocinética , Técnicas In Vitro , Masculino , Mucosa Nasal/metabolismo , Permeabilidade , Poloxâmero/química , Coelhos , Ovinos , Viscosidade
16.
Mater Sci Eng C Mater Biol Appl ; 99: 1350-1361, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30889669

RESUMO

Local administration of antimicrobial agents is the first therapeutic approach for the treatment of Candida albicans infections. The duration of contact of formulations with the vaginal mucosa is critical for therapeutic efficacy. This study describes the development of organogels employing an oil phase composed of oleic acid (OA) and an aqueous phase consisting of the poloxamer PL407, alone or in association with PL188, together with 0.25-1% sodium alginate (SA), in order to obtain an intravaginal drug delivery system capable of modulating the release of voriconazole (VRC). VRC was solubilized in oleic acid homogenized with the PL-SA aqueous phase, at a final concentration of 5 mg/mL. Physicochemical characterization was performed for evaluation of the influence of SA on organogel structural organization, biopharmaceutical properties, pharmacological efficacy, and cytotoxicity, envisaging use of the formulation for the treatment of vaginal candidiasis. The enthalpy variation values showed greater changes in the presence of PL188 and after the incorporation of SA or VRC in the organogels. Rheological analysis showed Tsol-gel values in the ranges 11-39 °C and 27-30 °C for the OA-PL407 and OA-PL407-188 formulations, respectively. Oscillatory analysis of OA-PL407-188 showed that G' was ~20-fold higher than G″, even after submitting the formulation to temperature variation. VRC-OA-PL407 showed fast drug release from 0.5 to 4 h, maintaining total release (~100%) up to 24 h. The incorporation of SA in the organogels enabled modulation of VRC release, with different release percentages for 0.25% SA (~75%), 0.5% SA (~55%), and 1% SA (~35%). The formulation was non-cytotoxic towards HeLa and Vero cell lines. In diffusion tests, it was able to prevent the growth of Candida albicans and Candida krusei. In conclusion, the results suggested that OA-PL407-188-SA organogels could be possible new systems for VRC delivery, with potential for use in future vaginal applications.


Assuntos
Alginatos/química , Antifúngicos/administração & dosagem , Antifúngicos/farmacologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Géis/química , Óleos/química , Poloxâmero/química , Administração Intravaginal , Animais , Antifúngicos/química , Varredura Diferencial de Calorimetria , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cercopithecus aethiops , Células HeLa , Humanos , Cinética , Testes de Sensibilidade Microbiana , Transição de Fase , Reologia , Temperatura Ambiente , Células Vero , Voriconazol/administração & dosagem , Voriconazol/química , Voriconazol/farmacologia , Difração de Raios X
17.
Mater Sci Eng C Mater Biol Appl ; 99: 591-598, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30889734

RESUMO

Applications of fibrous meshes for localized chemotherapy have been limited by the lack of optimal carriers that are capable of releasing sufficient drug locally. To overcome this obstacle, we introduced Pluronic F127 (PF127) to the camptothecin (CPT)-loaded poly(lactic acid/glycolic acid) (PLGA) electrospun fibrous meshes, abbreviated as PPC, for modulation of drug release. These PPC meshes had smooth surface and high drug loading (5.6-6.8%). Addition of PF127 obviously improved the hydrophilicity of the meshes. Interestingly, the CPT release rate of PPC meshes was significantly higher than that of CPT-loaded PLGA (PLGA-CPT) meshes. Most importantly, incorporation of PF127 in the meshes led to significant reduction in the CT-26 viability compared to PLGA-CPT mesh. The improved anticancer effects of PPC meshes were mainly due to the induction of apoptosis in CT-26 cells. These findings suggest that PPC mesh could be a promising implantable system that may enhance the therapeutic efficacy and prevent tumor recurrence after surgical resection.


Assuntos
Neoplasias do Colo/tratamento farmacológico , Liberação Controlada de Fármacos , Poloxâmero/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Engenharia Tecidual , Adsorção , Animais , Camptotecina/farmacologia , Camptotecina/uso terapêutico , Linhagem Celular Tumoral , Neoplasias do Colo/patologia , Camundongos , Proteínas/química , Temperatura Ambiente , Água/química , Molhabilidade , Difração de Raios X
18.
Drug Dev Ind Pharm ; 45(7): 1130-1139, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30884977

