Preparation of mPEG2000-PLA-modified Xingnaojing microemulsion and evaluation in mucosal irritation.

Xingnaojing microemulsion (XNJ-M) administered intranasally is used for stroke treatment. Methoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA) is a block copolymer with surfactant-like properties and good biodegradability and reliable biological safety. In order to investigate the possibility to lower mucosa irritation with XNJ-M, XNJ-M modified by mPEG2000-PLA (XNJ-MM) was prepared. Different ratios of mPEG2000-PLA were synthesized. The structures and properties were confirmed by 1H-NMR, IR, and DSC. The hydrophile-lipophile balance (HLB) value and critical micellar concentration of copolymers were investigated. The in situ toad palate model was adopted to investigate the ciliotoxicity of the copolymers. The XNJ-M and XNJ-MM were prepared by dropping aqueous phase method. Mucosal irritation of different Xingnaojing (XNJ) preparations was studied by behavioral observations including sneezing and scratching nose. The epithelial thickness of nasal mucosa was evaluated and the secretory protein concentration was determined. The results of in situ toad palate model demonstrated that high HLB value mPEG2000-PLA basically showed no ciliotoxicity, while EL-35 had significant dose-dependent ciliotoxicity (P<0.05). The irritating effects of mPEG2000-PLA were significantly lower than EL-35 after seven days of treatment, based on the epithelial thickness of 0.429±0.100 mm and 0.700±0.035 mm, respectively (P<0.01). The epithelial thickness with XNJ-MM was lower than XNJ-M after seven days of treatment: 0.620±0.10 mm vs. 0.809±0.153 mm, respectively (P<0.05). The mPEG2000-PLA-modified microemulsion is a promising dosage form of XNJ, based on reduced irritation on nasal mucosa.