OBJECTIVE: Development of oxybutynin chloride (OC) proniosomal gels and analyses of its efficacy for OAB treatment.

MATERIALS AND METHODS: Phase separation coacervation was used to prepare proniosomal gels using various non-ionic surfactants, lipids, soy lecithin and isopropyl alcohol. Gels were characterized with regard to entrapment efficiency (EE), vesicle size, surface morphology (using environmental scanning electron microscopy [E-SEM]), stability, attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, in vitro skin permeation, in vivo animal studies and histopathology.

RESULTS AND DISCUSSION: EE was 87-92%, vesicle size was 0.38-5.0 μm, and morphology showed some loosened pores in proniosomes after hydration. ATR-FTIR spectroscopy showed no significant shifts in peaks corresponding to OC and excipients. Most formulations exhibited >50% permeation but the cholesterol-containing formulations P3 (Span 20:Span 60 [1:1]) and P4 [Tween 20:Tween 80 (1:1)] had the highest percent cumulative permeation. P3 and P4 also showed faster recovery of cholinergic effects on salivary glands than oral formulations. P3 and P4 had pronounced therapeutic effects in reduction of urinary frequency and demonstrated improvements in bladder morphology (highly regenerative surface of the transitional epithelium).

METHODS: Hydrophilic pectin-sulphanilamide films, with or without oleic acid (OA), were subjected to drug release and skin permeation studies. The skins were untreated or microwave-treated, and characterized by infrared spectroscopy, Raman spectroscopy, thermal, electron microscopy and histology techniques.

RESULTS: Skin treatment by microwave at 2450 MHz for 5 min promoted drug permeation from OA-free film without incurring skin damage. Skin treatment by microwave followed by film loaded with drug and OA resulted in permeation of all drug molecules that were released from film. Microwave exerted spacing of lipid architecture of stratum corneum into structureless domains which was unattainable by OA. It allowed OA to permeate stratum corneum and accumulate in dermis at a greater ease, and synergistically inducing lipid/keratin fluidization at hydrophobic C-H and hydrophilic O-H, N-H, C-O, C=O, C-N regimes of skin, and promoting drug permeation.

OBJECTIVES: To develop a novel in vitro skin glycation model as a screening tool for topical formulations with antiglycation properties and to further characterize, at the molecular level, the glycation stress-driven skin ageing mechanism.

METHODS: The glycation model was developed using human reconstituted full-thickness skin; the presence of N(ε) -(carboxymethyl) lysine (CML) was used as evidence of the degree of glycation. Topical application of emulsion containing a well-known antiglycation compound (aminoguanidine) was used to verify the sensitivity and robustness of the model. Cytokine immunoassay, quantitative real-time polymerase chain reaction and histological analysis were further implemented to characterize the molecular mechanisms of skin ageing in the skin glycation model.

RESULTS: Transcriptomic and cytokine profiling analyses in the skin glycation model demonstrated multiple biological changes, including extracellular matrix catabolism, skin barrier function impairment, oxidative stress and subsequently the inflammatory response. Darkness and yellowness of skin tone observed in the in vitro skin glycation model correlated well with the degree of glycation stress.