ABSTRACT
Chitosan-poly(vinyl alcohol) hydrogels can be produced by the freeze-thawing method without using toxic crosslinking agents. The applications of these systems are limited by their characteristics (e.g., porosity, flexibility, swelling capacity, drug loading and drug release capacity), which depend on the freezing conditions and the kind and ratio of polymers. This protocol describes how to prepare hydrogels from chitosan and poly(vinyl alcohol) at 50/50 w/w % of polymer composition and varying the freezing temperature (-4 °C, -20 °C, -80 °C) and freeze-thawing cycles (4, 5, 6 freezing cycles). FT-IR spectra, SEM micrograph and porosimetry data of hydrogels were obtained. Also, the swelling capacity and drug loading and release of diflunisal were assessed. Results from SEM micrographs and porosimetry show that the pore size decreases, while the porosity increases at lower temperatures. The swelling percentage was higher at the minor freezing temperature. The release of diflunisal from the hydrogels has been studied. All the networks maintain the drug release for 30 h and it has been observed that a simple diffusion mechanism regulates the diflunisal release according to Korsmeyer-Peppas and Higuchi models.
Subject(s)
Chitosan/chemistry , Hydrogels/chemistry , Polyvinyl Alcohol/chemistry , Diflunisal/pharmacology , FreezingABSTRACT
Engineering of multifunctional drug nanocarriers combining stability and good release properties remains a great challenge. In this work, natural polymers κ-carrageenan (κ-CAR) and chitosan (CS) were deposited onto olive oil nanoemulsion droplets (NE) via layer-by-layer (LbL) self-assembly to study the release mechanisms of the anti-inflammatory diflunisal (DF) as a lipophilic drug model. The nano-systems were characterized by dynamic light scattering (DLS), zeta potential (ζ-potential) measurements, transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray energy dispersive spectroscopy (XEDS) and Fourier transform infrared spectroscopy (FTIR) to confirm the NE-coating with polymer layers. In addition, kinetic release studies of DF were developed by the dialysis diffusion bag technique. Mathematical models were applied to investigate the release mechanisms. The results showed that stable and suitably sized nanocapsules (~300 nm) were formed. Also, the consecutive adsorption of polyelectrolytes by charge reversal was evidenced. More interestingly, the drug release mechanism varied depending on the number of layers deposited. The nanosized systems containing up to two layers showed anomalous transport and first order kinetics. Formulations with three and four layers exhibited Case II transport releasing diflunisal with zero order kinetics. Hence, our results suggest that these polyelectrolyte nanocapsules have great potential as a multifunctional nanocarrier for drug delivery applications.
ABSTRACT
Poly(beta-malic acid) hydrophobic derivatives are promising polymers for biomedical and pharmaceutical applications. The objectives of the present work were to study the in vitro degradation profile of three PMLA hydrophobic derivatives and to evaluate their cytotoxicity before and after degradation. For this purpose, nanoparticles from poly(benzyl-malate) (PMLABe), poly(hexyl-malate) (PMLAHe), and poly(malic acid-co-benzyl-malate) (PMLAH/He) were prepared for degradation studies on standardized materials. Size exclusion chromatography (SEC) and 1H NMR indicated that degradation occurred by random hydrolysis of the polymer main chain for all three polymer derivatives. The presence of carboxyl groups on the side chain and their esterification with different alcohols varying hydrophilicities could affect the degradation rate. It was postulated that the degradation depended on the rate of diffusion of water into the core of the particles. The cytotoxicity of the polymer nanospheres as well as their degradation products were evaluated in vitro with J774 A1 murine macrophage-like cell line. The cytotoxicity depended on the degradation rate of the polymers and the amount of degradation products of low molecular weight produced.
