Fabrication of Ultra-sharp Polymeric Microneedles via Computer Numerical Control (CNC) Micromachining and Micromolding

Summary

This article introduces a simple, straightforward, and innovative fabrication protocol for producing polymeric microneedles with exceptionally sharp tips through micromolding from master molds created via Computer Numerical Control (CNC) milling. The developed system is cost-effective, easy to construct, and capable of producing microneedles with exceptional sharpness for enhanced penetration, thereby improving delivery performance.

Abstract

Microneedles have recently gained recognition as a promising method in transdermal drug delivery owing to their minimally invasive, painless nature, and they can be flexibly engineered through geometric modifications to meet specific therapeutic requirements. Hence, this study aims to develop microneedle master molds utilizing Computer Numerical Control (CNC) milling technology to create polymeric microneedles with diverse degrees of sharpness to enhance therapeutic efficacy. Previously, our team successfully optimized two critical machining parameters, feed rate, and ramp angle, while analyzing their influence on the obtained needles. Hence, this article presents a comprehensive set of experimental protocols for fabricating and evaluating the performance of the polymeric-based model needles. Furthermore, this work also provides representative results to demonstrate the reproducibility and therapeutic efficacy of the sample needles. Our research team anticipates that this straightforward protocol will enable researchers to create cost-effective, high-precision microneedles, thereby advancing microneedle technology for further biomedical applications, particularly during the pandemic.

Introduction

Microneedles have emerged as a promising candidate for drug delivery in recent years due to their painless, self-administrable nature while circumventing the first-pass liver metabolism¹. Microneedles have captured much attention in many biomedical applications (e.g., vaccination, cancer treatment, diagnostics, cosmetics), which require precise, minimally invasive delivery of therapeutic agents or other substances into the skin or underlying tissues, enhancing treatment efficacy with limited adverse effects².

Depending on the intended applications, microneedles can be made in many forms (i.e.,....

Protocol

The reagents, equipment, and software used for this study are listed in the Table of Materials.

1. Fabrication of polymethyl methacrylate (PMMA)-based microneedle master molds

1. Microneedle master mold design
   NOTE: The microneedle master mold design was conducted using Fusion 360 (Autodesk, USA, education license) (see Table of Materials).
   1. Open the software in the Design environment and create a new sketch.
   2. Draw a box using the Extrude function.
   3. Generate stepped cavities using the Extrude Cut

Results

This study introduces a protocol for fabricating microneedle master molds, which are engineered to achieve exceptionally sharp microneedles using CNC micromilling. To examine data about tip sharpness, readers are encouraged to refer to the previous publication⁵. Figure 1 shows the schematic view of the microneedle master mold design with its dimensions. Figure 2 illustrates the transformation of the schematic design into milling instructi.......

Discussion

This study developed a unique experimental protocol to fabricate master molds to produce polymeric microneedles with excellent sharpness through CNC micromachining and micromolding. Primarily, this approach includes integrating a schematic design with the fabrication of a master mold via CNC milling, followed by a series of micromolding processes to create microneedle patches. For a long time, micromolding has been widely used due to its ability to produce intricate, reproducible microstructures with high accura.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
3-axis machining center	Tormach PCNC 1100		CNC mill for cutting materials
Automatic Needle Injection Configuration	Self-developed		Mechanical measurement software
Distilled water	Cole-Parmer WS-200 Series Stuart Water Stills
Fusion 360 software, Education version	Autodesk, USA	Design software (https://www.autodesk.com/asean/products/fusion-360/overview?term=1-YEAR&tab=subscription)
ImageJ software	National Institutes of Health, USA		Image analysis
Polydimethylsiloxane	SYLGARD 184 Silicone Elastomer Kit	1330-20-7	Used for negative molds
Polymethyl methacrylate			Used for master molds
Polyvinyl alcohol	Sigma Aldrich, USA	9003-39-8	Microneedle material
Polyvinyl pyrrolidone	Sigma Aldrich, USA	9002-89-5	Microneedle material
Rhodamine B	Sigma Aldrich, USA	83689-1G	Model drug
Water-soluble chitosan			Microneedle material