Double-Emulsion Copolyester Microcapsules for Sustained Intraperitoneal Release of Carboplatin
by
Aneta Cymbaluk-Płoska 1, Peter Sobolewski 2
, Anita Chudecka-Głaz 1, Ewa Wiśniewska 2, Joanna Łapczuk 3, Marcin Frankowski 4, Marek Droździk 3 and Miroslawa El Fray 2,*
Aneta Cymbaluk-Płoska 1, Peter Sobolewski 2, Anita Chudecka-Głaz 1, Ewa Wiśniewska 2, Joanna Łapczuk 3, Marcin Frankowski 4, Marek Droździk 3 and Miroslawa El Fray 2,*
1
Department and Clinic of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents, Pomeranian Medical University, ul. Powstanców Wlkp. 72, 70-111 Szczecin, Poland
2
Department of Polymer and Biomaterials Science, Faculty of Chemical Technology and Engineering, West Pomeranian University of Technology, Szczecin, Al. Piastów 45, 70-311 Szczecin, Poland
3
Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, ul. Powstanców Wlkp. 72, 70-111 Szczecin, Poland
4
Faculty of Chemistry, Adam Mickiewicz University in Poznań, ul. Uniwersytetu Poznańskiego 8, 61-614 Poznań, Poland
*
Author to whom correspondence should be addressed.
J. Funct. Biomater. 2019, 10(4), 55; https://doi.org/10.3390/jfb10040055
Received: 14 October 2019 / Revised: 2 December 2019 / Accepted: 4 December 2019 / Published: 6 December 2019
Despite on-going medical advances, ovarian cancer survival rates have stagnated. In order to improve IP delivery of platinum-based antineoplastics, we aimed to develop a sustained drug delivery system for carboplatin (CPt). Toward this aim, we pursued a double emulsion process for obtaining CPt-loaded microcapsules composed of poly(ethylene terephthalate-ethylene dilinoleate) (PET-DLA) copolymer. We were able to obtain PET-DLA microspheres in the targeted size range of 10–25 µm (median: 18.5 µm), to reduce intraperitoneal clearance by phagocytosis and lymphoid transit. Empty microspheres showed the lack of toxicity in vitro. The double emulsion process yielded 2.5% w/w CPt loading and obtained microcapsules exhibited sustained (>20 day) zero-order release. The encapsulated CPt was confirmed to be bioavailable, as the microcapsules demonstrated efficacy against human ovarian adenocarcinoma (SK-OV-3) cells in vitro. Following intraperitoneal injection in mice, we did not observe adhesions, only mild, clinically-insignificant, local inflammatory response. Tissue platinum levels, monitored over 14 days using atomic absorption spectroscopy, revealed low burst and reduced systemic uptake (plasma, kidney), as compared to neat carboplatin injection. Overall, the results demonstrate the potential of the developed microencapsulation system for long-term intraperitoneal sustained release of carboplatin for the treatment of ovarian cancer.
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Keywords:
controlled drug release; microencapsulation; carboplatin; ovarian cancer; intraperitoneal delivery
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MDPI and ACS Style
Cymbaluk-Płoska, A.; Sobolewski, P.; Chudecka-Głaz, A.; Wiśniewska, E.; Łapczuk, J.; Frankowski, M.; Droździk, M.; El Fray, M. Double-Emulsion Copolyester Microcapsules for Sustained Intraperitoneal Release of Carboplatin. J. Funct. Biomater. 2019, 10, 55.
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