Banca de DEFESA: EDIELEN FRANÇA DOS SANTOS

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : EDIELEN FRANÇA DOS SANTOS
DATE: 10/07/2024
TIME: 09:00
LOCAL: Programa de Pós-Graduação em Ciência de Materiais
TITLE:

DESIGN OF A TRANSDERMAL DRUG DELIVERY SYSTEM BASED ON MICRONEEDLES OBTAINED BY 3D PRINTING

KEY WORDS:

Microneedles. Biomaterials. 3D printing. biocompatible resin. drug delivery systems.

PAGES: 137
BIG AREA: Outra
AREA: Multidisciplinar
SUMMARY:

Microneedles present themselves as attractive devices for transdermal drug delivery due to their micrometer-scale dimensions, allowing penetration through the skin in a minimally invasive manner without activating nerve endings. A promising approach for manufacturing microneedles is additive manufacturing, particularly stereolithography, which enables the creation of simple, customizable, and low-cost prototypes. In light of these aspects, the present work aimed to develop microneedles as a new transdermal delivery system using 3D printing technology based on masked stereolithography (MSLA) through two routes: I) Employing a two-step mold manufacturing method, "master and micromolding," the master microneedles were designed and 3D printed, followed by micromolding in thermoplastic adhesive and production of polymeric microneedles made of sodium alginate and polymethylmethacrylate (PMMA); II) Synthesis of monomers based on cyclohexanedimethanol, glycerol, phloroglucinol, and soybean oil methacrylates for the production of biofunctional resins used in the direct manufacture of microneedles. The micro-molded alginate microneedle matrices exhibited insufficient fracture toughness, requiring additives to improve mechanical strength. The PMMA microneedle matrices, analyzed by optical microscopy and scanning electron microscopy, showed satisfactory sub-millimeter dimensions with good straightness and a high degree of detail. However, they presented low tip resolution and porous surface structures; the latter being a critical factor in the adsorption process of the drugs dexamethasone and quercetin. The PMMA matrix adsorption assay for quercetin showed temperature dependence, while for dexamethasone, adsorption seemed to be only time-dependent. These characteristics indicate that micromolded microneedles show promising results as potential drug delivery systems. The second route involved the synthesis of methacrylate monomers, characterized by nuclear magnetic resonance and infrared spectroscopy to confirm the structures of all intended resin monomers. By combining these monomers, it was possible to develop three resin prototypes with suitable viscosities (below 3 Pa.s) for printing, characterized by rotational rheology. The resins were used to print conical microneedle matrices (10x10), whose dimensions were evaluated by scanning electron microscopy, showing heights of approximately 655.0 ±1.9 µm (MA 1), 663.0 ±1.2 µm (MA 6), and 660 ±1.0 µm (MA 7). These microneedles also underwent thorough mechanical and thermal characterization. Depth analysis of microperforations in Parafilm "M" and pig skin was performed using OCT and histological sections, demonstrating successful penetration through the stratum corneum and epidermal layers into the superficial dermal layer (1.5-4 mm thick) without affecting nerve endings. Cytocompatibility tests confirmed the biocompatibility of the microneedles. This work highlights the production of new biocompatible resins developed for printable drug delivery systems, emphasizing microneedles and paving the way for other highperformance implants for stereolithography applications.

COMMITTEE MEMBERS:
Interna - 1356402 - CAROLINA LIPPARELLI MORELLI
Interno - 2457389 - EDUARDO PADRON HERNANDEZ
Externa à Instituição - ELIBE SILVA SOUZA - UFPE
Externo à Instituição - EMANOEL LAURERTAN TAVARES FRANÇA - UFPE
Presidente - 1354207 - SEVERINO ALVES JUNIOR