Development of formulation with wound healing property and tissue remodeling

Abstract

Secondary metabolites produced by microorganisms are known due to their several biotechnological applications, and are also good lead compounds suitable for further modification during drug development. Annularins is a class of molecules commonly found in fungi, and annularin I have moderate antimicrobial action in pathogens commonly present in infections. In previous in vitro studies on human umbilical vein endothelial cells (HUVECs) and normal human fibroblasts FN1 (FN1), annularin I promoted cell proliferation. Analyzes of the expression of proteins involved in proliferation, senescence, and cell cycle phases indicated the perspective of therapeutic application of this compound in the process of regeneration, remodeling and tissue repair in wound healing. In the in vivo study, in a murine model of wounds, cream formulations carrying annularin I at 0.0005, 0.003 and 0.03% were effective in wound healing with action in regeneration and remodeling. Significant collagen production and absence of keloids were observed. The safety analysis by hematological and biochemical measurement of hepatic and renal parameters indicated absence of toxicity in animals treated with the cream formulation until 14 days. The formulation used in the study was a non-ionic base cream prepared according to the 6th edition of the Brazilian Pharmacopoeia, and the concentrations used in the formulation were based on previous in vitro results. In this context, this proposal aims to advance the development of a formulation with annularin I at 0.003%, following the protocols defined by the Organization for Economic Co-operation and Development (OECD), and the rules of The Brazilian Health Regulatory Agency (ANVISA) for the registration of a dermatological grade 2 product for topical use. Initially for cosmetic use and later for the wound healing in tissue repair and remodeling. The proposed tests refer to the analysis of dermal toxicity and sensitivity, cutaneous absorption, opacity and permeability of the bovine cornea, phototoxicity in vitro, chromosomal mutagenesis, repeated dose dermal toxicity, and stability study. It is intended that the formulation meets the necessary requirements for registration with ANVISA. (AU)