Hyaluronic Acid-Coated Chitosan/Gelatin Nanoparticles as a New Strategy for Topical Delivery of Metformin in Melanoma.

Metformin is a multipotential compound for treating diabetes II and controlling hormonal acne and skin cancer. This study was designed to enhance metformin skin penetration in melanoma using nanoparticles containing biocompatible polymers. Formulations with various concentrations of chitosan, hyaluronic acid, and sodium tripolyphosphate were fabricated using an ionic gelation technique tailored by the Box-Behnken design. The optimal formulation was selected based on the smallest particle size and the highest entrapment efficiency (EE%) and used in ex vivo skin penetration study. In vitro antiproliferation activity and apoptotic effects of formulations were evaluated using MTT and flow cytometric assays, respectively. The optimized formulation had an average size, zeta potential, EE%, and polydispersity index of 329 ± 6.30 nm, 21.94 ± 0.05 mV, 64.71 ± 6.12%, and 0.272 ± 0.010, respectively. The release profile of the optimized formulation displayed a biphasic trend, characterized by an early burst release, continued by a slow and sustained release compared to free metformin. The ex vivo skin absorption exhibited 1142.5 ± 156.3 µg/cm2 of metformin deposited in the skin layers for the optimized formulation compared to 603.2 ± 93.1 µg/cm2 for the free metformin. Differential scanning calorimetry confirmed the deformation of the drug from the crystal structure to an amorphous state. The attenuated total reflection Fourier transform infrared results approved no chemical interaction between the drug and other ingredients of the formulations. According to the MTT assay, metformin in nanoformulation exhibited a higher cytotoxic effect against melanoma cancer cells than free metformin (IC50: 3.94 ± 0.57 mM vs. 7.63 ± 0.26 mM, respectively, P < 0.001). The results proved that the optimized formulation of metformin could efficiently decrease cell proliferation by promoting apoptosis, thus providing a promising strategy for melanoma therapy.

Wound Healing Properties of Pelargonium Graveolens L'Hér Extract Lipogel: In-Vivo Evaluation in an Animal Burn Model.

BACKGROUND: Pelargonium graveolens L'Hér has traditionally been used to reduce skin inflammation, and recent studies have confirmed antioxidant compounds in the plant's extract. The present study aimed to prepare a lipogel formulation from P. graveolens hydroalcoholic extract and evaluate its efficacy on the wound healing process in an animal model. MATERIAL AND METHODS: The aerial part extract of P. graveolens was prepared through percolation. Additionally, plastibase was prepared by mixing 5% of low-molecular-weight polyethylene with hot mineral oil (130°C). The extract (5%) was levigated in the mineral oil (5-15%) and dispersed in the cooled plastibase. The physical properties of the lipogel, thermal stability, and microbial limits were tested. Further, the effect of the lipogel in the wound healing rate was examined among male Wistar rats, and skin tissue samples were assessed histologically. RESULTS AND DISCUSSION: The results represented the best rheological and thermal stability characteristics in the formulation with 5% mineral oil (as the levigator). The lipogel-treated group had the least burn area compared to the silver sulfadiazine and negative control groups (p<0.05). The microscopic examination of tissue samples revealed increased collagen fiber production and maturation and significantly also faster epithelial repair among lipogel-treated rats than in the other two groups(p<0.05). CONCLUSION: The results indicated the significant therapeutic effects of P. graveolens lipogelon burn healing. The suitable physicochemical properties and the low lipogel production cost facilitate further scale-up studies.

Solid Dispersion Pellets: An Efficient Pharmaceutical Approach to Enrich the Solubility and Dissolution Rate of Deferasirox.

Deferasirox (DFX) is an oral iron-chelating agent and classified into class II of the Biopharmaceutics Classification System. Low bioavailability of the drug due to insufficient solubility in physiological fluids is the main drawback of DFX. The idea of the current study was to explore the potential of solid dispersion (SD) as an effective method to improve the dissolution rate of DFX in pellets. The SDs were made by the solvent evaporation technique using polyethylene glycol 4000 (PEG 4000) and polyvinylpyrrolidone K25 with different drug-to-carrier ratios. Then, the dispersion was milled and mixed with other components and the mixture layered on sugar-based cores by pan coating technique. The pellets were evaluated in terms of size distribution, morphology (SEM), and dissolution behaviour. Drug-polymer interactions were studied using differential scanning calorimetry (DSC), X-ray diffraction study (XRD), and Fourier transformation infrared (FTIR) spectroscopy. The pellets coated with SD showed a remarkable rise in the solubility of DFX than that of free drug-loaded pellets. The dispersion with PVP K25 showed a faster dissolution rate as compared to other mixtures. The DSC and XRD analysis indicated that the drug was in the amorphous state when dispersed in the polymer. The FTIR studies demonstrated any ruled out interaction between drug and polymer. The SEM showed smoothness on the surface of the pellets. It is resolved that the SD method considerably enriched the dissolution rate of DFX in pellets, which can also be utilized for other poorly water-soluble drugs.