Papain has been known by many decades for wounded tissues repair. However, papain stability is not high enough to be commercialized in a stable pharmaceutical form; therefore its use is limited. The strategy to entrap papain into a polymeric matrix to provide an adequate drug delivery system consists of an alternative to this problem. The purpose of this study was to assess in vitro and in vivo four polymers cytotoxicity and ability to cause cutaneous irritation to be applied as a suitable papain delivery system. A Monocomponent (MSD) and Bicomponent Silicone Dispersions (BSD) and, Natural Rubber Bicentrifuged Latex (NRBL) and an Acrylic Adhesive (AA) were selected. The cytotoxicity was firstly assessed by the Neutral Red Uptake Method. Non-cytotoxic polymers were then submitted to in vivo Cutaneous Irritation Test. Both silicone dispersions were found non-cytotoxic, and NRBL and AA polymers showed cytotoxicity. MSD and BSD polymers did not cause any cutaneous reactions.Colegio de Farmacéuticos de la Provincia de Buenos Aire