Evaluation of the Feasibility of Transdermal Delivery of Neratinib (NB) Loaded Microneedles to Treat Breast Cancer

Abstract

Background: Breast cancer is the world’s second-largest leading cause of death in women. Targeting highly localized tumors using transdermal microneedle drug delivery can be highly advantageous in treating breast cancer.Aim: The present study evaluates the feasibility of transdermal delivery of promising chemo preventive agent tyrosine kinase inhibitor Neratinib (NB) and physicochemical properties through breast skin and mammary papilla.Materials and Methods: The Microneedles (MNs) were fabricated by photo-polymerization method using PEGDA as a biopolymer and TPO as a photo initiator. Optimized (F3) MNs were characterized for stereomicroscopy, Scanning Electron Microscopy (SEM), and mechanical testing. The in vitro permeation studies were carried out on a vertical Franz diffusion cell using porcine skin.Results: The cytotoxicity of the optimized formulation on MCF-7 cell lines was carried out using an MTT assay. The FT-IR compatibility studies showed no chemical interaction between drug and excipients used, and an increase in NB solubility decreased the epidermal/vehicle partition coefficient and vice-versa. Microneedles’ pitch and total base diameter were evaluated and found acceptable for the study. The mechanical test confirmed that >30% of the needles penetrated the 3rd and <30% penetrated the 4th layers. The in vitro permeation studies showed that in breast skin and mammary papilla, the highest skin retention of NB was observed with 64% alcohol compared to 32 and 48% alcohol. Microneedles with 32% alcohol significantly increased the permeation of NB, and microneedles increased the cumulative amount of NB permeated through breast skin by 2.9-fold and decreased the lag time by 3.6-fold. However, there was no significant difference in the skin retention amount after pretreatment with microneedles.Conclusion: The results showed that the neratinib-loaded microneedles can be used as an effective transdermal delivery for preventing and treating breast cancer.

Keywords: Breast cancer; Microneedles; Tyrosine kinase inhibitors; Transdermal delivery; Neratinib