A thermoresponsive chitosan-based in situ gel formulation incorporated with 5-FU loaded nanoerythrosomes for fibrosarcoma local chemotherapy

被引:6
作者
Javadi, Parisa [1 ]
Derakhshan, Mohammad Ali [1 ]
Heidari, Reza [2 ]
Ashrafi, Hajar [3 ]
Azarpira, Negar [4 ]
Shahbazi, Mohammad Ali [5 ,6 ]
Azadi, Amir [1 ,2 ,3 ]
机构
[1] Shiraz Univ Med Sci, Sch Adv Med Sci & Technol, Dept Med Nanotechnol, Shiraz, Iran
[2] Shiraz Univ Med Sci, Pharmaceut Sci Res Ctr, Shiraz, Iran
[3] Shiraz Univ Med Sci, Sch Pharm, Dept Pharmaceut, Shiraz, Iran
[4] Shiraz Univ Med Sci, Transplant Res Ctr, Shiraz, Iran
[5] Univ Groningen, Univ Med Ctr Groningen, Dept Biomed Engn, Antonius Deusinglaan 1, NL-9713 AV Groningen, Netherlands
[6] Zanjan Univ Med Sci, Zanjan Pharmaceut Nanotechnol Res Ctr ZPNRC, Zanjan, Iran
关键词
In situ gel; Nanoerythrosome; Local cancer chemotherapy; Fibrosarcoma; Solid tumor; 5-FU; DRUG-DELIVERY; ERYTHROCYTE-MEMBRANE; BIODEGRADABLE MICROSPHERES; SUSTAINED DELIVERY; MALIGNANT GLIOMA; 5-FLUOROURACIL; NANOPARTICLES; HYDROGEL; RADIOSENSITIZATION; CONVERSION;
D O I
10.1016/j.ijbiomac.2024.134781
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Local administration of drugs at tumor sites over an extended period of time shows potential as a promising approach for cancer treatment. In the present study, the temperature-induced phase transition of chitosan and poloxamer 407 is used to construct an injectable hydrogel encapsulating 5-FU- loaded nanoerythrosome (5-FUNER-gel). The 5-FU-NERs were found to be spherical, measuring approximately 115 f 20 nm in diameter and having a surface potential of-7.06 f 0.4. The drug loading efficiency was approximately 40 %. In situ gel formation took place within 15 s when the gel was exposed to body temperature or subcutaneous injection. A sustained release profile was observed at pH 7.4 and 6.8, with a total 5-FU release of 76.57 f 4.4 and 98.07 f 6.31 in 24 h, respectively. MTT, Live/dead, and migration assays confirmed the cytocompatibility of the drug carrier and its effectiveness as a chemotherapeutic formulation. After in vivo antitumor assessment in a subcutaneous autograft model, it was demonstrated that tumor growth inhibition in 14 days was 90 %. Therefore, the obtained injectable chitosan-based hydrogel containing 5-FU-loaded nanoerythrosomes illustrated promising potential as a candidate for local and enhanced delivery of chemotherapeutics at the tumor site.
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页数:16
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