Improved gastrointestinal stability of solid lipid nanoparticles using comb-shaped amphiphilic inulin derivatives.

In order to reduce enzymatic degradation and thereby enhance the stability of solid lipid nanoparticles (SLNs) in the gastrointestinal tract, comb-shaped amphiphilic macromolecular material (CAM) of dodecyl inulin (Inu12) and octadecyl inulin (Inu18) were designed as the emulsifier and stabilizer to modify SLNs (Inu12/Inu18-SLNs). Inu12-SLNs and Inu18-SLNs had similar particle size as the control SLNs (P188-SLNs and Tween-SLNs) prepared with the straight chain surfactants, poloxamer 188 and tween-80 as the emulsifier, which ranged from 220 nm to 270 nm. The zeta potentials of all the SLNs formulations were slightly negative. Cyclosporine A (CsA)-loaded Inu12-SLNs and Inu18-SLNs showed a much lower drug release than CsA-loaded Tween-SLNs at pH 6.8 PBS containing 0.1% sodium dodecylsulfate and all the three SLNs exhibited biphasic release profiles. The results of cytotoxicity test showed that the toxic effects of Inu12-SLNs and Inu18-SLNs on cell viability had no significant difference in comparison to P188-SLNs and Tween-SLNs. Both CAM-modified SLNs (Inu12/Inu18-SLNs) showed a significant reduced lipolysis in vitro. As compared to P188-SLNs and Tween-SLNs, the total lipolysis of Inu18-SLNs during 4 h was decreased by 31.51 % and 45.67 % and that of Inu12-SLNs was decreased by 24.13 % and 38.29 %, respectively. Besides, the cumulative drug precipitations for CsA-loaded Inu12-SLNs and Inu18-SLNs during 4 h lipolysis were dramatically declined, which were 64% and 42% of that for Tween-SLNs, respectively. Therefore, it can be concluded that both alkylated inulin-derived CAM-modified SLNs, especially the Inu18-SLNs had the improved gastrointestinal stability to resist the lipid degradation by lipase enzyme.

Pharmaceutical liposomal delivery-specific considerations of innovation and challenges.

Liposomal technology has been widely used in the pharmaceutical field for the preparation of nano-sized drug delivery systems based on natural or synthetic lipids. Liposomes possess many attractive properties, such as easy processing, high biocompatibility, adaptable drug loading, and improved PK profiles. In recent decades, great efforts have been made in this field, and dozens of liposomal medicines have been marketed worldwide and many more are under preclinical or clinical investigations. Liposomes can enhance the aqueous dissolution and stability of the encapsulated drugs and modulate the in vivo fate of the drugs (e.g., prolonged half-life and increased drug accumulation in the pathological sites). Therefore, liposomal technology can improve the druggability of the candidates, enhance treatment efficacy and reduce side effects. This review discusses the prospects of liposomal delivery, including the specific considerations of innovation and challenges.