RESUMO
Advanced wound dressings capable of interacting with lesions and changing the wound microenvironment to improve healing are promising to increase the therapeutic efficacy of this class of biomaterials. Aiming at the production of bioactive wound dressings with the ability to control the wound microenvironment, biomaterials of three different chemical compositions, but with the same architecture, were produced and compared. Electrospinning was employed to build up a biomimetic extracellular matrix (ECM) layer consisting of poly(caprolactone) (PCL), 50/50 dl-lactide/glycolide copolymer (PDLG) and poly(l-lactide) (PLLA). As a post-treatment to broaden the bioactivity of the dressings, an alginate coating was applied to sheathe and functionalize the surface of the hydrophobic electrospun wound dressings, in combination with the extract of the plant Arrabidaea chica Verlot, known for its anti-inflammatory and healing promotion properties. Wettable bioactive structures capable to interact with media simulating lesion microenvironments, with tensile strength and elongation at break ranging respectively from 155 to 273â¯MPa and from 0.94 to 1.39% were obtained. In simulated exudative microenvironment, water vapor transmission rate (WVTR) values around 700â¯g/m2/day were observed, while water vapor permeability rates (WVPR) reached about 300â¯g/m2/day. In simulated dehydrated microenvironment, values of WVTR around 200â¯g/m2/day and WVPR around 175â¯g/m2/day were attained.
Assuntos
Bandagens , Materiais Revestidos Biocompatíveis/farmacologia , Fenômenos Mecânicos , Cicatrização , Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Liberação Controlada de Fármacos , Íons , Testes de Sensibilidade Microbiana , Permeabilidade , Extratos Vegetais/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Vapor , Termogravimetria , Fatores de Tempo , Água/química , Difração de Raios XRESUMO
Octacalcium phosphate (OCP) was synthesized yielding a combination of OCP and hydroxyapatite (HA) with a ratio of 90:10 (OCP/HA). A method was developed to functionalize the surface of the apatite using lauroyl chloride to improve the dispersion of the mineral phase in a poly(L-lactide) (PLLA) polymeric matrix. Infrared spectra and thermal gravimetric analysis confirmed the presence of laurate on the surface of calcium phosphate (CaP) particles. Neat HA particles were also functionalized with lauryl chloride for comparative purposes. PLLA/OCP/HA-laurate (PLLA/OCP/HA-L) and PLLA/HA-laurate (PLLA/HA-L) composites were fabricated by electrospinning method. The presence of the functional groups resulted in significant improvement of the dispersion of OCP/HA and HA particles into the polymeric matrix, allowing inclusion of up to 40% of mineral phase. Electrospun fibrous biocomposites of PLLA/CaP containing up to 40% in mineral phase were obtained without compromising their mechanical properties. Measurements of mass loss and calcium release in vitro showed that OCP/HA is more soluble than HA. The bioactivity of the composites was investigated by simulated body fluid test (SBF). Although both PLLA/OCP/HA-L and PLLA/HA-L fibers can form CaP crystals on their surface after exposition in SBF, the results demonstrate a significant enhancement in mineralization when OCP/HA is the mineral phase in the composite instead neat HA. Furthermore, the obtained PLLA/OCP/HA-L electrospun fibers favored the proliferation and differentiation of stem cells from human exfoliated deciduous teeth and mouse calvaria-derived preosteoblastic cells into mineralized osteoblasts. This new material is proposed as fast degrading CaP biocomposite for bone and teeth applications.
Assuntos
Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Fosfatos de Cálcio/química , Diferenciação Celular/efeitos dos fármacos , Poliésteres/química , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Células 3T3 , Animais , Cinética , Camundongos , Camundongos Endogâmicos BALB C , Osteogênese/efeitos dos fármacosRESUMO
In this work, we provide proof-of-concept of formation, physical characteristics and potential use as a drug delivery formulation of Pickering emulsions (PE) obtained by a novel method that combines nanoprecipitation with subsequent spontaneous emulsification process. To this end, pre-formed ultra-small (d.â¼10â¯nm) nanoprecipitated nanoparticles of hydrophobic derivatives of cashew tree gum grafted with polylactide (CGPLAP), were conceived to stabilize Pickering emulsions obtained by spontaneous emulsification. These were also loaded with Amphotericin B (AmB), a drug of low oral bioavailability used in the therapy of neglected diseases such as leishmaniasis. The graft reaction was performed in two CG/PLA molar ratio conditions (1:1 and 1:10). Emulsions were prepared by adding the organic phase (Miglyol 812®) in the aqueous phase (nanoprecipitated CGPLAP), resulting the immediate emulsion formation. The isolation by centrifugation does not destabilize or separate the nanoparticles from oil droplets of the PE emulsion. Emulsions with CGPLAP 1:1 presented unimodal distributions at different CGPLA concentration, lower values in size and PDI and the best stability over time. The AmB was incorporated in the emulsions with a process efficiency of 21-47%, as determined by UV-vis. AmB in CGPLAP emulsions is in less aggregated state than observed in commercial AmB formulation.
