Flavosomes, novel deformable liposomes for the co-delivery of anti-inflammatory compounds to skin.

Flavosomes, novel deformable liposomes for the topical delivery of anti-inflammatory compounds have been developed and characterized in this study. The carriers were prepared by incorporating flavonoids, specifically quercetin and dihydroquercetin, into transfersome and evaluated as a potential topical delivery system for meloxicam (MX), a potent hydrophobic NSAID (non-steroidal anti-inflammatory drug). Characterization of the flavosomes was conducted in terms of their vesicle size, zeta potential, entrapment efficiency and deformability index. Ex vivo skin permeation and confocal laser scanning microscopy studies demonstrated that the flavosome formulations improved the skin permeation of meloxicam compared to that for transfersomes. The dermal and transdermal delivery of meloxicam using these formulations has the potential of being a promising alternative to conventional oral delivery of non-steroidal anti-inflammatory drugs (NSAIDs) with enhanced local and systemic onset of action and reduced gastrointestinal side effects.

Near-infrared chemical imaging and its correlation with the mechanical properties of chitosan-gelatin edible films.

Plasticizers influence the physical properties of edible films by their interaction with the film-forming polymers. Using near-infrared chemical imaging, it is possible to characterize the interaction between compounds through the analysis of their relative presence throughout the film (abundance) and their variability. These parameters and standard mechanical properties were used to characterize the interaction between gelatin, chitosan and several plasticizers, pure or in binary combinations. Triacetin showed the least interaction with the polymers, while polyethylene glycol 400 and glycerol showed high interaction with them. In addition, we observed that the tensile strength of the film was well correlated with the variability of gelatin and chitosan.

Thermoresponsive block copolymer micelles with tunable pyrrolidone-based polymer cores: structure/property correlations and application as drug carriers.

A-B block copolymer micelles comprised of thermoresponsive hydrophilic PNIPAAm (poly(N-isopropylacrylamide)) coronae and hydrophobic PNP (poly(N-acryloyl-2-pyrrolidone)), PMNP (poly(N-acryloyl-5-methoxy-2-pyrrolidone)), or PBNP (poly(N-acryloyl-5-butoxy-2-pyrrolidone)) cores were examined to identify how systematic adjustments to core-segment structure affect micellar physicochemical properties, drug loading efficiency (DLE), and thermoresponsive drug release among these novel systems. Critical micelle concentrations (CMCs) were found to decrease by two orders of magnitude in the order of PNIPAAm-PNP, PNIPAAm-PMNP, and PNIPAAm-PBNP indicating that minor modifications to the pyrrolidone scaffold significantly affect its hydrophobic character. Moreover, the structural modifications were also found to influence micelle size and intermicellar aggregation that occurs above the lower critical solution temperature (LCST). In line with the CMC data, DLE values of doxorubicin-loaded (i.e., DOX-loaded) micelles increase in the order of PNIPAAm-PNP, PNIPAAm-PMNP, and PNIPAAm-PBNP, a trend attributed to enhanced cohesive forces (i.e. London dispersion forces) between DOX and core as the latter becomes more hydrophobic. When heated above the LCST, DOX release decreases in the order of PNIPAAm-PNP, PNIPAAm-PMNP, and PNIPAAm-PBNP suggesting that release processes are impeded by the cohesive forces responsible for efficient encapsulation. Finally, cytotoxicity assays performed above the LCST reveal that DOX-loaded micelles are as cytotoxic as the free drug in formulations where DOX concentrations are equivalent.

A comparative evaluation of photo-toxic effect of fractionated melanin and chlorpromazine hydrochloride on human (dermal fibroblasts and epidermal keratinocytes) and mouse cell line/s (fibroblast Balb/c 3T3).

Fractionated melanin (Mel-HEV), a bleached version of natural melanin, offers protection against the high energy visible (HEV/UVA) and ultraviolet (specifically UVA) irradiation making it a potential compound to be added to skin care and sunscreen formulations and other cosmetic and personal care products. Chlorpromazine (CPZ) has been shown to exhibit photosensitivity and phototoxicity reaction in vitro and in vivo. Comparative evaluation of chemotoxicity and phototoxicity using Mel-HEV and CPZ (as positive control) was performed on mouse fibroblast cell line 'Balb/c 3T3'. This is the recommended method for evaluating the phototoxic potential of compounds under the European Center of Validation of Alternative Methods (ECVAM) guidelines (OECD, 2004). This study was expanded from a mouse cell line - Balb 3T3/c to two human cell lines - HDF and HEKn for two reasons: to compare the difference between the sensitivity and behavior of two fibroblast cell lines (Balb/c 3T3 vs. HDF) and to compare the differences between two fibroblast cell lines with the keratinocyte cell line (HDF & Balb/c 3T3 vs. HEKn). It was found that Balb/c 3T3 and HEKn were both sensitive to the phototoxic potential of CPZ. However, HDF showed insensitivity to phototoxic evaluation. The test compound, Mel-HEV, was found to be non-phototoxic. The mean toxic concentration (MTC) for CPZ during HEV and UVA exposure conditions was found to be similar using Balb/c 3T3 (36.25 µg/ml) and HEKn (39.99 µg/ml) showing that cells exhibit similar responses at HEV/UVA- conditions. However, Balb/c 3T3 showed more sensitivity to CPZ at HEV/UVA+ condition (MTC=0.87 µg/ml; mean PIF=55.33; MPE=0.395) than HEKn (MTC=5.35 µg/ml; PIF=7.61; MPE=0.276) making it the preferred cell line for phototoxicity evaluations.