Advancements in drug delivery systems (DDSs) have developed pharmacotherapy by enabling precise control over drug pharmacokinetics (PKs), enhancing therapeutic efficacy, minimizing toxicity, and improving patient compliance. This review comprehensively examines emerging DDS strategies designed to optimize absorption, distribution, metabolism, and excretion (ADME) of therapeutic agents. Key innovations include nanotechnology-based carriers (liposomes, polymeric nanoparticles, and dendrimers), stimuli-responsive and smart delivery systems, site-specific and tissue-targeted DDS, and prodrug DDS hybrid approaches. Integration of PK modeling, artificial intelligence (AI), and omics data has facilitated personalized and patient-specific therapy, while advanced computational tools allow predictive simulation of drug behavior. Translational challenges such as scale-up, regulatory approval, interpatient variability, long-term safety, and clinical trial design are discussed, alongside strategies to overcome these barriers. Future perspectives emphasize AI-assisted optimization, multimodal DDS combining therapeutic and diagnostic functionalities, biodegradable and sustainable materials, and regenerative and cellular delivery platforms. Collectively, these developments highlight a paradigm shift toward adaptive, precise, and personalized pharmacotherapy, bridging preclinical innovation with clinical application. This review provides a comprehensive framework for understanding the current landscape and future directions of DDS in controlling PKs, ultimately supporting safer and more effective patient-centric therapies.
Polycystic ovary syndrome (PCOS) is a prevalent and complex hormone-metabolic condition that impacts females of reproductive age. Current pharmacological treatments often address limited symptoms, may involve long-term use of synthetic drugs, and are frequently associated with adverse effects and limited patient adherence. In recent years, natural therapeutic agents such as Lutein and Myo-inositol have acquired increasing interest due to their promising biological properties and minimal side effects. Strong antioxidant lutein aids in lowering inflammation and oxidative stress, while Myo-inositol, a naturally occurring sugar alcohol, has insulin-sensitizing and ovulation-inducing effects, making them ideal candidates for addressing the multifaceted pathophysiology of PCOS. Nevertheless, the application of these compounds in therapy is restricted by their limited solubility, reduced bioavailability, and brief half-life. To overcome these challenges, the present research focused on the development and assessment of sustained-release poly-herbal microspheres incorporating Lutein and Myo-inositol using the emulsification method. Nine different formulations (F1 to F9) were prepared and characterized for in vitro parameters. Among the nine formulations developed, one optimized formulation demonstrated high encapsulation efficiency (>90%), satisfactory production yield (>85%), and sustained drug release of approximately 90% over 8 h. In the letrozole-induced PCOS rat model, treatment significantly reduced malondialdehyde (MDA) levels and increased glutathione (GSH) levels compared with the disease control group (p < 0.001). Histopathological evaluation showed a marked reduction in cystic follicles and restoration of normal ovarian morphology in the treated group. Furthermore, in vivo efficacy was confirmed through histopathological examination of ovarian tissues in animal models, where treated groups, especially T3, receiving the highest concentration demonstrated restoration of normal ovarian architecture, reduction in cystic follicles, and improved follicular development. These outcomes support the hypothesis that a combination of Lutein and Myo-inositol, when delivered through a sustained-release microsphere system, can effectively target oxidative stress, insulin resistance, hormonal imbalance, and ovarian dysfunction, which are central to PCOS pathogenesis.
This study presents the novel quality by design (QbD)-assisted RP-HPLC method for the simultaneous estimation of relatlimab and nivolumab in both bulk and pharmaceutical formulations, utilizing a statistically optimized design via central composite design (CCD). Optimization was performed by CCD by selecting mobile phase ratio of acetonitrile, pH of buffer, and flow rate as factors and evaluating responses, namely retention time and tailing factor, through Waters Alliance-e2695, which occurred using a Kromasil C18 (150 × 4.6 mm, 3.5 µm) column that operated with a mobile phase composed of acetonitrile:ammonium acetate in the ratio of 20:80 v/v. The detector used a photodiode array for absorbance-based reading at 236 nm with an ambient temperature setup. The detection system worked at 1.0 mL/min flow rates. The results obtained from the validation parameters demonstrate that this RP-HPLC method, developed using the QbD approach, is robust and dependable. ICH guidelines served as the basis for conducting the validation of this proposed method. Forced degradation is carried out at various stress conditions. The method offers a rapid, robust, and cost-effective analytical solution with high precision and accuracy, validated as per ICH guidelines, and is well-suited for routine quality control and stability studies.
Diabetic peripheral neuropathy (DPN) is a common chronic complication of diabetes that severely impairs quality of life. The Yi-Qi-Bu-Shen Recipe (YQBS) alleviates diabetic complications, but its mechanism against DPN remains unclear. This study aimed to explore the underlying mechanism of YQBS against DPN using network pharmacology and to verify its effects on peripheral nerve injury and modulation of the AGE-RAGE/NF-κB signaling pathway in vivo . Active components of YQBS were computationally screened via the TCMSP database, potential targets were predicted using GeneCards and OMIM, and key pathways were analyzed by KEGG enrichment. Molecular docking was performed to assess binding affinities. In animal experiments, streptozotocin-induced DPN rats were randomized into control, model, low-dose YQBS, and high-dose YQBS groups. After 12 weeks, nerve conduction velocity, sciatic nerve pathology, nerve repair–related proteins, and RAGE/NF-κB p65 phosphorylation were evaluated. Network pharmacology predicted quercetin, β-sitosterol, and formononetin as major active components, PTGS2 and NOS2 as core targets, and AGE-RAGE/PI3K–Akt as key pathways. Molecular docking predicted favorable binding affinities. Animal experiments confirmed that YQBS significantly improved nerve conduction, alleviated nerve damage, upregulated repair proteins, and inhibited RAGE expression and NF-κB p65 phosphorylation. In conclusion, YQBS ameliorates DPN in rats, with suppression of AGE-RAGE/NF-κB pathway activation.
Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus. Circadian rhythm disorders are related to the pathogenesis of LN. This study aims to identify the core circadian rhythm–related genes in LN and identify the potential natural active compounds for LN treatment. In the present study, cyclin A2 (CCNA2) and cyclin-dependent kinase inhibitor 3 (CDKN3) were identified as the core targets most related to the circadian rhythm of LN. Both of them were upregulated in blood and kidney tissue samples in LN and had high diagnostic efficacy. Deguelin had strong binding capabilities with CCNA2 and CDKN3 proteins. Deguelin could dose-dependently alleviate lipopolysaccharide-induced human kidney-2 (HK-2) cell damage, inhibit cell apoptosis and the release of inflammatory factors, downregulate the mRNA and protein expression levels of core genes CCNA2 and CDKN3, and inhibit the activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. The protective effect of deguelin could be reversed by AKT activator SC79 treatment. In summary, CCNA2 and CDKN3 are core genes related to the circadian rhythm in LN. Deguelin probably alleviates renal tubular epithelial cell injury by modulating the expression levels of core genes CCNA2 and CDKN3, inhibiting the activation of the PI3K/Akt signaling pathway, and thus has the potential to become a therapeutic agent for LN.
