Radio-frequency plasma polymerized biodegradable carrier for in vivo release of cis-platinum

// Sudhir Bhatt 1, 3 , Fatemeh Valamanesh 2 , Jerome Pulpytel 1 , Rea Lo Dico 2 , Aliby Baiyukha 1 , Iman Al-dybiat 2 , Marc Pocard 2 , Farzaneh Arefi-Khonsari 1 , Massoud Mirshahi 2 1 Sorbonne Universites, UPMC Univ. Paris 6, CNRS, Laboratoire Interfaces et Systemes Electrochimiques, 75005, Paris, France 2 Sorbonne Paris Cite Universites, UMR Univ. Paris 7, INSERM U965 Carcinose, Angiogenese et Recherche Translationnelle, L’Hopital Lariboisiere, 75010, Paris, France 3 Current address: Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, 23508, VA, USA Correspondence to: Massoud Mirshahi, email: massoud.mirshahi@inserm.fr Keywords: plasma polymers, biodegradable coatings, in vivo drug delivery system, anti-cancer drug, targeted therapy Received: May 11, 2016 Accepted: July 19, 2016 Published: July 29, 2016 ABSTRACT A low pressure plasma process based on plasma deposition has been used to develop a drug delivery strategy. In this study, a drug delivery system based on different layers of plasma co-polymerized Poly e-caprolactone-Polyethylene glycol (PCL-PEG) co-polymers was deposited on biocompatible substrates. Cis-platinum (118 μgm/cm 2 ) was used as an anti-cancer drug and incorporated for local delivery of the chemotherapeutic agent. The co-polymer layers and their interaction with cancer cells were analyzed by scanning electron microscopy. Our study showed that the plasma-PCL-PEG coated cellophane membranes, in which the drug, was included did not modify the flexibility and appearance of the membranes. This system was actively investigated as an alternative method of controlling localized delivery of drug in vivo . The loading of the anti-cancer drug was investigated by UV-VIS spectroscopy and its release from plasma deposited implants against BALB/c mice liver tissues were analyzed through histological examination and apoptosis by TUNEL assay. The histological examination of liver tissues revealed that when the plasma-modified membranes encapsulated the cis-platinum, the Glisson’s capsule and liver parenchyma were damaged. In all cases, inflammatory tissues and fibrosis cells were observed in contact zones between the implant and the liver parenchyma. In conclusion, low pressure plasma deposited uniform nano-layers of the co-polymers can be used for controlled release of the drug in vivo.