CD226 gene polymorphism (rs763361 C>T) is associated with susceptibility to type 1 diabetes mellitus among Egyptian children.

OBJECTIVE: Genetic factors contribute significantly to type 1 diabetes (T1D) etiology. A single nucleotide polymorphism in the CD226 gene (rs763361 C>T) has been associated with T1D susceptibility in European patients, but data from other populations is limited. Our aim was to study the contribution of this polymorphism to T1D susceptibility among Egyptian children. METHODS: A case-control study including 74 children with T1D and 82 healthy children as a control group. Genotyping of CD226 gene polymorphism was performed for all participants by DNA extraction followed by polymerase chain reaction and restriction fragment length polymorphism. RESULTS: The frequency of T allele was 78.4% in patients and 68.3% in controls (OR, 1.68; 95% CI, 1.01-2.8; P=0.046). TT, TC, and CC genotypes were found in 62.2%, 32.4%, and 5.4% of the patients, respectively, and in 41.5%, 53.7%, and 4.9% of controls, respectively. Under the recessive model, TT genotype was significantly associated with T1D risk (OR, 2.32; 95% CI, 1.21-4.41; P=0.010). The mean age at diabetes onset was significantly lower in patients carrying T allele compared with C allele (8.03±3.8 year vs. 10.5±2.54 year; P<0.001) and among those with TT genotype compared with the pooled TC+CC genotypes (7.5±2.6 year vs. 10.6±2.6 year; P<0.001). No significant difference was found between genotypes or alleles regarding the HbA1c level. CONCLUSION: T allele and TT genotype of the CD226 rs763361 polymorphism is associated with susceptibility to T1D and with a lower age of disease onset among Egyptian children.

Physically cross-linked polyvinyl alcohol for the topical delivery of fluconazole.

The aim of this study was to develop fluconazole in an ultrapure polyvinyl alcohol (PVA) hydrogel able to deliver the drug in a sustained release pattern for local treatment of skin fungal infections. The topical fluconazole hydrogels were prepared using PVA hydrogels physically cross-linked by freeze-thaw technique. Polyethylene glycol (PEG) was added as a hydrophilic excipient as a release enhancer of fluconazole. The effects of PVA molecular weight, PEG molecular weight, and PEG concentration were studied using a 2 x 4 x 2 factorially designed experiment. The selected fluconazole hydrogel proved to be physically stable over a period of 6 months and to be effective in the topical treatment of cutaneous candidiasis. Therefore, it could be concluded that the formula composed of 10% PVA 205000 and 1.5% PEG 4000 and 2% fluconazole and prepared by three cycles of freezing, and thawing is very promising in the local treatment of skin fungal infection as an alternative to the systemic use of fluconazole.

Lipospheres as carriers for topical delivery of aceclofenac: preparation, characterization and in vivo evaluation.

The purpose of this study was to prepare lipospheres containing aceclofenac intended for topical skin delivery with the aim of exploiting the favorable properties of this carrier system and developing a sustained release formula to overcome the side effects resulting from aceclofenac oral administration. Lipospheres were prepared using different lipid cores and phospholipid coats adopting melt and solvent techniques. Characterization was carried out through photomicroscopy, scanning electron microscopy, particle size analysis, DSC, In vitro drug release and storage study. The anti-inflammatory effect of liposphere systems was assessed by the rat paw edema technique and compared to the marketed product. Results revealed that liposphere systems were able to entrap aceclofenac at very high levels (93.1%). The particle size of liposphere systems was well suited for topical drug delivery. DSC revealed the molecular dispersion of aceclofenac when incorporated in lipospheres. Both entrapment efficiency and release were affected by the technique of preparation, core and coat types, core to coat ratio and drug loading. Lipospheres were very stable after 3 months storage at 2-8 degrees C manifested by low leakage rate (less than 7%) and no major changes in particle size. Finally, liposphere systems were found to possess superior anti-inflammatory activity compared to the marketed product in both lotion and paste consistencies. Liposphere systems proved to be a promising topical system for the delivery of aceclofenac as they possessed the ability to entrap the drug at very high levels and high stability, and to sustain the anti-inflammatory effect of the drug.

Formulation of an antispasmodic drug as a topical local anesthetic.

Mebeverine hydrochloride, a spasmolytic agent on GIT smooth muscles, was reported to have a local anesthetic effect. Thus, it was desired in this study to formulate mebeverine HCl into a gel that could be used locally in the treatment of different oral painful conditions. Poloxamer 407 (P-407) was used as the base for this gel. Different additives were used to enhance drug release from the preparation while others were used to enhance the residence time for the preparation. Different formulae were characterized in terms of drug release and mucoadhesion. The formula which has shown the best compromise between the aforementioned parameters was selected for clinical evaluation in comparison to Lidocaine HCl gel and rheologically examined. The best drug release enhancer was cetrimide (0.005%, w/w), while hydroxypropylcellulose (0.5%, w/w) as a mucoadhesive additive has shown the best compromise between fast drug release and mucoadhesion. The gel formula (G) has shown a better pain reduction efficiency (p=0.0078) and longer duration (p=0.0313) than Lidocaine HCl gel. Histopathological examination has shown no change in the inflammatory cells count of rat oral mucosa. Therefore, it could be concluded that (G) is very promising as a local anesthetic preparation for the treatment of different oral painful conditions.