Tumor targeting effects of a novel modified paclitaxel-loaded discoidal mimic high density lipoproteins.
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.


CONCLUSIONS
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.
Department of Pharmaceutics, China Pharmaceutical University , Nanjing , PR China .
Ji
J
Wang
Junting
J
Jia
Jianping
J
Liu
Hongliang
H
He
Wenli
W
Zhang
Zhenghua
Z
Li
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D040761:Biomimetic Materials / Q000008:administration & dosage / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D002788:Cholesterol Esters / Q000737:chemistry; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D008075:Lipoproteins, HDL / Q000737:chemistry*; D061986:MCF-7 Cells; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D010316:Particle Size; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism; D014018:Tissue Distribution
D000972:Antineoplastic Agents, Phytogenic; D002788:Cholesterol Esters; D004337:Drug Carriers; D008075:Lipoproteins, HDL; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D017239:Paclitaxel; C013440:cholesteryl succinate