Irinotecan-encapsulated double-reverse thermosensitive nanocarrier system for rectal administration.
Intravenously administered for the treatment of rectum cancer, irinotecan produces severe side effects due to very high plasma concentrations. A novel irinotecan-encapsulated double reverse thermosensitive nanocarrier system (DRTN) for rectal administration was developed as an alternative. The DRTN was fabricated by dispersing the thermosensitive irinotecan-encapsulated solid lipid nanoparticles (SLN) in the thermosensitive poloxamer solution. Its gel properties, pharmacokinetics, morphology, anticancer activity and immunohistopathology were assessed after its rectal administration to rats and tumor-bearing mice. In the DRTN, the solid form of the SLN and the liquid form of the poloxamer solution persisted at 25 °C; the former melted to liquid, and the latter altered to gel at 36.5 °C. The DRTN was easily administered to the anus, gelling rapidly and strongly after rectal administration. Compared to the conventional hydrogel and intravenously administered solution, it retarded dissolution and initial plasma concentration. The DRTN gave sustained release and nearly constant plasma concentrations of irinotecan at 1-3 h in rats, resulting in improved anticancer activity. It induced no damage to the rat rectum and no body weight loss in tumor-bearing mice. Thus, this irinotecan-encapsulated DRTN associated with a reduced burst effect, lack of toxicity and excellent antitumor efficacy would be strongly recommended as a rectal pharmaceutical product alternative to commercial intravenous injection in the treatment of rectum and colon cancer.
a College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University , Ansan , South Korea.|b Department of Pharmacy, Quaid-I-Azam University , Islamabad , Pakistan.
Fakhar Ud
FU
Din
c College of Pharmacy, Yeungnam University , Gyongsan , South Korea.
Ju Yeon
JY
Choi
a College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University , Ansan , South Korea.
Dong Wuk
DW
Kim
a College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University , Ansan , South Korea.|d International Center of Chemical and Biological Sciences, University of Karachi , Karachi , Pakistan.
Omer
O
Mustapha
a College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University , Ansan , South Korea.
Dong Shik
DS
Kim
c College of Pharmacy, Yeungnam University , Gyongsan , South Korea.
Raj Kumar
RK
Thapa
e College of Oriental Medicine, Daegu Haany University , Gyongsan , South Korea.
Sae Kwang
SK
Ku
f School of Pharmacy, Sungkyunkwan University , Suwon , South Korea , and.
Yu Seok
YS
Youn
g College of Pharmacy, Chung-Ang University , Seoul , Republic of Korea.
Kyung Taek
KT
Oh
c College of Pharmacy, Yeungnam University , Gyongsan , South Korea.
Chul Soon
CS
Yong
c College of Pharmacy, Yeungnam University , Gyongsan , South Korea.
Jong Oh
JO
Kim
a College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University , Ansan , South Korea.
Han-Gon
HG
Choi
D061605:Administration, Intravenous; D000285:Administration, Rectal; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004339:Drug Compounding; D005260:Female; D006801:Humans; D020100:Hydrogels; D000077146:Irinotecan; D008055:Lipids / Q000737:chemistry*; D008297:Male; D008819:Mice, Nude; D050997:Nanomedicine; D053758:Nanoparticles; D044367:Phase Transition; D020442:Poloxamer / Q000737:chemistry*; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D044366:Transition Temperature; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D008055:Lipids; D020442:Poloxamer; D000077146:Irinotecan; D002166:Camptothecin
Irinotecan; anti-tumor efficacy; burst effect; double reverse thermosensitive nanocarrier; rectal administration; toxicity