Ectoine gel transdermal formulation as a novel therapeutic approach in melanoma using 3D printed microneedles.

A 7%w/w ectoine formula, from natural source, is formulated to reduce melanomagenesis, enhance penetration by 3D printed microneedles (MNs), with specified length, diameter and tip to ensure painless effect. Ectoine gel formulations were prepared using Carbopol 940 and Pluronic (F127). The effect of the polymers on pH, viscosity, spreadability, and the in vitro, ex vivo release profiles was obtained. The physiochemical investigation showed uniform gel formulations. The formulations' in vitro and ex vivo drug release displayed a controllable drug release pattern, reaching 63.7-96% and 73-94.7% after 24 h. The permeation study of the in vitro and ex vivo release revealed that the drug release from gels followed diffusion mechanism. The selected formula was used, 3D printed MN array was applied to treat melanoma. Male rats were used for induction of melanoma using 0.5% of 7,12-dimethylbenz[a]anthracene three times weekly for 12 weeks, histopathology was applied to ensure development of carcinoma then rats were treated using the selected formula. Following treatment for continuous 6 weeks, histopathology showed a change in anatomy of skin, which started to return to its normal structure. The anti-melanogenesis activity of optimum formula of ectoine gel, enhanced by 3D printed MN, was found to be effective in reducing the severity of skin cancer reinforcing the efficacy of the promising treatment.

Synthesis and characterization of new functionalized chitosan and its antimicrobial and in-vitro release behavior from topical gel.

Recently, chitosan and its derivatives have been gaining more attention due to their high integration into various biomedical applications. Herein, a new chitosan derivative was prepared by linking the chitosan (Cs) with a novel heterocyclic compound, Benzoimidazolyl-thiadiazole (BzimTD) to form Cs-BzimTD. The synthesis of the new chitosan derivative was confirmed by Fourier-Transform Infrared (FT-IR) spectroscopy, proton nuclear magnetic resonance (1H NMR), thermogravimetric (TGA-DTG) analysis, elemental analysis, and UV-Visible spectrophotometer. Data showed the high efficacy of functionalized Cs-BzimTD to inhibit the growth of pathogenic microbes, Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans, with inhibition zones of 15.3 ± 0.6 - 9.2 ± 0.3 mm. Also, Cs-BzimTD was applied in a topical gel formulation by using two different polymers, Carbopol 940 (CP) and Carboxymethyl Cellulose (CMC) to form three gel formulations: Cs-BzimTD-CP, Cs-BzimTD-CMC, and Cs-BzimTD-CP-CMC. The new gels were checked for physical appearance, viscosity, Cs-BzimTD release, pH, spread-ability, and drug content. The results showed that all formulations were clear, transparent, and homogeneous with non-irritant pH values for skin (6.4 - 6.8). The spread-ability was found in the range of 7.1 - 9.4 g.cm/s. The Cs-BzimTD-CP formula showed the maximal Cs-BzimTD content percentage (86.5%) and the Cs-BzimTD release varied from 89.9 to 81.6% after 8 h depending on the gel formulation, with a maximum release achieved for Cs-BzimTD-CMC.

Application of Optimization Technique to Develop Nano-Based Carrier of Nigella Sativa Essential Oil: Characterization and Assessment.

BACKGROUND: Chitosan, a naturally occurring polymer, has interesting applications in the field of drug delivery due to its plentiful advantages as biodegradability, biocompatibility and nontoxic nature. Nigella sativa essential oil is unstable, volatile, and insoluble in water and these problems confine its usage in developing new medicines. OBJECTIVE: This study focuses on developing a chitosan-based nanocarrier for the encapsulation of Nigella Sativa essential oil. By using Quality by design outline, the quality target product outline, critical quality attributes and critical material attributes were defined by knowledge and risk-based procedures. METHODS: According to defined critical material attributes, Optimization software (Statgraphics XVII) was used to study the effect of the processing parameters. The processing parameters identified and fixed first with a "One factor at a time" approach. Various physicochemical characterization techniques were performed. RESULTS: As a result, the ratio of chitosan to benzoic acid (2:1) along with the stirring rate (4000 rpm) produced minimum-sized particles (341 nm) with good stability. The anti-bacterial activity study using Staph. Aureus strain proved that the optimized nanoparticles were more efficacious than the pure oil based on the diameter of inhibition zone obtained (diameter =5.5 cm for optimized formula vs diameter = 3.6 cm for pure oil). Furthermore, MTT (methyl thiazolyl-diphenyl-tetrazolium bromide) assay was performed to compare the in vitro cytotoxicity using two different cell lines (i.e. HCT 116 for colorectal carcinoma and PC3 for prostatic cancer). It was found that in both cell lines, the optimized nanoparticles had noteworthy antiproliferative properties illustrated by determining the concentration at which 50% of growth is inhibited (IC50). The optimized nanoparticles showed lower IC50 (17.95 ±0.82 and 4.02 ±0.12µg/ml) than the bare oil IC50 (43.56 ±1.95 and 29.72 ±1.41µg/ml).