Modification of paclitaxel-loaded solid lipid nanoparticles with 2-hydroxypropyl-β-cyclodextrin enhances absorption and reduces nephrotoxicity associated with intravenous injection.
BACKGROUND
Paclitaxel (PTX) solid lipid nanoparticles (SLNs) modified with 2-hydroxypropyl-β-cyclodextrin (HPCD) were evaluated for their ability to enhance PTX absorption and reduce the nephrotoxicity accompanying intravenous administration.


METHODS
PTX-loaded SLNs (PS) and PTX-loaded SLNs modified using HPCD (PSC) were prepared by hot-melted sonication. The anticancer activity of PSC was evaluated in MCF-7 cells, and confocal microscopy was used to quantify the cellular uptake. The pharmacokinetic profiles of PTX released from PSC after intravenous administration were studied in rats. Furthermore, kidney toxicity was determined by measuring the kidney size and plasma creatinine level.


RESULTS
PSC were successfully prepared by hot-melted sonication and had smaller diameters than PS. PSC exhibited improved anticancer activity and cellular uptake in MCF-7 cells. Furthermore, PSC showed higher bioavailability in rats after intravenous administration than PTX solution; however, no significant differences in kidney toxicity were observed.


CONCLUSIONS
Based on these results, PSC could be considered as a potential therapeutic PTX delivery system for breast cancer with low renal toxicity.
College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon, South Korea.
Jong-Suep
JS
Baek
College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon, South Korea.
Ju-Heon
JH
Kim
College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon, South Korea.
Jeong-Sook
JS
Park
College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon, South Korea.
Cheong-Weon
CW
Cho
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000418:Albumins / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics; D017209:Apoptosis; D019540:Area Under Curve; D001943:Breast Neoplasms; D049109:Cell Proliferation; D002470:Cell Survival; D003404:Creatinine / Q000097:blood; D004337:Drug Carriers / Q000493:pharmacokinetics*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects; D008055:Lipids / Q000737:chemistry*; D061986:MCF-7 Cells; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry*; D009368:Neoplasm Transplantation; D017239:Paclitaxel / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D047392:beta-Cyclodextrins / Q000737:chemistry*
C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D000970:Antineoplastic Agents; D004337:Drug Carriers; D008055:Lipids; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D003404:Creatinine; D017239:Paclitaxel
2-hydroxypropyl-β-cyclodextrin; bioavailability; nephrotoxicity; paclitaxel; solid lipid nanoparticles