title: Convergent in situ assembly of injectable lipogel for enzymatically controlled and targeted delivery of hydrophilic molecules.
abstract: Applications of liposomes are limited due to their rapid blood clearance and non-specific biodistribution. Surface modification of liposomes could overcome these disadvantages. However, direct coating of liposome surface may cause disruption of liposomes. Herein we present a "top-down" method to coat liposomes in situ with tumor (CD44 receptor) targeting polymer, hyaluronan (HA), by taking advantages of "click" type chemistries and enzymatic degradation. Liposomes entrapped within HA gel were stable without leaking of small cargo molecules from the interior of the liposomes. This injectable liposome-in-hydrogel (lipogel) drug delivery system can achieve sequential two-step release: (1) liposomes release from lipogel after HA degradation; (2) small molecules release from liposomes after the liposomes disruption (either before or after cellular uptake). Similarly to HA coating, this strategy could be used for in situ "top-down" modification of liposomes with other targeting biopolymers. Additionally, it provides the possibility to deliver different types of molecules from two compartments of the lipogel, i.e. large biomacromolecules from the exterior of liposomes and small hydrophilic molecules from the interior of liposomes, locally and systemically.
authors: Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, No. 64 Mianshan Road, Mianyang, 621900, Sichuan Province, China. Electronic address: yangxia.youka@caep.cn.
authors: Xia
authors: X
authors: Yang
authors: Department of Chemistry-Angstrom, Uppsala University, Uppsala, SE 751 21, Sweden.
authors: Liyang
authors: L
authors: Shi
authors: Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, No. 64 Mianshan Road, Mianyang, 621900, Sichuan Province, China.
authors: Xin
authors: X
authors: Guo
authors: Department of Chemistry-Angstrom, Uppsala University, Uppsala, SE 751 21, Sweden.
authors: Jinxu
authors: J
authors: Gao
authors: Department of Chemistry-Angstrom, Uppsala University, Uppsala, SE 751 21, Sweden. Electronic address: dmitri.ossipov@kemi.uu.se.
authors: Dmitri
authors: D
authors: Ossipov
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D005452:Fluoresceins / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000737:chemistry / Q000378:metabolism; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity; D051379:Mice; D008856:Microscopy, Fluorescence; D041681:NIH 3T3 Cells; D012212:Rheology
chemical_list: C497483:CD44 protein, human; D005452:Fluoresceins; D005456:Fluorescent Dyes; D018960:Hyaluronan Receptors; D008081:Liposomes; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D006820:Hyaluronic Acid; C007740:fluorexon
keywords: Delivery system; Enzymatic degradation; Hyaluronan; In situ coating; Injectable lipogel