PEGylated polypeptide lipid nanocapsules to enhance the anticancer efficacy of erlotinib in non-small cell lung cancer.
In this study, a core-shell type polypeptide-based lipid nanocapsule was developed to enhance anticancer efficacy of erlotinib in non-small cell lung cancers. Mean particle size of PEGylated polypeptide-lipid nanocapsules (PLN) for erlotinib (ERL) delivery was ∼200nm with an effective surface charge of -20mV. Protective PEGylated polypeptide layer acted as a molecular fence and effectively controlled the diffusion of erlotinib from the lipid nanocapsule core, whereas pH-responsiveness of poly(L-aspartic acid) accelerated the release of erlotinib in acidic conditions. Blank lipid nanocapsules showed excellent biocompatibility. ERL-loaded PLN (ERL-PLN) showed dose-dependent cytotoxicity in NCI-H358 and HCC-827 lung cancer cells. ERL-PLN treatment resulted in a superior tumor regression profile in a xenograft tumor model, compared to free ERL and control, suggesting high therapeutic efficacy. ERL-PLN-treated mice showed 5- and 2-fold smaller tumor volume compared to control and free ERL groups, respectively. Based on these results, PLN provide a promising drug delivery approach for lung cancer therapy.
College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan 712-749, South Korea.
Jeonghwan
J
Kim
College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan 712-749, South Korea.
Thiruganesh
T
Ramasamy
College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan 712-749, South Korea.
Ju Yeon
JY
Choi
College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan 712-749, South Korea.
Ssang Tae
ST
Kim
School of Pharmacy, SungKyunKwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon 440-746, South Korea.
Yu Seok
YS
Youn
College of Pharmacy, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan 426-791, South Korea.
Han-Gon
HG
Choi
College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan 712-749, South Korea. Electronic address: csyong@yu.ac.kr.
Chul Soon
CS
Yong
College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan 712-749, South Korea. Electronic address: jongohkim@yu.ac.kr.
Jong Oh
JO
Kim
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival; D004058:Diffusion; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D057446:Hydrodynamics; D006863:Hydrogen-Ion Concentration; D008055:Lipids / Q000737:chemistry*; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053769:Nanocapsules / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry; D009368:Neoplasm Transplantation; D010316:Particle Size; D010455:Peptides / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D013499:Surface Properties
D000970:Antineoplastic Agents; D004337:Drug Carriers; D008055:Lipids; D053769:Nanocapsules; D010455:Peptides; C017645:polyaspartate; D011092:Polyethylene Glycols; D000069347:Erlotinib Hydrochloride
Antitumor efficacy; Erlotinib; Lung cancer; Nanocapsules; Polypeptide