title: Injectable and biodegradable poly(organophosphazene) hydrogel as a delivery system of docetaxel for cancer treatment.
abstract: Although docetaxel (DTX) is an advanced taxoid, further augmentation of its properties is still required, such as improvement in its low aqueous solubility. Herein, we report the development of biodegradable/injectable poly(organophosphazene) (PPZ) hydrogels for the delivery of DTX without the use of organic solvents. An aqueous solution of PPZ containing α-amino-ω-methoxy-poly(ethylene glycol) (AMPEG) 750 instead of AMPEG 550 was prepared, thereby increasing the erosion capacity of the hydrogel by judicious balance of the hydrophobic/hydrophilic moieties. The safety of the hydrogel was demonstrated using a biocompatibility test. The PPZ aqueous solution (8 wt%) containing DTX exhibited a thermosensitive sol-gel-sol transition that was independent of the concentration of DTX (1-3 mg/mL). The in vitro release study indicated that the dominant release mechanism was either erosion or diffusion/erosion-controlled release depending on the DTX content of the hydrogel. The in vivo anticancer effect of the intratumorally injected PPZ system in human gastric cancer cell-xenografted mice was evaluated, which demonstrated a significantly (p < 0.01) enhanced effect of the DTX-PPZ hydrogel system compared to the control (DTX solution, i.v.). In conclusion, the PPZ hydrogel may be a promising candidate for DTX delivery, affecting a decrease in the size of tumors with little toxicity prior to exeresis.
authors.affiliation: Center for Biomaterials, Korea Institute of Science and Technology, Seongbuk-gu, Seoul, Republic of Korea.
authors.forename: Jung-Kyo
authors.initials: JK
authors.lastname: Cho
authors.forename: Ji Min
authors.initials: JM
authors.lastname: Hong
authors.forename: Taesu
authors.initials: T
authors.lastname: Han
authors.forename: Han-Kwang
authors.initials: HK
authors.lastname: Yang
authors.forename: Soo-Chang
authors.initials: SC
authors.lastname: Song
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D000077143:Docetaxel; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage* / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D008422:Materials Testing / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009943:Organophosphorus Compounds / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry; D012995:Solubility; D013274:Stomach Neoplasms / Q000188:drug therapy; D043823:Taxoids / Q000008:administration & dosage* / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D009943:Organophosphorus Compounds; D011108:Polymers; D043823:Taxoids; C482466:alpha-Amino-omega-hydroxyl-poly(ethylene glycol); C515246:poly(organophosphazene); D000077143:Docetaxel; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols