The aim was to formulate and evaluate Gel/PVA hydrogels as a pH-sensitive matrix to deliver methotrexate (MTX) to colon. The primed Gel/PVA hydrogels were subjected to evaluation for swelling behavior, diffusion coefficient, sol-gel characteristic and porosity using an acidic (pH 1.2) and phosphate buffer (PBS) (pH 6.8 & pH 7.4) media. Fourier transform infrared spectroscopy (FTIR) and thermal gravimetric analysis (TGA) were performed to evaluate the chemical compatibility of the Gel/PVA hydrogel. The shape alteration and release of Gel/PVA hydrogel was conducted at pH 1.2, pH 6.8 and pH 7.4. The drug release kinetic mechanism was determined using various kinetic equations. The physicochemical evaluation tests and drug release profile results were found to be significant (p < 0.01). However, it was dependent on the polymers' concentration, the pH of the release media and the amount of the cross-linking agent. Hydrogels containing the maximum amount of gel showed a dynamic equilibrium of 10.09 ± 0.18 and drug release of 93.75 ± 0.13% at pH 1.2. The kinetic models showed the release of MTX from the Gel/PVA hydrogel was non-Fickian. The results confirmed that the newly formed Gel/PVA hydrogels are potential drug delivery systems for a controlled delivery of MTX to the colon.
The purpose of the present study was to develop emulsions encapsulated by chitosan on the outer surface of a nano droplet containing 5-fluorouracil (5-FU) as a model drug. The emulsions were characterized in terms of size, pH and viscosity and were evaluated for their physicochemical properties such as drug release and skin permeation in vitro. The emulsions containing tween 80 (T80), sodium lauryl sulfate, span 20, and a combination of polyethylene glycol (PEG) and T20 exhibited a release of 88%, 86%, 90% and 92%, respectively. Chitosan-modified emulsions considerably controlled the release of 5-FU compared to a 5-FU solution (p < 0.05). All the formulations enabled transportation of 5-FU through a rat's skin. The combination (T80, PEG) formulation showed a good penetration profile. Different surfactants showed variable degrees of skin drug retention. The ATR-FTIR spectrograms revealed that the emulsions mainly affected the fluidization of lipids and proteins of the stratum corneum (SC) that lead to enhanced drug permeation and retention across the skin. The present study concludes that the emulsions containing a combination of surfactants (Tween) and a co-surfactant (PEG) exhibited the best penetration profile, prevented the premature release of drugs from the nano droplet, enhanced the permeation and the retention of the drug across the skin and had great potential for transdermal drug delivery. Therefore, chitosan-coated 5-FU emulsions represent an excellent possibility to deliver a model drug as a transdermal delivery system.
In this study, a first attempt has been made to deliver levosulpiride transdermally through a thiolated chitosan microneedle patch (TC-MNP). Levosulpiride is slowly and weakly absorbed from the gastrointestinal tract with an oral bioavailability of less than 25% and short half-life of about 6 h. In order to enhance its bioavailability, levosulpiride-loaded thiolated chitosan microneedle patches (LS-TC-MNPs) were fabricated. Firstly, thiolated chitosan was synthesized and characterized by nuclear magnetic resonance (1HNMR) spectroscopy, attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD). Thiolated chitosan has been used in different drug delivery systems; herein, thiolated chitosan has been used for the transdermal delivery of LS. LS-TC-MNPs were fabricated from different concentrations of thiolated chitosan solution. Furthermore, the levosulpiride-loaded thiolated chitosan microneedle patch (LS-TC-MNP) was characterized by FTIR spectroscopic analysis, scanning electron microscopy (SEM) study, penetration ability, tensile strength, moisture content, patch thickness, and elongation test. LS-TC-MNP fabricated with 3% thiolated chitosan solution was found to have the best tensile strength, moisture content, patch thickness, elongation, drug-loading efficiency, and drug content. Thiolated chitosan is biodegradable, nontoxic and has good absorption and swelling in the skin. LS-TC-MNP-3 consists of 100 needles in 10 rows each with 10 needles. The length of each microneedle was 575 μm; they were pyramidal in shape, with sharp pointed ends and a base diameter of 200 µm. The microneedle patch (LS-TC-MNP-3) resulted in-vitro drug release of 65% up to 48 h, ex vivo permeation of 63.6%, with good skin biocompatibility and enhanced in-vivo pharmacokinetics (AUC = 986 µg/mL·h, Cmax = 24.5 µg/mL) as compared to oral LS dispersion (AUC = 3.2 µg/mL·h, Cmax = 0.5 µg/mL). Based on the above results, LS-TC-MNP-3 seems to be a promising strategy for enhancing the bioavailability of levosulpiride.