Development, safety and efficacy evaluation of actinic damage retarding nano-pharmaceutical treatments in oculocutaneous albinism

Abstract

Introduction: There are at least 17 000 Persons living with albinism (PLWA) in Zimbabwe. Oculocutaneous albinism (OCA) is a congenital amelanistic pigmentation disorder that affects all known vertebrates and has no known cure. Melanogenesis is the body’s primary protection from actinic damage, which summarizes all the acute and chronic solar induced adverse dermatological conditions. This impairment therefore makes PLWA highly susceptible to all forms of this damage. Problem statement: Commercial products for actinic damage in PLWA are not readily available. Chemical sunscreens used by PLWA are ineffective and do not treat symptoms of actinic damage. The possible use of promising broad spectrum physical sunscreens in albinistic treatments is hindered by their opaque and un-aesthetic nature. Research hypothesis: A treatment based on nanometric TiO2 and ZnO incorporating the active extracts of A. excelsa, T. emetica and M. flabellifolia will be aesthetic, efficacious and safe in retarding and alleviating all forms of actinic damage in PLWA. Research aims: To develop albinistic actinic damage treatments, using nano TiO2 and ZnO as sun-blocks and incorporating selected herbs. The dermato-pharmacokinetics, stability, efficacy, toxicity and aesthetics of the resultant formulation on albinistic skin types were also investigated in this study. Materials and methods: Emulsion formulation was done according to FDA-CFSAN, COLIPA, and OECD mandated technical guidelines and testing methods. Formulation skin sensitivity were evaluated through Draize ocular and skin sensitivity tests as well as in-vivo patch tests guided by OECD 428/404 technical guidelines and opinion SCCNFP 0750/03. Percutaneous absorption and albinistic skin dermato-pharmacokinetics were evaluated ex-vivo using Franz diffusion tests and sequential adhesive tape stripping respectively according to OECD guidelines 428 and SCCNFP opinions as well as related work done by A O Gamer and Diembeck et al as guides. Analysis for Ti and Zn were done by ICP-AES and Flame AAS respectively. Efficacy and SPF testing was done as per FDA–CFSAN, Colipa and OECD M389/EN mandated test methods. Principal Results: SPF 16, aesthetic and stable emulsions were formulated. Negligible irritation indices for the treatment were recorded for Draize and human patch testing. No percutaneous absorption was observed for ex-vivo diffusion tests and sequential tape stripping tests. Different skin reservoir properties were observed at different skin sites Conclusions: The studies demonstrate, direct evidence that neither Zn nor Ti can penetrate actinic damaged skin regardless of anatomical site and that albinistic dermato-pharmacokinetics are depended on anatomical region and extent of UVR exposure. The high extraction yields and the phyto-constituents of the selected herbs show a correlation with the traditional uses of the plants in traditional medicine. All sensitivity tests showed negligible irritation potential. Based on the foregoing, it is concluded that, incorporation of nanometric TiO2, ZnO and herbs in treatments to retard actinic damage in PLWA is feasible, aesthetic, efficacious, and commercializable and does not pose any health risk.