RESUMO

Objective: Control the release and enhance the bioavailability of chitosan-doxazosin mesylate nanoparticles (DM-NPs). Significance: Improve DM bioavailability for the treatment of benign prostatic hyperplasia and hypertension. Methods: Plackett-Burman design was utilized to screen the variables affecting the quality of DM-NPs prepared by ionic gelation method. The investigated variables were initial drug load (X1), chitosan percentage (X2), tripolyphosphate sodium (TPP) percentage (X3), poloxamer percentage (X4), homogenization speed (X5), homogenization time (X6) and TPP addition rate (X7). The prepared DM-loaded NPs have been fully evaluated for particle size (Y1), Zeta potential (Y2), production yield (Y3), entrapment efficiency (Y4), loading capacity (Y5), initial burst (Y6), and cumulative drug release (Y7). Finally, DM pharmacokinetic has been investigated on healthy albino male rabbits by means of non-compartmental analysis. Results: The combination of variables showed variability of Y1, Y2, and Y3 equal to 122-710 nm, 3.49-23.63 mV, and 47.31-92.96%, respectively. While Y4 and Y5, reached 99.87%, and 8.53%, respectively. The prepared NPs revealed that X2, X3, and X4 are the variables that play the important role in controlling the release behavior of DM from the NPs. The in vivo pharmacokinetic results indicated the enhancement in bioavailability of DM by 7 folds compared to drug suspension and the mean residence time prolonged to 23.72 h compared to 4.7 h of drug suspension. Conclusion: The study proved that controlling the release of DM from NPs enhance its bioavailability and improve the compliance of patients with hypertension or benign prostatic hyperplasia.


Assuntos
Quitosana/análogos & derivados , Quitosana/química , Doxazossina/química , Nanopartículas/química , Poloxâmero/química , Polifosfatos/química , Administração Oral , Animais , Disponibilidade Biológica , Química Farmacêutica/métodos , Portadores de Fármacos/química , Liberação Controlada de Fármacos/efeitos dos fármacos , Masculino , Tamanho da Partícula , Coelhos , Suspensões/química
19.
Colloids Surf B Biointerfaces ; 178: 214-221, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30870788

RESUMO

Poloxamer block copolymers (also known as Pluronic®) are particularly useful for drug delivery and self-assembly techniques. These nanopolymers are generally considered to be biologically inert and they were used to generate only bacteria repellent surfaces but keeps bacteria alive and as a latent threat. However, the inherent capabilities of these nanopolymers to kill bacteria have been largely overlooked. Here, we report that Pluronic shaped as superstructures (self-organized array of micelles) in fact possess a broad-spectrum bactericidal activity (capability of killing bacteria) similar to that shown for some antibiotics. This further represents the first report that shows that appropriate control of superstructured mesophase architecture is a key parameter for bactericidal efficacy. Based on this finding, we have developed a highly bactericidal coating (>99.9% kill) against all tested Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative (Salmonella typhimurium LT2, Escherichia coli K12 and Pseudomonas aeruginosa PAO1) bacteria which moreover allows the adhesion and proliferation of mammalian cells. The inexpensiveness and ease of production make these versatile nanopolymer structures a powerful tool for the development of a new generation of highly effective antimicrobial coatings.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Nanoestruturas/química , Poloxâmero/química , Poloxâmero/farmacologia , Bacillus subtilis/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Salmonella typhimurium/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos
20.
Artif Cells Nanomed Biotechnol ; 47(1): 610-621, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30831030

RESUMO

With the purpose of improving the water solubility and oral bioavailability, ursolic acid nanoparticles (UANs) were prepared by the emulsion solvent evaporation method, and the nanosuspension was freeze-dried into powder. The optimal conditions for preparing nanoparticles were screened out using single-factor experiment. Take advantage of the optimal conditions, UA nanoemulsion had mean particle size (MPS) of 69.7 ± 15.6 nm and polydispersity index value (PI) of 0.005. The MPS of UA nanosuspension was gained at 100.2 ± 12.1 nm (PI = 0.005), after the organic solvent was removed by rotary evaporator. Finally, UANs possessing an MPS of 157.5 ± 28.0 nm (PI = 0.005) and zeta potential of 20.33 ± 1.67 mV were obtained after freeze-dried. UANs were investigated using SEM, XRD, DSC, TGA and further explored their equilibrium solubility, dissolution rate, solvent residue analysis, cellular antioxidant activity and oral bioavailability. All the results above showed that UA in UANs was in the amorphous state. The result of solubility test figured that the equilibrium solubility of UANs was 13.48 times in simulated gastric fluid (SGF), 11.79 times in simulated intestinal fluid (SIF) and 23.99 times in deionized water than raw UA. Accordingly, the dissolution rate of UANs in SGF and SIF had an apparent enhancement. The oral bioavailability of UANs increased 2.68 times than raw UA. UANs improved antioxidant activity toward cells compared with raw UA, and EC50 of UANs reduced 37.5 times than raw UA. The residual contents of trichloromethane and ethanol were separated up to the mustard of the ICH limit for class III and class II solvents. The results above indicated that UANs possesses a value of application on enhancement oral bioavailability.


Assuntos
Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/farmacocinética , Solventes/química , Triterpenos/química , Triterpenos/farmacocinética , Administração Oral , Disponibilidade Biológica , Emulsões , Depuradores de Radicais Livres/administração & dosagem , Depuradores de Radicais Livres/farmacologia , Poloxâmero/química , Pressão , Solubilidade , Propriedades de Superfície , Triterpenos/administração & dosagem , Triterpenos/farmacologia , Volatilização , Água/química
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