Novel mixed polymeric micelles formed by biocompatible polymers,mPEG-PLA and Pluronic P105,were fabricated and used as a nanocarrier to solubilize the poorly soluble anesthetic drug propofol.Propofol was added directly to an aqueous solution of mPEG-PLA/Pluronic P105 mixed micelles and stirred into a micellar solution.The average particle size and size distribution of micelles were evaluated by the dynamic light scattering technology.Drug loading content,encapsulation efficiency and free drug concentration were determined by using ultracentrifugation and lyophilization.In vitro release characteristic of propofol formulation was investigated by dialysis method.The physical stability of mixed micelles was also assessed under storage condition（4 oC） after six months.Sleep-recovery studies in male Sprague-Dawley rats,at a dose of 10 mg/kg were performed to compare the pharmacodynamic profiles of propofol in mixed micelles with that of commercial lipid emulsion（CLE）.The results indicated that solubilization of propofol in the mixed micelles was more efficient than that in mPEG-PLA alone.Micelles with the optimized composition of mPEG-PLA/Pluronic P105/Propofol（10：4：5,w/w/w） had particle size of about 90 nm with narrow distribution（polydispersity index of about 0.2）.The content of free propofol in the aqueous phase of mixed micelles was significantly lower than that in CLE（P〈0.05）.There was no remarkable differences for particle size,polydispersity index,and free drug concentration when the mix micelles were stored at 4 oC for six months,suggesting that the propofol-loaded mixed micelles were stable for at least six months.The accumulative release of mixed micelles was significantly higher than that of CLE at the corresponding time points,suggesting that quick release rate for mixed micelles might produce favorable pharmacological effect.No significant differences in the unconsciousness time and recovery time of righting reflex were observed between the mixed micelles and CLE（P〉0.05）.In
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.
