Upconverting Nanoparticle-Loaded Microneedles for Near-Infrared Responsive Delivery of Gonadotropins to Increase Success of In Vitro Fertilization - research article

Sep 28, 2026

Uploaded by Kurz

In vitro fertilization relies on repeated, time-critical gonadotropin injections, which create pain and stress and can compromise outcomes through timing or dosing variability. This study develops a hydrogel microneedle (MN) patch incorporating upconverting nanoparticles coated with light-breakable mesoporous silica (UCNP@LBMS) to trigger near-infrared (NIR) light–responsive release of the gonadotropin leuprolide. In rats, a 5 min NIR pulse at 2 W/cm² significantly increases leuprolide release in skin and plasma, with MN length influencing bioavailability. The UCNPs remain within the MN patch, and the platform is positioned as a painless automated alternative for other repeated, hypodermic, time-sensitive regimens.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages16

Reading Time40 min

AccessFree to download

Introduction

Materials and microneedle drug delivery constraints

NIR-responsive strategy and UCNP@LBMS design

Experimental evaluation and implications

RESEARCH ARTICLE [www.small-journal.com](www.small-journal.com) Upconverting Nanoparticle-Loaded Microneedles for Near-Infrared Responsive Delivery of Gonadotropins to Increase Success of In Vitro Fertilization Vivienne Tam, Rusvir Trana, Alfonso Nieto-Arguello, Ore-Oluwa Olasubulumi, Samuel Babity, Artiom Skripka, Fiorenzo Vetrone, Davide Brambilla,* and Marta Cerruti* In vitro fertilization (IVF) requires repeated bolus injections of gonadotropins at precise times, making it a painful and stressful experience for women. Polymeric microneedles (MNs) present a painless alternative to hypodermic needles, but controlling the release of drugs through MNs remains a challenge. Here, we report the development of a hydrogel MN patch integrated with upconverting nanoparticles coated with light-breakable mesoporous silica (UCNP@LBMS) that releases the IVF gonadotropin, leuprolide, in response to near-infrared (NIR) light, while retaining the UCNPs within the MN patch. In rats, a 5 min NIR pulse of 2 W cm−2 results in asigniﬁcant increase in leuprolide release in both skin and plasma, with MN length playing an important role in drug bioavailability. Beyond IVF, UCNP-integrated MN patches oﬀer a painless, automated alternative in any application that requires daily, repeated, time-sensitive hypodermic needle injections, such as diabetes or multiple sclerosis. inject themselves daily with gonadotropins for 2 weeks to increase the number ofoocytes available, before the oocytes are retrieved, fertilized, and implanted in the patient. [3] The COH phase, in particular, imposes a great physical and psychological burden on women due to its time-sensitive nature and use of hypodermic needles for subcutaneous injections. [2] In fact, the burden of COH is cited as the primary reason for withdrawal from treatment. [4] In addition, the possible variability in timing or dosage with hypodermic needle self-administration could severely hinder the success rate of the procedure, further increasing the stress associated with a treatment priced at $15,000 - $20,000 CAD/cycle. [5] Painless transdermal microneedles (MNs) deliver drugs in a minimally 1. Introduction One in every 6 couples struggles with infertility,[1] a number that is expected to grow due to rising maternal age at ﬁrst birth. [2] Asa result, many are turning to in vitro fertilization (IVF) as an alternate means of reproduction. The IVF process consists of controlled ovarian hyperstimulation (COH), during which women invasive manner by penetrating the stratum corneum without activating the pain response from nerves located deeper in the dermis. [6,7] Of the materials used to manufacture MNs (e.g., glass, silicon), certain polymers are preferred as they elicit no immunogenic response, degrade into non-toxic products ina physiological environment, and have suﬃcient mechanical strength to penetrate skin.[8–10] Typically, polymeric MNs rapidly V. Tam, M. Cerruti Mining and Materials Engineering McGill University 3610 Rue University, Montreal, Quebec H3A 0C5, Canada [E-mail:](E-mail: marta.cerruti@mcgill.ca)[ marta.cerruti@mcgill.ca](E-mail: marta.cerruti@mcgill.ca) R. Trana, O.-O. Olasubulumi Bioengineering McGill University 3480 Rue University, Montreal, Quebec H3A 0E9, Canada The ORCID identiﬁcation number(s) for the author(s) of this article can be found under [https://doi.org/10.1002/smll.202513138](https://doi.org/10.1002/smll.202513138) © 2025 The Author(s) . Small published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modiﬁcations or adaptations are made. DOI: 10.1002/smll.202513138 A. Nieto-Arguello, S. Babity, D. Brambilla Faculty of Pharmacy Université de Montreal 2940 chemin de Polytechnique, Montreal, Quebec H3T 1J4, Canada E

FAQs

Why are repeated gonadotropin injections a problem in IVF?

IVF typically requires repeated, precisely timed injections of gonadotropins, which can be painful and stressful. Timing or dosage variability with self-administration may also hinder success rates.

How does the microneedle patch release leuprolide in response to light?

The hydrogel microneedle patch integrates UCNP@LBMS, which respond to near-infrared light to enable release of the IVF gonadotropin leuprolide. The UCNPs remain retained within the patch while release occurs.

What do the rat results show after NIR exposure?

A 5-minute NIR pulse at 2 W/cm² significantly increases leuprolide release in both skin and plasma. The microneedle length also plays an important role in drug bioavailability.

Sep 28, 2026

Uploaded by Kurz