Effects of cholesterol incorporation on the physicochemical, colloidal, and biological characteristics of pH-sensitive AB₂ miktoarm polymer-based polymersomes.
In our previous study, a histidine-based AB2 miktoarm polymer, methoxy poly(ethylene glycol)-b-poly(l-histidine)2 (mPEG-b-(PolyHis)2), was designed to construct pH-sensitive polymersomes that transform in acidic pH; the polymer self-assembles into a structure that mimics phospholipids. In this study, the polymersomes further imitated liposomes due to the incorporation of cholesterol (CL). The hydrodynamic radii of the polymersomes increased with increasing CLwt% (e.g., 70 nm for 0 wt% vs. 91 nm for 1 wt%), resulting in an increased capacity for encapsulating hydrophilic drugs (e.g., 0.92 μL/mg for 0 wt% vs. 1.42 μL/mg for 1 wt%). The CL incorporation enhanced the colloidal stability of the polymersomes in the presence of serum protein and retarded their payload release. However, CL-incorporating polymersomes still demonstrated accelerated release of a hydrophilic dye (e.g., 5(6)-carboxyfluorescein (CF)) below pH 6.8 without losing their desirable pH sensitivity. CF-loaded CL-incorporating polymersomes showed better cellular internalization than the hydrophilic CF, whereas doxorubicin (DOX)-loaded CL-incorporating polymersomes presented similar or somewhat lower anti-tumor effects than free hydrophobic DOX. The findings suggest that CL-incorporating mPEG-b-(PolyHis)2-based polymersomes may have potential for intracellular drug delivery of chemical drugs due to their improved colloidal stability, lower drug loss during circulation, acidic pH-induced drug release, and endosomal disruption.
Department of Pharmaceutics and Pharmaceutical Chemistry, The University of Utah, 30 S 2000 E, Room 2972, Salt Lake City, UT 84112, USA.
Haiqing
H
Yin
Department of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, College of Pharmacy, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-743, Republic of Korea.
Han Chang
HC
Kang
Department of Polymer Science and Engineering, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejeon 305-764, Republic of Korea.
Kang Moo
KM
Huh
Department of Pharmaceutics and Pharmaceutical Chemistry, The University of Utah, 30 S 2000 E, Room 2972, Salt Lake City, UT 84112, USA; Utah-Inha Drug Delivery Systems (DDS) and Advanced Therapeutics Research Center, 7-50 Songdo-dong, Yeonsu-gu, Incheon 406-840, Republic of Korea. Electronic address: you.bae@utah.edu.
You Han
YH
Bae
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002627:Chemistry, Physical; D002784:Cholesterol / Q000737:chemistry*; D003102:Colloids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006863:Hydrogen-Ion Concentration; D061986:MCF-7 Cells; D015394:Molecular Structure; D010316:Particle Size; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013499:Surface Properties
D000970:Antineoplastic Agents; D003102:Colloids; D011108:Polymers; D004317:Doxorubicin; D002784:Cholesterol
Cholesterol; Colloidal stability; Miktoarm polymer; Poly(histidine); Polymersome; pH-sensitive