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The aim of the study is to formulate an injectable nanocrystalline suspension (NS) of dutasteride (DTS), a hydrophobic 5α-reductase inhibitor used to treat benign prostatic hyperplasia and scalp hair loss, for parenteral long-acting delivery. A DTS-loaded NS (DTS-NS, 40 mg/mL DTS) was prepared using a lab-scale bead-milling technique. The optimized DTS-NS prepared using Tween 80 (0.5% w/v) as a nano-suspending agent, was characterized as follows: rod/rectangular shape; particle size of 324 nm; zeta potential of −11 mV; and decreased drug crystallinity compared with intact drug powder. The DTS-NS exhibited a markedly protracted drug concentration-time profile following intramuscular injection, reaching a maximum concentration after 8.40 days, with an elimination half-life of 9.94 days in rats. Histopathological observations revealed a granulomatous inflammatory response at the injection site 7 days after intramuscular administration, which significantly subsided by day 14 and showed minimal inflammation by day 28. These findings suggest that the nanosuspension system is a promising approach for the sustained release parenteral DTS delivery, with a protracted pharmacokinetic profile and tolerable local inflammation.

Donepezil (DPZ), a piperidine-based reversible cholinesterase inhibitor, finds extensive use in treating Alzheimer's disease (AD). Originally designed as an oral formulation, DPZ encounters drawbacks such as a brief duration of action and reduced treatment effectiveness in elderly patients with memory impairment or difficulty swallowing medications. To address these issues and improve patient compliance, researchers are actively exploring alternative DPZ formulations. Consequently, reliable methods are necessary to quantitate DPZ in biological samples for in vivo assessment. Therefore, we propose an efficient, sensitive, wide-dynamic, and cost-effective method for quantitating DPZ in rat plasma. Our method employs liquid-liquid extraction (LLE) followed by liquid chromatography and tandem mass spectrometry, enabling in vivo evaluation of novel DPZ formulations. Notably, our method requires only 20 μL of rat plasma and employs icopezil as the internal standard-a cost-effective compound with chemical similarity to DPZ. We meticulously optimized LLE conditions, taking into account factor interactions through design of experiments (DOE). Our rapid and straightforward extraction and purification involved using 500 μL of pure methyl tert-butyl ether to extract DPZ from the sample within five minutes. The dynamic range of the method extends from 0.5 ng/mL to 1,000 ng/mL, demonstrating excellent sensitivity and suitability for pharmacokinetic studies across diverse DPZ formulations. Following the FDA guidelines, we rigorously validated the developed method, evaluating selectivity, linearity (with a coefficient of determination ≥0.9999), accuracy (ranging from 96.0% to 109.6%), precision (≤13.9%), matrix effect (92.2% to 103.8%), recovery (98.5% to 106.8%), the lower limit of quantitation (0.5 ng/mL), and stability. Finally, we effectively employed the validated method for the long-term pharmacokinetic assessment of a DPZ formulation. We expect that this approach will make a substantial contribution to the advancement of new DPZ formulations, ultimately benefiting individuals afflicted by AD.

The mammary gland is a heterogeneous organ comprising of immune cells, surrounding adipose stromal cells, vascular cells, mammary epithelial, and cancer stem cells. In response to nutritional stimuli, dynamic interactions amongst these cell populations can be modulated, consequently leading to an alteration of the glandular function, physiology, and ultimately disease pathogenesis. For example, obesity, a chronic over-nutritional condition, is known to disrupt homeostasis within the mammary gland and increase risk of breast cancer development. In contrast, emerging evidence has demonstrated that fasting or caloric restriction can negatively impact mammary tumorigenesis. However, how fasting induces phenotypic and functional population differences in the mammary microenvironment is not well understood. In this review, we will provide a detailed overview on the effect of nutritional conditions (i.e., overnutrition or fasting) on the mammary gland microenvironment and its impact on mammary tumor progression.