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Fabrication of TPGS-Stabilized Liposome-PLGA Hybrid Nanoparticle Via a New Modified Nanoprecipitation Approach: In Vitro and In Vivo Evaluation.
Pharmaceutical Research 2018 August 31
PURPOSE: In this study, a new modified nanoprecipitation approach that more efficient and simpler than conventional approach was developed to synthesize D-alpha-Tocopheryl polyethylene glycol 1000 succinate stabilized liposome-PLGA hybrid nanoparticle, loaded with simvastatin (ST-TLPN).
METHODS: The optimum formulation was screened via investigation of the impact of TPGS mass within polymeric core and lipid shell on the physicochemical properties of nanoparticles respectively. FTIR, and drug release of ST-TLPN were also systematically determined. Finally, the cellular internalization was evaluated using the murine macrophage cell line, in vivo pharmacokinetic behavior and antiatherogenic efficacies were elaborately examined in atherosclerotic rabbit models.
RESULTS: With the weight ratio of TPGS-to-PLGA in organic phase of 30% and TPGS-to-lipid in aqueous phase of 35%, ST-TLPN exhibited core-shell structure, sub-100 nm size, EE% of over 90% and a slow release profile. The excellent cellular uptake was displayed in RAW264.7 cell line. Improved pharmacokinetic behavior, and enhanced antiatherogenic efficacy of ST-TLPN in the model animals were also revealed compared with ST-loaded PLGA nanoparticles.
CONCLUSION: These findings suggest the modified nanoprecipitation method holds great potential for fabricating LPN, aided by the multiple functions of TPGS. And the prepared TLPN is a promising delivery system for use in the pharmaceutical field.
METHODS: The optimum formulation was screened via investigation of the impact of TPGS mass within polymeric core and lipid shell on the physicochemical properties of nanoparticles respectively. FTIR, and drug release of ST-TLPN were also systematically determined. Finally, the cellular internalization was evaluated using the murine macrophage cell line, in vivo pharmacokinetic behavior and antiatherogenic efficacies were elaborately examined in atherosclerotic rabbit models.
RESULTS: With the weight ratio of TPGS-to-PLGA in organic phase of 30% and TPGS-to-lipid in aqueous phase of 35%, ST-TLPN exhibited core-shell structure, sub-100 nm size, EE% of over 90% and a slow release profile. The excellent cellular uptake was displayed in RAW264.7 cell line. Improved pharmacokinetic behavior, and enhanced antiatherogenic efficacy of ST-TLPN in the model animals were also revealed compared with ST-loaded PLGA nanoparticles.
CONCLUSION: These findings suggest the modified nanoprecipitation method holds great potential for fabricating LPN, aided by the multiple functions of TPGS. And the prepared TLPN is a promising delivery system for use in the pharmaceutical field.
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