10-Hydroxy Decanoic Acid-Based Vesicles as a Novel Topical Delivery System: Would It Be a Better Platform Than Conventional Oleic Acid Ufasomes for Skin Cancer Treatment?

10-hydroxy decanoic acid (HDA), a naturally derived fatty acid, was used for the preparation of novel fatty acid vesicles for comparison with oleic acid (OA) ufasomes. The vesicles were loaded with magnolol (Mag), a potential natural drug for skin cancer. Different formulations were prepared using the thin film hydration method and were statistically evaluated according to a Box-Behnken design in terms of particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE). The ex vivo skin permeation and deposition were assessed for Mag skin delivery. In vivo, an assessment of the optimized formulae using 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin cancer in mice was also conducted. The PS and ZP of the optimized OA vesicles were 358.9 ± 3.2 nm and -82.50 ± 7.13 mV compared to 191.9 ± 6.28 nm and -59.60 ± 3.07 mV for HDA vesicles, respectively. The EE was high (>78%) for both types of vesicles. Ex vivo permeation studies revealed enhanced Mag permeation from all optimized formulations compared to a drug suspension. Skin deposition demonstrated that HDA-based vesicles provided the highest drug retention. In vivo, studies confirmed the superiority of HDA-based formulations in attenuating DMBA-induced skin cancer during treatment and prophylactic studies.

Intranasally administered in situ gelling nanocomposite system of dimenhydrinate: preparation, characterization and pharmacodynamic applicability in chemotherapy induced emesis model.

The aim of the current manuscript was to test the applicability of a nanocomposite system of penetration enhancer vesicles (PEVs) within polymeric in situ forming gel network composed of poloxamer and hyaluronic acid for the intranasal delivery of the antiemetic dimenhydrinate (DMH). PEVs were prepared using phospholipids and labrasol/transcutol/PEG 400 as penetration enhancers, and characterized for entrapment efficiency (EE%), particle size, zeta potential and morphology. The nanocomposite in situ forming gel system was characterized for its sol-gel temperature, viscosity and mucoadhesiveness, and was pharmacodynamically tested on a cisplatin induced emesis model in rats in terms of food, water, kaolin intake and stomach weight content. The selected PEVs formula displayed EE% of 83% for DMH, particle size of 121 nm and a surface charge of 0.83 mV. The selected nanocomposite in situ gelling formula showed a viscosity of 2.13 Pa.S, mucoadhesive force of 0.62 N and DMH controlled release over 6 hours. The pharmacodynamic study showed the superiority of the nanocomposite in situ gelling formula; being administered at a lower dose than the oral marketed formula. The described nanocomposite system proved to be successful for the intranasal delivery of DMH, thus presenting a promising delivery modality for similar antiemetics.

Comparative pharmaceutical study on colon targeted micro-particles of celecoxib: in-vitro-in-vivo evaluation.

In order to target celecoxib which is a COX2 inhibitor, with potentials in the prevention and treatment of colitis and colon cancer, it was formulated as microparticles using the solvent/evaporation method and various pH-dependent Eudragit polymers. The in-vitro evaluation of the prepared microparticles showed spherical and smooth morphology. The encapsulation efficiency and yield were high, indicating that the method used is simple and efficient at this scale. The in-vitro release study showed no release in the acidic medium for 2 h followed by the release of the drug in pH 6.8 in case of Eudragit L100-55 and L100 and pH 7.4 in case of Eudragit S100. The pharmacokinetic parameters were calculated and method validation was performed to insure that it is suitable and reliable. Pharmacokinetic parameters were investigated by determining the Cmax, Tmax, AUC0-t, Kel, and t1/2 of the drug as a suspension and as microparticles. There was a significant difference (p < 0.05) in Tmax between the drug as a suspension and as microparticles. The effect of celecoxib on the degree of inflammation was examined on acetic acid induced colitis rat model and the drug was given as a suspension and as microparticles. The evaluation was done using macroscopical, microscopical and biochemical examination. There was a significant difference between the acetic acid control group and the treatment groups regarding all examination criteria in the order microparticles formulated using Eudragit S100 followed by Eudragit L100-55 while microparticles using Eudragit L100 and drug suspension showed almost the same results.

The clinical efficacy of cosmeceutical application of liquid crystalline nanostructured dispersions of alpha lipoic acid as anti-wrinkle.

Topical 5% alpha lipoic acid (ALA) has shown efficacy in treatment of photo-damaged skin. The aim of this work was to evaluate the potential of poloxamer (P407) gel as a vehicle for the novel lipid base particulate system (cubosome dispersions) of ALA. Cubosome dispersions were formulated by two different approaches, emulsification of glyceryl monoolein (GMO) and poloxamer (P407) in water followed by ultrasonication, and the dilution method using a hydrotrope. Three different concentrations of GMO were used to formulate the cubosome dispersions using the first method, 5% (D1), 10% (D2) and 15% w/w (D3). In the second technique an isotropic liquid was produced by combining GMO with ethanol, and this isotropic liquid was then diluted with a P407 solution (D4). The dispersions were characterized by zeta potential, light scattering techniques, optical and transmission electron microscopy, encapsulation efficiency and in vitro drug release. Results showed that D4 was not a uniform dispersion and that D1, D2 and D3 were uniform dispersions, in which by increasing the GMO content in the dispersion, the size of the cubosomes decreased, zeta potential became more negative, encapsulation efficiency increased up to 86.48% and the drug release rate was slower. P407 gels were prepared using the cold method. Two concentrations of P407 gel were fabricated, 20 and 30% w/w. P407 gels were loaded with either ALA or dispersions containing ALA cubosomes. P407 gels were characterized by critical gelation temperature, rheological measurements and in vitro drug release studies. Results suggested that by increasing P407 concentration, the gelation temperature decreases and viscosity increases. Drug release in both cases was found to follow the Higuchi square root model. Gel loaded with ALA cubosomes provided a significantly lower release rate than the gel loaded with the un-encapsulated ALA. A double blinded placebo controlled clinical study was conducted, aiming to evaluate the efficacy as an anti-wrinkle agent and volunteer's satisfaction upon application of topical 30% P407 gel loaded with ALA cubosomes. Results indicated reduction in facial lines, almost complete resolution of fine lines in the periorbital region and upper lip area and overall improvement in skin color and texture in most volunteers. There were no instances of irritation, peeling or other apparent adverse side effects.