Preparation and characterization of flexible furosemide-loaded biodegradable microneedles for intradermal drug delivery

Abstract

Transdermal drug delivery systems are a useful and minimally invasive alternative to other drug administration routes. Biodegradable polymeric microneedles (MNs) are widely used in controlled–release drug delivery due to their tunable properties and ease of patient self-administration. Polylactic-co-glycolic acid (PLGA) is often used for sustained drug release owing to special intrinsic properties including biocompatibility and biodegradability, which offer excellent applicability in preparing MNs. Congestive heart failure (CHF) is characterized by fluid overload during acute exacerbation, necessitating frequent patient hospitalization for continuous intravenous (i.v.) diuretic therapy. In the present study, we incorporated furosemide (FUR) as a model drug into flexible PLGA MN skin patches for potential intradermal delivery to overcome the limitations associated with i.v. diuresis. The MNs were fabricated by a casting-mold technique and consisted of two main parts, PLGA needle tips loaded with varying concentrations of FUR and a flexible backing layer comprising sodium alginate and glycerol. MN formulations were characterized by SEM and exhibited a uniform pyramidal shape. The measured surface pH of all samples suggested that no skin irritation is expected upon application. High encapsulation efficiency was obtained for FUR-MN formulations in which a decrease was noted as the FUR/PLGA ratio decreased. Drug loading content ranged from 19.1 ± 1% to 28.9 ± 1.4%. Successful insertion of MNs into a Parafilm® skin simulant model suggested that MNs will easily penetrate the skin's outermost layer, the stratum corneum, and will permit intradermal delivery of FUR. The MNs were further characterized by analytical methods. Finally, the MNs exhibited an initial burst release followed by a sustained release of FUR. Self-administered FUR-MNs can open new avenues to overcome i.v. drip limitations and increase patient compliance.