Novel lipid nanovesicle-loaded dissolving microarray patches for fenretinide in breast cancer chemoprevention

Author(s)

Apolinario, Alexsandra Conceicao ; Naser, Yara A. ; Volpe-Zanutto, Fabiana ; Vora, Lalitkumar K. ; Sabri, Akmal H. ; Li, Mingshan ; Hutton, Aaron R. J. ; McCarthy, Helen O. ; Lopes, Luciana B. ; Donnelly, Ryan F.

• Document type: Journal article
• Source: JOURNAL OF CONTROLLED RELEASE; v. 374, p. 13-pg., 2024-08-10.

Abstract

The retinoid fenretinide (FENR) is a promising compound for preventing breast cancer recurrence but faces challenges due to poor solubility and low bioavailability. This study explores the development of dissolving microneedles (MNs) containing FENR-loaded ethosomes for minimally invasive breast cancer chemoprevention, aiming to enhance local drug distribution. Ethosomes were formulated using ethanol, propylene glycol, soya lecithin, water, and polysorbate 80 micelles. MNs were created from poly(vinyl alcohol) and poly(vinylpyrrolidone) hydrogels by adding polymer powder directly into ethosomes suspensions, reducing manufacturing time and cost. Two methods were used to load ethosomes into high-density moulds: 1) only in the needle area, and 2) in both the needle area and baseplate. Dynamic light scattering confirmed nanostructures in the hydrogels and MNs. Micelle-based ethosomes dissolved MNs in 15 min, compared to 30 min for other MNs. Skin deposition studies showed greater drug deposition (up to 10 mu g/patch) and enhanced skin permeation of FENR (up to 40 mu g) with Method 2. In-vivo studies in rats demonstrated that oral administration resulted in plasma FENR levels below 10 ng/g in the first three hours, whereas MN administration delayed delivery, reaching a maximum plasma concentration of 52 ng/g at 48 h. Skin deposition of FENR from MNs decreased from 3 mu g/g on day 1 to <0.3 <mu>g/g by the last day. This study indicates that MNs are a potential minimally invasive dosage form for delivering FENR, offering a new approach for breast cancer chemoprevention. (AU)

• FAPESP's process: 18/13877-1 - Nanocarriers for localized treatment and chemoprevention of breast tumors
• Grantee: Luciana Biagini Lopes
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
• FAPESP's process: 21/06919-2 - Nanoengineered microneedle arrays for enhanced and sustained delivery of the poorly soluble drug fenretinide
• Grantee: Alexsandra Conceição Apolinário
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 18/14375-0 - Nanotechnology-based topical delivery systems for breast cancer chemoprevention
• Grantee: Alexsandra Conceição Apolinário
• Support Opportunities: Scholarships in Brazil - Post-Doctoral