Lipase-catalyzed construction of glucose-modified brain targeting liposomes with paclitaxel and research on its optimized preparation process / 中草药

Objective: To synthesize brain targeting lipid material [(5-cholesten-3β-yl) (D-glucopyranose-6) sebacate, CHS-SE-GLU] by lipase as catalyst in nonaqueous phase and optimize the preparation technology and formulation of CHS-SE-GLU-modified liposomes. Methods: CHS-SE-GLU was synthesized from CHS-SE prepared in previous work and D-glucose using lipase Novozym 435 in acetone. The structure characterization of the products is obtained by MS and NMR. The CHS-SE-GLU-modified paclitaxel-loaded brain targeting liposomes (GLU-PTX-LP) were prepared by thin film dispersion method. Single factor evaluation was applied to optimizing its preparation technology and formulation. Results: CHS-SE-GLU was confirmed by MS and NMR as target products. The optimal formulation and technology of GLU-PTX-LP were as follows: HSPC as membrane material, the ratio of HSPC to PTX was 0.1, the ratio of CHS to HSPC was 0.5, the dosage of DSPG-Na was 2.5%, hydration time was 0.5 h, and hydration temperature was 50 ℃. Three batches of samples were prepared by optimum preparation process and the average encapsulation efficiency was (93.62±1.34)%, (93.75±1.77)%, (92.04±1.50)%; The average particle size was (89.56±1.35), (92.05±3.42), (104.91±3.71) nm; And the average Zeta potential was (-25.21±0.27), (-26.43±0.44), (-25.17±0.65) mV, respectively. Conclusion: Lipase-catalyzed method for the preparation of brain targeting lipid material is simple and environment friendly with high yield. The entrapment efficiency, particle size, and stability of brain targeting drug-loading liposomes modified by CHS-SE-GLU all meet the requirement, which shows good application prospect.

Lipase-catalyzed synthesis of cholesteryl vinyl hemi-sebacate for selective targeting of liposomes in organic media / 中草药

Objective: To synthesize cholesteryl vinyl hemi-sebacate from cholesterol and divinyl sebacate in non aqueous phase. Methods: TLC, MS, and NMR were used to identify the structure of production; the technological conditions of enzymatic esterification were determined through orthogonal test. Results: The best condition: isooctane 5 mL, reaction temperature 35°C, reaction time 24 h, Candida rugosa Lipase 10 mg/mL, molar ratio of cholesterol to divinyl sebacate 1:6. Conclusion: The highest esterification rate is above 95%.