Assuntos
Anfotericina B/farmacologia , Anacardium/química , Composição de Medicamentos , Nanopartículas/química , Gomas Vegetais/síntese química , Poliésteres/síntese química , Anfotericina B/química , Precipitação Química , Emulsões/química , Tamanho da Partícula , Gomas Vegetais/química , Espectrofotometria Ultravioleta , Eletricidade EstáticaRESUMO
In this study, poly(L-lactide) (PLA) nanoparticles containing Tamoxifen (Tmx) were developed using an emulsion/solvent evaporation method, observing the influence of surfactants and their concentrations on mean particle size and drug entrapment. Nanoparticles were characterized in terms of size, morphology, polydispersity, interaction drug-polymer and in vitro drug release profile. Cytotoxicity over erythrocytes and tumor cells was assessed. The optimized formulation employed as surfactant 1% polyvinyl alcohol. Mean particle size was 155±4 nm (n=3) and Tmx encapsulation efficiency was 85±8% (n=3). The in vitro release profile revealed a biphasic release pattern diffusion-controlled with approximately 24% of drug released in 24 h followed by a sustained release up to 120 h (30% of Tmx released). PLA nanoparticles containing Tmx presented a very low index of hemolysis (less than 10%), in contrast to free Tmx that was significantly hemolytic. Tmx-loaded PLA nanoparticles showed IC50 value 2-fold higher than free Tmx, but considering the prolonged Tmx release from nanoparticles, cytotoxicity on tumor cells was maintained after nanoencapsulation. Thus, PLA nanoparticles are promising carriers for controlled delivery of Tmx with potential application in cancer treatment.
Assuntos
Nanopartículas/química , Poliésteres/química , Tamoxifeno/química , Portadores de Fármacos , Hemólise/efeitos dos fármacos , Humanos , Tamoxifeno/farmacologiaRESUMO
Poly(L-lactide)/poly(caprolactone triol) (PLLA/PCL-T) membranes were prepared by solution casting in 100/0, 90/10, and 70/30 (w/w) ratios. The membranes were analyzed by dynamic mechanical analysis, differential scanning calorimetry, and mechanical tests. The thermal analysis showed that the 90/10 and 70/30 preparations were partly miscible systems. The glass transition temperature (Tg ) of PLLA decreases as the PCL-T concentration increases, which implies that PCL-T has a plasticizer function. An in vitro study with osteoblastic cells isolated from the calvariae of rats was performed in all preparations. The results obtained in this study showed that the addition of PCL-T to the PLLA matrix modifies its mechanical, thermal, and biological properties. These blends could be useful for tissue engineering for bone applications.
Assuntos
Materiais Biocompatíveis/química , Ácido Láctico/química , Osteoblastos/citologia , Poliésteres/química , Polímeros/química , Animais , Regeneração Óssea , Células Cultivadas , Ratos , Ratos Wistar , Engenharia Tecidual , Temperatura de TransiçãoRESUMO
In this study, poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) and poly(l-lactide) (PLA) microspheres containing ibuprofen were prepared with the aim of prolonging the drug release. The oil-in-water (O/W) emulsion solvent evaporation technique was used, varying the polymer ratio. All formulations provided spherical particles with drug crystals on the surface and a porous and rough polymeric matrix when PHBV was used and smooth external surface when prepared with PLA. The in vitro dissolution profiles show that the formulation containing PHBV/PLA at the proportion of 30/70 presented the best results in terms of prolonging the ibuprofen release. The analysis of the concentration of ibuprofen in the blood of rats showed that maximum levels were achieved at between one and two hours after administration of the immediate-release form (pure drug), while the prolonged microspheres led to a small amount of the drug being released within the first two hours and reached the maximum level after six hours of administration. It was concluded that it is possible to prolong the release of ibuprofen through its incorporation into PHBV/PLA microspheres.
No presente estudo foram preparadas microesferas de poli(hidroxibutirato-co-hidroxivalerato) (PHBV) e poli(ácido láctico) (PLA) com o objetivo de prolongar a liberação do ibuprofeno, utilizado como fármaco modelo. Empregou-se o método de emulsificação e evaporação do solvente óleo em água (O/A), variando-se a proporção entre os polímeros. Todas as formulações originaram partículas esféricas com cristais de fármaco aderidos à superfície externa. As microesferas apresentaram superfície rugosa e porosa, quando o PHBV foi utilizado, e superfície externa lisa, quando preparadas com o PLA. Os perfis de dissolução in vitro evidenciaram que a formulação que continha PHBV/PLA na proporção de 30/70 apresentou melhores resultados para prolongar a liberação do ibuprofeno. Através da análise da concentração de ibuprofeno no plasma de ratos, após administração oral, verificou-se que os níveis máximos ocorreram entre 1 e 2 horas após a administração de ibuprofeno não encapsulado, enquanto o fármaco presente nas microesferas atingiu um pico máximo após 6 horas da administração. Conclui-se, portanto, que é possível prolongar a liberação do ibuprofeno após a sua incorporação às microesferas preparadas com os polímeros PHBV e PLA, especialmente na proporção de 30/70.