Bimodal Dissolving Microneedles with Nanoparticle Coating and Encapsulation for Extended Dual-Drug Delivery.

Area of Science:

• Biomaterials Science
• Nanotechnology
• Pharmacology

Background:

• Microneedle (MN) platforms face challenges in co-delivering multiple drugs due to limited capacity and sustained release requirements.
• Osteoarthritis treatment necessitates effective, sustained delivery of anti-inflammatory drugs like diclofenac (DCF) and dexamethasone (DSP).

Purpose of the Study:

• To develop and evaluate a bimodal coated-dissolving microneedle (DMN) patch for the extended co-delivery of diclofenac and dexamethasone nanoparticles.
• To assess the transdermal penetration, release kinetics, and in vivo pharmacokinetics of dual-drug loaded DMNs for osteoarthritis therapy.

Main Methods:

• Fabrication of DMNs with DCF nanoparticles in the tips and DSP-PLGA nanosuspensions as a coating.
• Ex vivo skin penetration studies using neonatal porcine skin to evaluate DMN efficacy.
• In vivo pharmacokinetic studies in rats to determine drug plasma levels, bioavailability, and tissue distribution.

Main Results:

• DMNs achieved >90% penetration into the stratum corneum, delivering DCF and DSP effectively.
• In vivo studies showed sustained DCF plasma levels for 72 h (13.0 h half-life, 80.3% bioavailability) and biphasic DSP release peaking at 24-30 h (63.9% bioavailability).
• High drug concentrations were maintained in skin and paw tissues for 72 h, indicating prolonged local therapeutic effects.

Conclusions:

• Bimodal DMNs offer a high-loading, sustained-release platform for minimally invasive dual-drug therapy.
• This approach optimizes osteoarthritis treatment by enhancing patient compliance through a patient-friendly, single-patch delivery system.
• The developed DMN technology shows significant potential for improving localized drug delivery and therapeutic outcomes.