In situ Hydrogels Prepared by Photo-initiated Crosslinking of Acrylated Polymers for Local Delivery of Antitumor Drugs

• Published in: Journal of pharmaceutical sciences 2023-07, Vol.112 (7), p.1863-1871
• Main Authors: Wang, Yuandou, Wang, Shuxin, Hu, Wenju, Kong, Shaowen, Su, Feng, Liu, Fusheng, Li, Suming
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - pharmacology; Biocompatibility; Cancer therapy; Chemical Sciences; Doxorubicin; Galenic pharmacology; Hydrogels - chemistry; Life Sciences; Local drug delivery; Mice; Pharmaceutical sciences; Photo-crosslinked hydrogel; Poly(ethylene glycol); Poly(ε-caporlactone); Polyesters - chemistry; Polyethylene Glycols - chemistry; Polymers; Polymers - chemistry; Spectroscopy, Fourier Transform Infrared
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1016/j.xphs.2023.02.004

A triblock copolymer was synthesized by ring opening polymerization of ε‐caprolactone in the presence of poly(ethylene glycol) (PEG). The resulted PCL-PEG-PCL triblock copolymer, PEG and monomethoxy (MPEG) were functionalized by end group acrylation. NMR and FT-IR analyses evidenced the successful synthesis and functionalization of polymers. A series of photo-crosslinked hydrogels composed of acrylated PEG-PCL-Acr and MPEG-Acr or PEG-Acr were prepared by exposure to visible light using lithium phenyl-2,4,6-trimethylbenzoylphosphinate as initiator. The hydrogels present a porous and interconnected structure as shown by SEM. The swelling performance of hydrogels is closely related to the crosslinking density and hydrophilic content. Addition of MPEG or PEG results in increase in water absorption capacity of hydrogels. In vitro degradation of hydrogels was realized in the presence of a lipase from porcine pancreas. Various degradation rates were obtained which mainly depend on the hydrogel composition. MTT assay confirmed the good biocompatibility of hydrogels. Importantly, in situ gelation was achieved by irradiation of a precursor solution injected in the abdomen of mice. Doxorubicin (DOX) was selected as a model antitumor drug to evaluate the potential of hydrogels in cancer therapy. Drug-loaded hydrogels were prepared by in situ encapsulation. In vitro drug release studies showed a sustained release during 28 days with small burst release. DOX-loaded hydrogels exhibit antitumor activity against A529 lung cancer cells comparable to free drug, suggesting that injectable in situ hydrogel with tunable properties could be most promising for local drug delivery in cancer therapy.