Attanasio, Alessandro (2024) Versatile Microparticle-Based Microneedles Platform for Intradermal Delivery. [Tesi di dottorato]

Anteprima

Testo Attanasio_Alessandro_36.pdf Download (4MB) | Anteprima

Abstract

Transdermal delivery complements the list of administration routes alongside oral and parenteral ones, but only a limited class of active principles may be absorbed through the skin passively. Microneedles (MNs) represent an ideal delivery platform capable of facing several challenges in the transdermal administration field. They permit to access to the intradermal and transdermal routes without reaching nerve endings, and enabling molecules with molecular mass > 500 Da to pass through the stratum corneum, the natural barrier of the human organism. MNs constitute an attractive technology within drug delivery field since they can be used to deliver substances, also overcoming some of the main limitations of conventional hypodermic needles which require administration by trained healthcare personnel and risk of diseases transmission. Moreover, MNs offer an ideal solution for the patient compliance by mitigating pain and needle-phobia discomfort. Despite being introduced over twenty years ago, there are still challenges in achieving the desired characteristics. Among different MNs categories Polymer MNs are interesting for easy scale up, low cost and possibility to control drug release depending on their properties. However, they are typically characterized by low drug loading. limiting the number of applications, and incomplete penetration in the skin, making the delivery less effective and not reproducible. In addition, the stability of labile molecules is often affected by MNs fabrication process. The current work aims to design and realize a MN-based technology patch able to provide complete indentation, namely implantation, and a low invasive fabrication procedure allowing the encapsulation of different drugs in an active form and its sustained release. The proposed technological platform is constituted by a bi-compartmental array of microparticle-based MNs where a fast dissolvable tip, along with slow release polymer microparticles (μPs) are assembled together and integrated onto polymethyl methacrylate (PMMA) pillars. The combination of PLGA μPs with microneedle technology, makes μPs-based MNs versatile for a wide range of implementations. Based on a renewed fabrication process, the versatility of μPs-based MNs was explored in different contexts to evaluate the robustness of the platform. Based on the achieved results, microparticle-based MNs are under investigation for mRNA delivery currently.

Downloads

Actions (login required)

Modifica documento