Innovative HPMC/PVP K90 Dissolving Microneedles Incorporating Tacrolimus-Loaded Cubosomes: A Novel Strategy for...

Area of Science:

• Ophthalmology
• Nanotechnology
• Pharmaceutics

Background:

• Allergic conjunctivitis (AC) is a prevalent ocular inflammatory condition.
• Tacrolimus (TCR), an effective calcineurin inhibitor, suffers from poor solubility and bioavailability for ocular use.
• Developing advanced drug delivery systems is crucial for improving TCR's therapeutic efficacy in AC.

Purpose of the Study:

• To formulate and characterize tacrolimus-loaded cubosomes (TCR-Cubs).
• To incorporate TCR-Cubs into dissolving microneedles (MNs) for enhanced ocular delivery.
• To evaluate the efficacy of the TCR-Cubs-loaded MNs in a rabbit model of allergic conjunctivitis.

Main Methods:

• TCR-Cubs were prepared using glyceryl monooleate and poloxamer 407, optimized via Box-Behnken design.
• Dissolving microneedles were fabricated using micro molding with HPMC/PVP K90.
• The system's performance was assessed through in vitro, ex vivo, and in vivo evaluations in a rabbit AC model.

Main Results:

• Optimized TCR-Cubs showed small particle size (210 nm), high entrapment efficiency (>93%), and sustained release (>75% over 24h).
• Microneedles exhibited good mechanical stability and high penetration efficiency (>85%).
• In vivo studies demonstrated significant reduction in inflammatory markers (50-75%) and corneal drug flux enhancement (2-3 fold) without irritation.

Conclusions:

• The developed TCR-Cubs-loaded dissolving MNs represent a promising non-invasive platform for enhanced ocular drug delivery.
• This dual-delivery system offers superior anti-inflammatory efficacy for treating allergic conjunctivitis.
• The formulation overcomes tacrolimus's bioavailability limitations for effective ocular therapy.