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Published on: June 1, 2012
Thermosensitive hydrogel microneedles for controlled transdermal drug delivery
Jun You Li1, Yun Hao Feng1, Yu Ting He1
1State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing 10029, China; Beijing Laboratory of Biomedical Materials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, PR China.
This study developed temperature-sensitive hydrogel microneedles (MNs) using gelatin-grafted poly(N-isopropylacrylamide) (PNIPAm) for controlled drug delivery. The novel system offers painless, noninvasive administration and effective insulin release in diabetic mice.
Area of Science:
- Biomaterials Science
- Drug Delivery Systems
- Polymer Chemistry
Background:
- Poly(N-isopropylacrylamide) (PNIPAm) exhibits thermo-reversible sol-gel transitions, enabling temperature-controlled material properties.
- Hydrogel microneedles (MNs) offer minimally invasive drug delivery, but controlling release kinetics and mechanical stability remains challenging.
- Existing MN fabrication methods may involve toxic crosslinkers and can lead to drug crystallization, hindering efficacy.
Purpose of the Study:
- To fabricate physically entangled hydrogel microneedles using gelatin grafted with carboxylic end-capped PNIPAm (gelatin-g-PNIPAm) for controlled drug release.
- To enhance microneedle mechanical strength and reduce application time by developing a rapidly separating microneedle system (RS-GP-MNs).
- To evaluate the drug release control and in vivo efficacy of the RS-GP-MNs for noninvasive drug administration.
Main Methods:
- Grafting carboxylic end-capped PNIPAm onto gelatin to create a thermo-sensitive matrix material.
- Fabrication of hydrogel microneedles (MNs) with reduced drug crystallization due to thermo-reversible sol-gel transition.
- Development of a rapidly separating microneedle system (RS-GP-MNs) by mounting hydrogel MNs onto solid MNs for enhanced mechanical strength and rapid insertion.
Main Results:
- The RS-GP-MNs demonstrated a suitable lower critical solution temperature and adequate crosslinking speed for practical applications.
- The system efficiently delivered drug-loaded MNs into the skin within seconds and provided controlled drug release.
- In diabetic mice, RS-GP-MNs effectively controlled blood glucose levels via insulin release, outperforming unmodified gelatin MNs.
Conclusions:
- The developed RS-GP-MNs system utilizes thermosensitive hydrogel properties for controlled, reversible drug release at body temperature.
- This fabrication method avoids toxic molecular crosslinkers, offering a safer alternative for hydrogel microneedle production.
- The RS-GP-MNs system shows significant potential for noninvasive, painless administration of hydrophilic drugs and peptides, addressing challenges in frequent dosing.
