Preparation and evaluation of ophthalmic thermosensitive in situ gels of penciclovir

Aim To develop pluronic F127 （PF127） based formulations of penciclovir （PCV） aimed at enhancing its ocular bioavailability. Methods Thermosensitive in situ gels of penciclovir were prepared through combination of HPMC K4M or carbopol 934P and pluronic F127. Optimized formulations were examined through measuring gelation temperature, rheology speciality, drug release behavior, pharmacokinetics and ocular irritation. Results The gelation temperature was reduced by adding HPMC K4M or carbopol 934P, and the viscosity was enhanced slightly. Either HPMC K4M or carbopol 934P delayed the release of PCV from in situ gel. PCV was released by non-Fickian diffusion. The study of ocular irritation for different PCV formulations did not show any irritation or damage for the cornea. PCV bioavailability from combination of carbopol 934P and pluronic F127 gels was higher than that obtained from any other gels. Conclusion Pluronic F127 formulations of PCV can be used as liquid for administration by instilling into the eye. Facilitated by the appropriate eye temperature, the formulations were transformed to gel phase. On the basis of in vitro and in vivo results, PCV formulations containing HPMC K4M or carbopol 934P and low concentration of pluronic F127 （12%） showed potential for use as a drug delivery system with improved ocular bioavailability.

A thermosensitive gel formulation of an empirical traditional Chinese prescription for treating cervical erosion

Cervical eropion,a pathological change associated with chronic cervicitis,is a common condition that is difficult to cure.M any pa tients particularly those with mild or medium infection and those preparing for pregnancy require a simple but effective medication.In this study,extracts of an empirical herbal prescription composed of six Chinese traditional drugs viz Cortex Phellodendri,Rhizoma Coptidis,Olibanum,Myrrha,borneol and catechu were formulated to facilitate intravaginal administration and improve efficacy.An extract of the first four components was formulated with borneol as a thermosensitive gel(TG)while an extract of catechu used to prepare a regular gel(CG)because of a chemical incompatibility.The optimized TG was prepared using poloxamer 407 and poloxamer 188.The CG was prepared using glycerin,carbopol and triethanolamine.The gels were characterized in vitro in terms of release of berberine(TG)and total catechins(CG)and in vivo in a rat model of cervical erosion.Trea tment by once daily application of the TG for 7 days followed by once daily application of the CG for 3 days produced a restoration of normal tissues.Gel formulation of the empirical Chinese traditional remedy appears to provide a promising treatment for cervical erosion.

Photoacoustic image-guided corpus cavernosum intratunical injection of adipose stem cell-derived exosomes loaded polydopamine thermosensitive hydrogel for erectile dysfunction treatment

Stem cell-derived exosomes(SC-EXO)was an emerging therapeutic agent in regenerative medicine.Intratunical injection of SC-EXO is considered as a prospective approach for erectile dysfunction(ED)treatment.However,high vascularization of cavernous body makes effective retention a major challenge for SC-EXO intratunical injection.In this study,a Polydopamine nanoparticles(PDNPs)incorporated poly(ethylene glycol)-poly(ε-caprolactone-co-lactide)(PDNPs-PELA)thermosensitive hydrogels were fabricated by a facile in situ polymerization for intratunical administration of adipose stem cell-derived exosomes(EXO).The hydrogels exhibited sol-gel transition at body temperature.Moreover,the in-situ polymerization of PDNPs using poly(ethylene glycol)-poly(ε-caprolactone-co-lactide)(PELA)block copolymer as a template was found to be more stable dispersion in the gel system.After being encapsulated into the hydrogel,EXO shows sustained release behavior within two weeks.In vivo animal experiments revealed that exosomes released from hydrogel lead to the healing of endothelial cells and neurons,increase of the cavity’s pressure,thereby restoring the erectile function.In particular,since the PDNPs in thermosensitive gels have excellent photoacoustic performance,the hydrogel can be accurately delivered into the tunica albuginea by the guidance of real-time photoacoustic imaging.These results suggest that the as-prepared PDNPs-PELA has a promising future as an injectable exosome carrier for ED treatment.