AAPS PharmSciTech最新文献

Hesperidin, a flavanone, exhibits antioxidant, anti-inflammatory, and anti-amyloidogenic properties, making it a promising candidate for the treatment of Alzheimer's disease. The hesperidin possesses poor solubility, and its oral bioavailability is < 20%. Therefore, hesperidin cochleates (HC) were prepared using the trapping method of calcium ions into preformed liposomes to improve oral bioavailability. The HC formulation was statistically optimized by applying a 3-level factorial design. Optimum cochleates were observed, with an average particle size of 398.9 nm, a zeta potential of -39.1 mV, and an entrapment efficiency of 92.2%, respectively. The in vitro release of hesperidin from cochleates (Batch 15) was 97% in phosphate buffer at pH 7.4 after 24 h. The HC formulation exhibited a 1% release at a gastric pH of 1.2, indicating its stability in the stomach, allowing the formulation to reach the absorption site. In Wistar rats, a comparative pharmacokinetic study was conducted between hesperidin liposomes and HC. Hesperidin concentration was 2.21-fold higher in plasma and 1.2-fold higher in the brain after cochleates administration than in the liposomal formulation and more than 25-fold greater than plain API. Thus, cochleates may be superior oral carriers for hesperidin, improving its oral bioavailability for the treatment of Alzheimer's disease.

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Chemotherapy resistance continues to represent a profound impediment in oncologic therapy, and the co-delivery of chemotherapeutic agents with distinct mechanisms of action offers an effective approach. In the present investigation, we developed Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) loaded with Sorafenib (SOR), a ferroptosis inducer, and Venetoclax (VTX), an apoptosis inducer for combined cell death. These PLGA(SOR + VTX) NPs were formulated via nanoprecipitation followed by successive coating with polydopamine (PDA) and bovine serum albumin (BSA). PDA was utilized to facilitate BSA linkage while BSA enabled targeting of albondin and secreted protein acidic and rich in cysteine (SPARC) receptors. BSA-PDA-PLGA(SOR + VTX) NPs revealed a spherical morphology with a size of 183.6 ± 6.20 nm, a PDI of 0.108 ± 0.02, and a Z-potential of -23.3 ± 1.03 mV with SOR and VTX ratiometrically (1:1) loaded into the nanoparticles. The nanoparticles exhibited sustained release behaviour and were assessed to be hemocompatible. The cell uptake studies reflected better cytoplasmic internalization, and the formulation resulted in a reduction in the IC₅₀ value by 2.74, 3.40, and 2.90-fold compared to the physical combination of SOR + VTX in MDA-MB-231, A549, and HeLa cell lines, respectively. The apoptosis index of the formulation was 1.42, 1.40 and 1.40-fold higher than that of SOR + VTX in MDA-MB-231, A549 and HeLa, respectively. Moreover, BSA-PDA-PLGA(SOR + VTX) NPs induced a greater generation of reactive oxygen species and mitochondrial membrane potential depolarization. They also demonstrated escalated ferroptosis by depleting glutathione and elevating malondialdehyde levels across all cell lines. Thus, co-delivery of SOR and VTX via BSA-PDA-PLGA NP exhibited synergistic activity in targeting different tumor cells.

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Physiologically based pharmacokinetic (PBPK) modelling can be utilized in dermal drug development and to support regulatory assessments by integrating information related to the active pharmaceutical ingredient (API), drug product, and skin physiology into a mechanistic simulation framework. The purpose of this study was to develop a mechanistic skin absorption model to predict the absorption of lidocaine and prilocaine following topical application of EMLA cream (lidocaine/prilocaine topical cream, 2.5%/2.5%) in virtual subjects. The multi-phase multi-layer mechanistic dermal absorption (MPML MechDermA™) model was used to simulate in vitro permeation of both APIs. Changes in formulation pH post application were studied experimentally, and these dynamic changes were captured in the model when simulating finite dose studies using ex vivo human skin. A dermal in vivo PBPK model for the EMLA cream (lidocaine/prilocaine topical cream, 2.5%/2.5%) was developed and validated. The model was able to consider the formulation and trial design differences of in vivo studies and adequately simulated the observed data. Further model validation was performed against a manufactured cream with microstructural characteristics that were different compared to the EMLA cream. Through virtual bioequivalence assessments, the in vivo model demonstrated that it may be used to predict the impact of differences in drug product quality attributes on the in vivo performance of a topically applied drug product and inform decisions related to product development.

