Intratumoral Injection Administration of Irinotecan-Loaded Microspheres: In Vitro and In Vivo Evaluation
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To reduce the toxic and side effects of intravenous chemotherapeutic drugs on the tumor-patients, the aims of this study were to design and study intratumor-administrated irinotecan-loaded PLGA microspheres (CPT-11-PLGA-MS) in vitro and in vivo according to the structure characteristics of CPT-11. PLGA microspheres containing irinotecan were prepared by emulsion solvent evaporation method and evaluated in terms of their morphology, particle size analysis, in vitro drug release, drug retention and leakage studies in vivo, and pharmacodynamics studies. The CPT-11-PLGA-MS were spherical with mean size of 9.29 ± 0.02 μm, and average encapsulation efficiency were measured of 77.97 ± 1.26% along with the average drug loading of 7.08 ± 0.11%. DSC results indicated that the drug existed in the phase of uncrystallization in the microspheres. The formulation of CPT-11-PLGA-MS could prolong the in vitro drug release to 16 days following Weibull equation. In CPT-11-PLGA-MS after intratumor injection administration was significantly improved. The results demonstrated that the slow-sustained release of CPT-11-PLGA-MS in tumor tissue after intratumor injection of microspheres can reduce the drug leakage to the circulation system, maintain the drug retention, and improve the therapeutic effect, which could become a promising drug delivery system for CPT-11 and could maintain the most effective concentration at the target site to maximum limit.
KEY WORDSirinotecan intratumor-administration microspheres 7-ethyl-10-hydroxycamptothecin lactone ring structure
The authors would like to express thanks to the School of Pharmaceutical Science, Shandong University for providing the required infrastructure to carry out the study.
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Conflict of Interest
The work described has not been submitted elsewhere for publication in whole or in part, and all the authors listed have approved the manuscript that is enclosed. The authors declare that they have no conflict of interest. The authors alone are responsible for the content and writing of this article.
- 6.Yang X, Hu Z, Sui YC, et al. Simultaneous determination of the lactone and carboxylate forms of irinotecan (CPT-11) and its active metabolite SN-38 by high-performance liquid chromatography: application to plasma pharmacokinetic studies in the rat. J Chromatogr B Analyt Technol Biomed Life Sci. 2005;821(2):221–8.CrossRefPubMedGoogle Scholar
- 9.Jmm L, Lee M H, Garon E, et al. Phase I trial of intratumoral injection of CCL21 gene modified dendritic cells in lung cancer elicits tumor-specific immune responses and CD8+ T cell infiltration Clinical Cancer Research An Official Journal of the American Association for Cancer Research, 2017.Google Scholar
- 10.Mehta HJ, Begnaud A, Penley AM, Wynne J, Malhotra P, Fernandez-Bussy S, et al. Treatment of isolated mediastinal and hilar recurrence of lung cancer with bronchoscopic endobronchial ultrasound guided intratumoral injection of chemotherapy with cisplatin. Lung Cancer. 2015;90(3):542–7.CrossRefPubMedGoogle Scholar
- 11.Liu Q S, Zhang S Y, Mei Q L, et al. Percutaneous intratumoral injection of lipiodol emulsion of vinorelbine for rabbits with VX2 tumor:an experimental study Journal of Interventional Radiology, 2016.Google Scholar
- 13.Kwon GS, You HB, Cremers H, et al. Release of macromolecules from albumin-heparin microspheres. Int J Pharm. 2017;79(2–3):191–8.Google Scholar
- 15.Nishino S, Yoshizawa H, Kitamura Y. Preparation of polylactide microspheres with surface morphology control. J Chem Ind Eng. 2002;53:202–3.Google Scholar
- 17.Machida Y, Onishi H, Morikawa A. Antitumour characteristics of irinotecan-containing microspheres of poly-d,l-lactic acid or poly(d,l-lactic acid-co-glycolic acid) copolymers. S.t.p.pharma Pratiques. 1998;8(3):175–81.Google Scholar
- 20.Tian L, Gao J, Yang Z, et al. Tamibarotene-Loaded PLGA Microspheres for Intratumoral Injection Administration: Preparation and Evaluation. AAPS PharmSciTech, 2017:1–9.Google Scholar