title: Development of paclitaxel-loaded liposomal nanocarrier stabilized by triglyceride incorporation.
abstract: Studies have highlighted the challenge of developing injectable liposomes as a paclitaxel (PTX) carrier, a challenge attributable to the limitations in liposomal stability caused by PTX loading. Poor stability of PTX-loaded liposomes is caused by PTX-triggered aggregation or fusion of liposomal membranes and is exacerbated in the presence of PEGylated lipid. In the present study, the effect of triglyceride incorporation on the stability of PTX-loaded/PEGylated liposomes was explored. Incorporation of a medium chain triglyceride Captex 300 into saturated phosphatidylcholine (PC)-based liposomes (1,2-dimyristoyl-sn-glycero-3-phosphocholine [DMPC]:cholesterol [CHOL]:N-(Carbonyl-methoxypolyethyleneglycol 2000)-1, 2-distearoyl-sn-glycero-3-phospho-ethanolamine [PE-PEG]), produced a fine, homogeneous, and membrane-filterable PTX-loaded liposomes fulfilling the requirement of an injectable lipid formulation. Triglyceride incorporation also greatly inhibited the time-dependent leakage of PTX from saturated PC-based liposomes, which appears to be mediated by the inhibition of liposome fusion. In contrast, triglyceride incorporation induced the destabilization and PTX leakage of unsaturated PC-based liposomes, indicating the opposite effect of triglyceride depending on the fluidity status of PC constituting the liposomal membrane. PTX release profile and the in vitro and in vivo anticancer efficacy of triglyceride-incorporated DMPC:CHOL:PE-PEG liposomes were similar to Taxol®while the toxicity of liposomal PTX was significantly lower than that of Taxol. Taken together, triglyceride incorporation provided an injectable PTX formulation by functioning as a formulation stabilizer of PEGylated/saturated PC-based liposomes.
authors.affiliation: Department of Bioscience and Bioengineering, Sejong University, Seoul.
authors.forename: Soon-Seok
authors.initials: SS
authors.lastname: Hong
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan.
authors.forename: Ju Yeon
authors.initials: JY
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan.
authors.forename: Jong Oh
authors.initials: JO
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Woosuk University, Wanju-gun, Jeollabuk-do.
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Lee
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Science and Technology, Ajou University, Suwon, Republic of Korea.
authors.forename: So Hee
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Bioscience and Bioengineering, Sejong University, Seoul.
authors.forename: Soo-Jeong
authors.initials: SJ
authors.lastname: Lim
keywords: PEGylation; formulation; liposome; paclitaxel; stability; triglyceride