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Background

Artificial intelligence is emerging as a transformative force in pharmaceutical sciences by enabling data-driven decision-making, automation, and predictive modeling. In ocular drug delivery, where therapeutic efficacy is hindered by complex anatomical and physiological barriers, AI presents significant opportunities to overcome these challenges. Its ability to optimize drug combinations, design smart delivery systems, and personalize therapies underscores its relevance in advancing ophthalmic care.

Area Covered

This review explores the intersection of AI and ophthalmic therapeutics, highlighting its role in formulation design, disease prediction, patient-specific treatment strategies, and smart delivery platforms, and outlines future research directions to bridge current gaps. Machine learning is advancing ocular drug delivery by optimizing nano-formulations, predicting release kinetics, and modeling pharmacokinetics. Alongside AI-powered diagnostics and integration with biosensors, contact lenses, and implants, these innovations are driving real-time monitoring and truly personalized ocular therapy and early detection and monitoring ocular diseases such as glaucoma, diabetic retinopathy, and macular degeneration. Challenges including limited clinical validation, model interpretability, data security, and regulatory complexities are highlighted. Furthermore, current gaps such as the lack of comprehensive studies on AI-assisted stimuli-responsive carriers and integration with patient-specific data are identified. Future directions emphasize explainable AI, smart biomaterials, and robust ethical-regulatory frameworks for clinical translation.

Expert Opinion

AI integration in ocular therapeutics marks a paradigm shift toward precision drug delivery and personalized care. Despite progress, challenges in explainability, regulation, and validation remain, yet innovations in AI-driven nanocarriers, smart systems, and real-time monitoring hold the potential to revolutionize ocular pharmacology overcoming limitations of conventional therapies.

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Olmesartan Medoxomil (OLM) is a prodrug of an angiotensin II receptor antagonist and a P-glycoprotein (P-gp) substrate that is converted into Olmesartan by esterases, resulting in low oral bioavailability (26%). The aim of the present study was to formulate Olmesartan Medoxomil liposomes by thin film hydration method using Vitamin E TPGS (P gp inhibitor). Initial screening of excipients was conducted using the One Factor At A Time (OFAT) approach, while optimization was performed using Box-Behnken Design (BBD). The drug-to-lipid ratio, the amount of cholesterol, and the surfactant were identified as independent variables, with vesicle size (nm) and entrapment efficiency (%) as dependent variables. Key process parameters were evaluated through OFAT analysis, and the formulation was optimized using BBD. The prepared liposomes were characterized through vesicle size (nm), zeta potential (mV), drug loading (%), Transmission Electron Microscopy (TEM), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR), and Gas Chromatography (GC), followed by in vitro dissolution and in vivo pharmacokinetic study in 12 wistar rats. The vesicle size and entrapment efficiency of the optimized formulation were found to be 112.1 nm and 98.88% respectively. In vitro drug release studies were conducted in the USP-II apparatus exhibited a biphasic release pattern compared to the marketed formulation Olmezest®10. In vivo pharmacokinetic studies in wistar rats showed a significant increase in oral bioavailability (3.23 times) of the liposomal formulation of Olmesartan Medoxomil (OLM-LIPO) in comparison to the marketed formulation Olmezest®10.

