Upregulated Guanine Deaminase Is Involved in Hyperpigmentation of Seborrheic Keratosis via Uric Acid Release

Seborrheic keratosis, which is a benign tumor composed of epidermal keratinocytes, develops common in the elderly. Uric acid generated by upregulated guanine deaminase (GDA) has been identified to cause UV-induced keratinocyte senescence in seborrheic keratosis. Seborrheic keratosis is also frequently pigmented. Growing evidences indicate that hyperuricemia is a risk factor of acanthosis nigricans, an acquired skin hyperpigmentation. The objective of this study was to investigate role of GDA and its metabolic end product, uric acid, in hyperpigmentation of patients with seborrheic keratosis using their lesional and non-lesional skin specimen sets and cultured primary human epidermal keratinocytes with or without GDA overexpression or uric acid treatment. GDA-overexpressing keratinocytes or their conditioned media containing uric acid increased expression levels of MITF and tyrosinase in melanocytes. Uric acid released from keratinocytes was facilitated by ABCG2 transporter with the help of PDZK1 interaction. Released uric acid was taken by URAT1 transporter in melanocytes, stimulating melanogenesis through p38 MAPK activation. Overall, GDA upregulation in seborrheic keratosis plays a role in melanogenesis via its metabolic end product uric acid, suggesting that seborrheic keratosis as an example of hyperpigmentation associated with photoaging.

"FORMULATION AND EVALUATION OF MORONIC ACID LOADED TRANSDERMAL PATCHES"

Objective: To prepare Transdermal patches of Moronic acid along with various polymers for controlled release action. Methods: Suitable method such as Solvent Casting Technique of Film Casting Technique are used for the preparation of Transdermal patch. Results: The prepared Transdermal patches were transparent, smooth, uniform and flexible. The method adopted for the preparation of the system was found satisfactory. Conclusion: Various formulations were developed by using hydrophilic and hydrophobic polymers like HPMC E5 and EC respectively in single and combinations by solvent evaporation technique with the incorporation of penetration enhancer such as dimethylsulfoxide and dibutyl phthalate as plasticizer. Formulation F7 containing an equal ratio of HPMC E5: EC (5:5) showed maximum and sustained release of 86.814±0.262 within 24 h. Kinetic models were used to confirm the release mechanism of the formulations. Moronic acid release from the patches F1 to F7 followed non Fickian diffusion rate controlled mechanism.

Enhanced Mefenamic Acid Release from Poloxamer-Silicon Dioxide Gel Filled in Hard Gelatin Capsules – An application of Liquid Semisolid Matrix Technology for Insoluble Drug

Introduction: : Liquid semisolid matrix (LSSM) technology involves the filling of drug-mixed gel in hard gelatin capsules for different applications. Methods: In continuation of our previous work on LSSM technology, 10% (w/w) of practically insoluble model drug, mefenamic acid was incorporated in gels of different poloxamers with 8% (w/w) SiO2. Gels exhibited plasticity or pseudoplasticity along thixotropy at 2 and 24 h enabling their easy filling into hard gelatin capsules without content seepage. Mefenamic acid gels prepared with L64 and L92 maintained their apparent viscosities for the study period of one month. Around 100% mefenamic acid was released within 90 min from L64- and in 150 min from L92-SiO2 gels, both with first-order kinetics. Results: In 12 month long-term stability studies, only mefenamic acid-L64-SiO gel at 30°C/65% RH indicated dispersion stability with similar rheology and release pattern to that at 2, 24 and 30 days. Conclusion: No chemical drug-polymer interactions were found in FTIR. The release of practically insoluble mefenamic acid could be enhanced from gel formulated with L64 and SiO2.

Sinapic Acid Release at the Cell Level by Incorporation into Nanoparticles: Experimental Evidence Using Biomembrane Models

Sinapic acid (SA), belonging to the phenylpropanoid family, and its derivatives are secondary metabolites found in the plant kingdom. In recent years, they have drawn attention because of their various biological activities, including neuroprotective effects. In this study, SA was incorporated into two different nanoparticle systems, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC). The influence of different concentrations of SA on the nanoparticle systems was evaluated. It was studied the efficacy of the nanoparticle systems to release the active ingredient at cell level through the use of models of biological membranes represented by multilamellar vesicles (MLV) of dimyristoylphosphatidylcholine (DMPC) and conducting kinetic studies by placing in contact SLN and NLC, both unloaded and loaded with two different amounts of SA, with the same biological membrane model. Differential scanning calorimetry (DSC) was used for these studies. The results indicated a different distribution of SA within the two nanoparticle systems and that NLC are able to incorporate and release SA inside the structure of the biological membrane model.