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

Alexsandra Apolinário; Yara Naser; Fabiana Volpe-Zanutto; Lalitkumar K. Vora; Akmal Hidayat Bin Sabri; Mingshan Li; Aaron Hutton; Helen McCarthy; Luciana Lopes; Ryan F. Donnelly

doi:10.1016/j.jconrel.2024.07.080

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

Alexsandra Apolinário, Yara Naser, Fabiana Volpe-Zanutto, Lalitkumar K. Vora, Akmal Hidayat Bin Sabri, Mingshan Li, Aaron Hutton, Helen McCarthy, Luciana Lopes, Ryan F. Donnelly

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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 μg/patch) and enhanced skin permeation of FENR (up to 40 μg)
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 μg/g on day 1 to
<0.3 μg/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.

Original language	English
Pages (from-to)	76-88
Number of pages	13
Journal	Journal of Controlled Release
Volume	374
Early online date	10 Aug 2024
DOIs	https://doi.org/10.1016/j.jconrel.2024.07.080
Publication status	Published online - 10 Aug 2024

Bibliographical note

Data Access Statement

Data will be made available on request.

Keywords

Ethosomes
Nanovesicles
Micromolding
Microarray patches
Local transdermal therapy
Breast cancer chemoprevention

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jconrel.2024.07.080Licence: CC BY

1-s2.0-S0168365924005388-mainFinal published version, 6.19 MBLicence: CC BY

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Apolinário, A., Naser, Y., Volpe-Zanutto, F., Vora, L. K., Sabri, A. H. B., Li, M., Hutton, A., McCarthy, H., Lopes, L., & Donnelly, R. F. (2024). Novel lipid nanovesicle-loaded dissolving microarray patches for fenretinide in breast cancer chemoprevention. Journal of Controlled Release, 374, 76-88. Advance online publication. https://doi.org/10.1016/j.jconrel.2024.07.080

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title = "Novel lipid nanovesicle-loaded dissolving microarray patches for fenretinide in breast cancer chemoprevention",

abstract = "The retinoid fenretinide (FENR) is a promising compound for preventing breast cancer recurrence but faceschallenges due to poor solubility and low bioavailability. This study explores the development of dissolvingmicroneedles (MNs) containing FENR-loaded ethosomes for minimally invasive breast cancer chemoprevention,aiming to enhance local drug distribution. Ethosomes were formulated using ethanol, propylene glycol, soyalecithin, 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 manufacturingtime 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 hydrogelsand MNs. Micelle-based ethosomes dissolved MNs in 15 min, compared to 30 min for other MNs. Skin depositionstudies showed greater drug deposition (up to 10 μg/patch) and enhanced skin permeation of FENR (up to 40 μg)with Method 2. In-vivo studies in rats demonstrated that oral administration resulted in plasma FENR levelsbelow 10 ng/g in the first three hours, whereas MN administration delayed delivery, reaching a maximumplasma concentration of 52 ng/g at 48 h. Skin deposition of FENR from MNs decreased from 3 μg/g on day 1 to<0.3 μg/g by the last day. This study indicates that MNs are a potential minimally invasive dosage form fordelivering FENR, offering a new approach for breast cancer chemoprevention.",

keywords = "Ethosomes, Nanovesicles, Micromolding, Microarray patches, Local transdermal therapy, Breast cancer chemoprevention",

author = "Alexsandra Apolin{\'a}rio and Yara Naser and Fabiana Volpe-Zanutto and Vora, {Lalitkumar K.} and Sabri, {Akmal Hidayat Bin} and Mingshan Li and Aaron Hutton and Helen McCarthy and Luciana Lopes and Donnelly, {Ryan F.}",

year = "2024",

month = aug,

day = "10",

doi = "10.1016/j.jconrel.2024.07.080",

language = "English",

volume = "374",

pages = "76--88",

journal = "Journal of Controlled Release",

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TY - JOUR

T1 - Novel lipid nanovesicle-loaded dissolving microarray patches for fenretinide in breast cancer chemoprevention

AU - Apolinário, Alexsandra

AU - Naser, Yara

AU - Volpe-Zanutto, Fabiana

AU - Vora, Lalitkumar K.

AU - Sabri, Akmal Hidayat Bin

AU - Li, Mingshan

AU - Hutton, Aaron

AU - McCarthy, Helen

AU - Lopes, Luciana

AU - Donnelly, Ryan F.

PY - 2024/8/10

Y1 - 2024/8/10

N2 - The retinoid fenretinide (FENR) is a promising compound for preventing breast cancer recurrence but faceschallenges due to poor solubility and low bioavailability. This study explores the development of dissolvingmicroneedles (MNs) containing FENR-loaded ethosomes for minimally invasive breast cancer chemoprevention,aiming to enhance local drug distribution. Ethosomes were formulated using ethanol, propylene glycol, soyalecithin, 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 manufacturingtime 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 hydrogelsand MNs. Micelle-based ethosomes dissolved MNs in 15 min, compared to 30 min for other MNs. Skin depositionstudies showed greater drug deposition (up to 10 μg/patch) and enhanced skin permeation of FENR (up to 40 μg)with Method 2. In-vivo studies in rats demonstrated that oral administration resulted in plasma FENR levelsbelow 10 ng/g in the first three hours, whereas MN administration delayed delivery, reaching a maximumplasma concentration of 52 ng/g at 48 h. Skin deposition of FENR from MNs decreased from 3 μg/g on day 1 to<0.3 μg/g by the last day. This study indicates that MNs are a potential minimally invasive dosage form fordelivering FENR, offering a new approach for breast cancer chemoprevention.

AB - The retinoid fenretinide (FENR) is a promising compound for preventing breast cancer recurrence but faceschallenges due to poor solubility and low bioavailability. This study explores the development of dissolvingmicroneedles (MNs) containing FENR-loaded ethosomes for minimally invasive breast cancer chemoprevention,aiming to enhance local drug distribution. Ethosomes were formulated using ethanol, propylene glycol, soyalecithin, 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 manufacturingtime 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 hydrogelsand MNs. Micelle-based ethosomes dissolved MNs in 15 min, compared to 30 min for other MNs. Skin depositionstudies showed greater drug deposition (up to 10 μg/patch) and enhanced skin permeation of FENR (up to 40 μg)with Method 2. In-vivo studies in rats demonstrated that oral administration resulted in plasma FENR levelsbelow 10 ng/g in the first three hours, whereas MN administration delayed delivery, reaching a maximumplasma concentration of 52 ng/g at 48 h. Skin deposition of FENR from MNs decreased from 3 μg/g on day 1 to<0.3 μg/g by the last day. This study indicates that MNs are a potential minimally invasive dosage form fordelivering FENR, offering a new approach for breast cancer chemoprevention.

KW - Ethosomes

KW - Nanovesicles

KW - Micromolding

KW - Microarray patches

KW - Local transdermal therapy

KW - Breast cancer chemoprevention

UR - https://www.sciencedirect.com/science/article/pii/S0168365924005388?via%3Dihub

UR - http://www.scopus.com/inward/record.url?scp=85200804464&partnerID=8YFLogxK

U2 - 10.1016/j.jconrel.2024.07.080

DO - 10.1016/j.jconrel.2024.07.080

M3 - Article

C2 - 39111598

SN - 0168-3659

VL - 374

SP - 76

EP - 88

JO - Journal of Controlled Release

JF - Journal of Controlled Release

ER -

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

Abstract

Bibliographical note

Data Access Statement

Keywords

UN SDGs

Access to Document

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