OBJECTIVE: Monocholesterylsuccinate (CHS)-modified paclitaxel-loaded discoidal reconstituted high density lipoproteins (cP-d-rHDL) as novel biomimetic nanocarriers that were developed for tumor targeting delivery to avoid unexpected drug leakage from discoidal reconstituted high density lipoproteins (d-rHDL) during remodeling process associated with lecithin-cholesterol acyltransferase (LCAT). METHODS: Their in vitro characterizations and biomimetic properties, simultaneously tumor distribution and pharmacodynamics in tumor bearing mice were elaborately investigated. RESULTS: In vitro characterization results showed that cP-d-rHDL had nano-size diameter, high negative zeta potential and high entrapment efficiency (EE). Furthermore, morphology study indicated that cP-d-rHDL did not remodel in the presence of LCAT, compared with that of paclitaxel-loaded d-rHDL (P-d-rHDL, not modified). And cellular uptake, together with cytotoxicity toward tumor cells of cP-d-rHDL was not affected after interaction with LCAT. Tumor distribution and pharmacodynamics tests revealed that cP-d-rHDL possessed specific targeting property and anti-tumor efficacy. CONCLUSION: cP-d-rHDL served to restrain remodeling process and drug leakage, at the same time reinforce the targeting effect, and could act as a potential drug delivery system for cancer therapy.
OBJECTIVE:Monocholesterylsuccinate (CHS)-modified paclitaxel-loaded discoidal reconstituted high density lipoproteins (cP-d-rHDL) as novel biomimetic nanocarriers that were developed for tumor targeting delivery to avoid unexpected drug leakage from discoidal reconstituted high density lipoproteins (d-rHDL) during remodeling process associated with lecithin-cholesterol acyltransferase (LCAT). METHODS: Their in vitro characterizations and biomimetic properties, simultaneously tumor distribution and pharmacodynamics in tumor bearing mice were elaborately investigated. RESULTS: In vitro characterization results showed that cP-d-rHDL had nano-size diameter, high negative zeta potential and high entrapment efficiency (EE). Furthermore, morphology study indicated that cP-d-rHDL did not remodel in the presence of LCAT, compared with that of paclitaxel-loaded d-rHDL (P-d-rHDL, not modified). And cellular uptake, together with cytotoxicity toward tumor cells of cP-d-rHDL was not affected after interaction with LCAT. Tumor distribution and pharmacodynamics tests revealed that cP-d-rHDL possessed specific targeting property and anti-tumor efficacy. CONCLUSION:cP-d-rHDL served to restrain remodeling process and drug leakage, at the same time reinforce the targeting effect, and could act as a potential drug delivery system for cancer therapy.
Authors: Ton Wang; Chitra Subramanian; Minzhi Yu; Peter T White; Rui Kuai; Jaquelyn Sanchez; James J Moon; Barbara N Timmermann; Anna Schwendeman; Mark S Cohen Journal: Surgery Date: 2019-07-29 Impact factor: 3.982