The daily oral administration of acetylcholinesterase (AChE) inhibitors for Alzheimer’s disease features low patient compliance and can lead to low efficacy or high toxicity owing to irregular intake. Herein, we developed a subcutaneously injectable hyaluronic acid hydrogel (MLC/HSA hydrogel) hybridized with microstructured lipid carriers (MLCs) and human serum albumin (HSA) for the sustained release of donepezil (DNP) with reduced initial burst release. The lipid carrier was designed to have a microsized mean diameter (32.6 ± 12.8 µm) to be well-localized in the hydrogel. The hybridization of MLCs and HSA enhanced the structural integrity of the HA hydrogel, as demonstrated by the measurements of storage modulus (G′), loss modulus (G″), and viscosity. In the pharmacokinetic study, subcutaneous administration of MLC/HSA hydrogel in rats prolonged the release of DNP for up to seven days and reduced the initial plasma concentration, where the C_max value was 0.3-fold lower than that of the control hydrogel without a significant change in the AUC_last value. Histological analyses of the hydrogels supported their biocompatibility for subcutaneous injection. These results suggest that a new hybrid MLC/HSA hydrogel could be promising as a subcutaneously injectable controlled drug delivery system for the treatment of Alzheimer’s disease.

Background/Objectives: Semaglutide, a long-acting glucagon-like peptide-1 (GLP-1) analog for type 2 diabetes and obesity, requires sensitive and high-throughput bioanalytical methods to support pharmacokinetic studies. However, previously reported liquid chromatography–tandem mass spectrometry (LC–MS/MS) assays have been limited by lengthy run times (~18 min) and suboptimal sensitivity. This study aimed to develop and validate a rapid, sensitive LC–MS/MS method for quantifying semaglutide in plasma. Methods: Plasma samples (50 μL) were prepared by acetone-mediated protein precipitation followed by solid-phase extraction. Chromatographic separation was performed on a Cadenza CD-C18 MF column within 9 min, using positive electrospray ionization in multiple reaction monitoring mode with the transitions m/z 1029.4 → 110.1 for semaglutide and m/z 938.9 → 109.9 for liraglutide (internal standard). Validation followed the U.S. Food and Drug Administration (FDA) bioanalytical guidelines. Results: The assay showed a lower limit of quantification of 1 ng/mL with linearity across 1–500 ng/mL (R² = 0.9999), with sharp peak shape and no carryover. Intra- and inter-day accuracies were 95.69–103.76% and 94.93–100.08%, with precision ≤4.50% and ≤5.88%. Recovery (93.05–107.95%) and matrix effects (96.34–104.12%) were consistent across quality control levels, and the analyte was stable under all tested conditions. The method was successfully applied to a pharmacokinetic study in Sprague–Dawley rats following subcutaneous administration of 50 μg semaglutide. Conclusions: The validated method offers shorter analysis time, improved sensitivity, and reduced sample volume compared with previously reported assays, supporting its application in preclinical pharmacokinetic studies of semaglutide and related GLP-1 analogs.

Background/Objectives: Androgenetic alopecia (AGA) is the most prevalent form of hair loss. Although topical minoxidil (MNX) is widely used to treat AGA, its efficacy is limited by poor penetration across the stratum corneum. This study evaluated radiofrequency (RF) microporation as a means of enhancing cutaneous MNX delivery and hair-regrowth efficacy in a dihydrotestosterone (DHT)-induced AGA mouse model. Methods: RF-induced skin permeabilization and barrier recovery were assessed in rats using methylene blue and rhodamine B staining. In vivo skin deposition and pharmacokinetic studies were conducted to quantify cutaneous MNX accumulation and systemic exposure. Hair-regrowth efficacy was evaluated in DHT-treated mice. Results: RF microporation generated transient microchannels in the stratum corneum, increased rhodamine B penetration into deeper skin layers, and allowed substantial barrier recovery within 24 h. RF pretreatment significantly increased MNX deposition in the epidermis/dermis by 2.40-fold at 1 h and 1.94-fold at 3 h compared with topical MNX alone. RF-assisted topical administration resulted in a relative bioavailability of 11.17%, compared with 4.74% for topical administration without RF, while dose-normalized systemic exposure remained substantially lower than that following oral administration. In the AGA model, RF-assisted MNX treatment significantly increased hair coverage, length, and shaft thickness. Histological analysis further showed more prominent follicular structures in the RF-assisted MNX groups. Conclusions: RF microporation creates transient microchannels that enhance cutaneous MNX delivery and improve hair-regrowth efficacy. Importantly, RF-assisted topical administration maintained substantially lower systemic exposure than oral administration, supporting its potential as a needle-free strategy for topical AGA therapy and further translational evaluation.

Background/Objectives: Arenicolide A (ArA), a 26-membered macrolide from Micromonospora sp. GR10, is active against Mycobacterium tuberculosis, including multidrug-resistant strains. We developed and validated a liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for ArA in rat plasma and applied it to pharmacokinetic studies. Methods: Plasma (50 µL) was processed by protein precipitation, and analyzed using 4 min isocratic C₁₈ chromatography with positive-ion multiple reaction monitoring (m/z 827.5 → 765.5 for ArA; m/z 237.1 → 194.1 for carbamazepine, internal standard). Validation was performed with reference to the International Council for Harmonisation M10 guideline. Pharmacokinetics were evaluated in male Sprague–Dawley rats after intravenous (1 mg/kg) or oral (5 or 10 mg/kg) administration. Passive permeability, aqueous solubility and rat microsomal depletion were also evaluated. Results: The assay was linear over 2.0–2000 ng/mL (r² > 0.996), with a lower limit of quantification of 2.0 ng/mL. Within- and between-run relative errors were −5.81 to 2.30% and −3.20 to −0.10%, with precision ≤9.01% and ≤10.38%. Extraction recovery was 87.7–96.5%, and matrix effects were consistent across six plasma lots. ArA was stable under pre- and post-preparative conditions. Following intravenous administration, ArA showed a terminal half-life of 0.78 ± 0.08 h and plasma clearance of 26.1 ± 2.5 mL/min/kg. Absolute oral bioavailability was 16.8% and 14.2% at oral doses of 5 and 10 mg/kg, respectively. ArA exhibited high passive permeability, limited aqueous solubility of approximately 0.1 mg/mL, and slow microsomal depletion. Conclusions: This validated method enabled characterization of ArA pharmacokinetics and oral bioavailability. This method supports a reliable analytical platform for further formulation and preclinical evaluation of ArA as an anti-tuberculosis lead.