Hydrogel Microneedles with Programmed Mesophase Transitions for Controlled Drug Delivery.

Microneedle-based drug delivery offers an attractive and minimally invasive administration route to deliver therapeutic agents through the skin by bypassing the stratum corneum, the main skin barrier. Recently, hydrogel-based microneedles have gained prominence for their exceptional ability to precisely control the release of their drug cargo. In this study, we investigated the feasibility of fabricating microneedles from triblock amphiphiles with linear poly(ethylene glycol) (PEG) as the hydrophilic middle block and two dendritic side-blocks with enzyme-cleavable hydrophobic end-groups. Due to the poor formation and brittleness of microneedles made from the neat amphiphile, we added a sodium alginate base layer and tested different polymeric excipients to enhance the mechanical strength of the microneedles. Following optimization, microneedles based on triblock amphiphiles were successfully fabricated and exhibited favorable insertion efficiency and low height reduction percentage when tested in Parafilm as a skin-simulant model. When tested against static forces ranging from 50 to 1000 g (4.9-98 mN/needle), the microneedles showed adequate mechanical strength with no fractures or broken segments. In buffer solution, the solid microneedles swelled into a hydrogel within about 30 s, followed by their rapid disintegration into small hydrogel particles. These hydrogel particles could undergo slow enzymatic degradation to soluble polymers. In vitro release study of dexamethasone (DEX), as a steroid model drug, showed first-order drug release, with 90% released within 6 days. Eventually, DEX-loaded MNs were subjected to an insertion test using chicken skin and showed full penetration. This study demonstrates the feasibility of programming hydrogel-forming microneedles to undergo several mesophase transitions and their potential application as a delivery system for self-administration, increased patient compliance, improved efficacy, and sustained drug release.

Rapidly Dissolving Microneedles for the Delivery of Steroid-Loaded Nanoparticles Intended for the Treatment of Inflammatory Skin Diseases.

Drug delivery through the skin has immense advantages compared to other routes of administration and offers an optimal way to treat inflammatory skin diseases, where corticosteroids are the cornerstone of topical therapy. Still, their therapeutic efficiency is limited due to inadequate skin permeability, potential side effects, and reduced patient compliance. To overcome these drawbacks, we propose a drug delivery system consisting of dexamethasone (DEX)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) incorporated in sodium alginate (SA) microneedles (MNs) as a minimally invasive dosage form for controlled drug release. Drug-loaded PLGA NPs were prepared by a nanoprecipitation method with a high encapsulation yield. They exhibited a controlled release pattern over 120 h. A modified vacuum-deposition micromolding method was used to load the obtained DEX-NPs into the tips of dissolving MNs. The NP-MNs showed improved insertion capabilities into the skin-simulant parafilm model and enhanced mechanical strength when tested against different static forces compared to their counterparts (SA-MNs). The results of an MN dissolution study following application to ex vivo chicken skin and agarose gel indicate that the NP-loaded segments of MNs dissolve within 15 s, in which the NPs are released into the skin. Taken together, the incorporation of DEX-NPs into SA-MNs could be a promising approach to bypass the limitations of conventional topical treatment of skin diseases, allowing for self-administration, increased patient compliance, and controlled drug release.

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

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.