Nano-PhotoCrystals (Photosensitive Nanocrystals) of Aloe Emodin Combined with Dissolving Microneedles for Dual Smart Targeting of Acute Bacterial Skin and Soft Tissue Infections

Acute bacterial skin and soft tissue infections (ABSSTIs) are often treated with antibiotics, facing challenges with off-target toxicity and limited tissue penetration, with inadequate treatment escalating into serious conditions requiring hospitalization. Photodynamic antibacterial therapy (PACT), employing natural photosensitizers (PS), presents a promising alternative but is limited by poor water solubility, with modification strategies restricted by limited loading efficiency and drug release due to quenching effects (e.g., liposomes). To this end, this study explores the utilization of a matrix-free system, introducing the novel preparation of photosensitive nanocrystals (i.e., nanosized photosensitizers) referred to as nano-PhotoCrystals, derived from aloe emodin (AE), an anthraquinone naturally found in <i>Aloe vera</i>. Both nanosized and micronized AE PhotoCrystals were produced, with AE nanosized PhotoCrystals (N-PCs) prepared via bead-milling, and micronized AE PhotoCrystals (M-PCs) prepared by simple dispersion in surfactant solution were integrated with dissolving microneedles (MNs), to permit improved aqueous solubility and targeted dermal delivery. All formulations prepared were characterized for physicochemical properties, stability, and transdermal permeation and dermal deposition. It was found that N-PCs, with a mean particle size of approximately 200 nm, increased drug deposition in skin layers, achieving about 50 μg/cm³ in the dermis, while M-PCs, ∼40 μm in size, achieved less than 12 μg/cm³. Additionally, the incorporation of AE N-PCs within MNs further improved dermal drug delivery, demonstrating a well-improved deposition profile (>100 μg/cm³). Evaluation through a hen's egg test-chorioallantoic membrane assay confirmed that AE N-PCs were biocompatible, with no irritation induced, promoting safe skin application. Significant PACT potential against <i>Staphylococcus saprophyticus</i> was observed, achieving over 3.8 log reduction in bacterial viability under irradiation with higher effectiveness compared to M-PCs. Thus, the developed PCs incorporated within MNs present a novel, effective strategy for MN-PACT dual targeting of ABSSTIs, addressing challenges in solubility and delivery for hydrophobic PSs while mitigating antimicrobial resistance concerns.