To improve the functional properties and drying aid role in spray drying of soybean peptide (SP), SP was respectively conjugated with eight saccharides (maltose, lactose, maltodextrin, inulin, α-cyclodextrin (α-CD), β-CD, dextran-20000, and dextran-40000) via wet-heated Maillard reaction, and the efficacy of conjugates in spray-drying of Lycium barbarum extracts rich in low-molecular-weight sugars and organic acids was systematically evaluated. Among the conjugates, SP-α-CD exhibited the highest graft-browning equilibrium index (143.52%) and emulsifying activity index (4.63 m²/g). Through Box-Behnken experimental optimization, the ideal conjugation conditions were identified as: 30 mg/mL SP concentration, 70 °C reaction temperature, and 2.5 h reaction time. When SP-α-CD (10% w/w) co-spray dried with the extract (90%), it could effectively prevent the wall sticking, and the powder yield reached 73.94% (~ 20.74% higher than that achieved by the native SP). The hygroscopicity and softening point (being increased to 69.77 °C) of the powder was improved. X-Ray photoelectron spectroscopy analysis revealed that during spray drying, SP-α-CD tends to distribute on the powder surface, encapsulating the extract components and achieving stronger drying aid and encapsulation effects. Collectively, it is expected to be developed as a spray drying aid for sugar-containing extracts and as a wall material for food and pharmaceutical microencapsulation.

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Electrospray technology is a process capable of forming monodisperse drug nano/microparticles with enhanced solubility or sustained-release effects. This study aimed to fabricate a sustained-release drug delivery system containing trazodone hydrochloride (TZN-SRDDS) by combining electrospray technology with functional carriers (Soluplus®, Carbopol 940, HPMC K4M, and Lecithin) for solubility improving, drug release prolonging and bioavailability enhancing. The optimized TZN-SRDDS exhibited a spherical morphology, with a particle size of (3.456 ± 0.448) μm, a polydispersity index (PDI) of (0.456 ± 0.024), and a zeta potential of (-17.291 ± 2.351) mV. This system showed a high encapsulation efficiency (97.12 ± 1.82%) and maintained good stability for up to 30 days. In vitro release studies indicated that TZN-SRDDS followed first-order kinetics in pH 1.2 hydrochloric acid solution and the Higuchi model in pH 6.8 phosphate-buffered saline (PBS), with the cumulative release rate increased to (80.81 ± 4.26%); both release profiles exhibited a certain sustained-release effect. Cytotoxicity assays confirmed that TZN-SRDDS was non-toxic at concentrations below 2.6 mg/mL, and the formulation showed a relatively sustained cellular uptake effect. Pharmacokinetic studies in rats showed that the time to reach peak concentration (T_max) of TZN-SRDDS was extended from 0.25 h to 1 h, its half-life (t_1/2) was increased from (1.15 ± 0.17) h to (6.71 ± 0.39) h, resulting in a relative bioavailability of 374.64%. This study achieved the synergistic goals of drug solubilization, sustained-release delivery, and enhanced bioavailability. It provides new technical references for the development of pH-sensitive drug formulations using electrospray technology and also expands the research on the development of sustained-release formulations of trazodone hydrochloride.

Cabazitaxel (CTX) is primarily used in the clinical treatment of prostate cancer. The clinical CTX injection (Jevtana®) contains the solubilizer Tween 80, which can lead to serious toxic side effects during intravenous injection. This study developed a novel nanodelivery system for encapsulating CTX, eliminating the need for Tween 80 and addressing current clinical challenges associated with CTX use. The nanodelivery system uses the hydrophilic polymer polyvinylpyrrolidone K12 (PVP K12) as a dispersing agent and a small amount of highly biocompatible sodium cholesteryl sulfate (SCS) as a stabilizer, forming a cabazitaxel nanodispersion (CTX-NP) through the water dispersion method. The CTX-NP exhibited a spherical shape, uniform distribution, a particle size of 128.90 ± 0.42 nm, a PDI of 0.14 ± 0.01, a zeta potential of -65.88 ± 1.23 mV, and a drug encapsulation efficiency of 97.58 ± 0.58%. Furthermore, hemolysis, vascular irritation, and maximum tolerated dose (MTD) experiments indicated that CTX-NP has good biocompatibility compared to cabazitaxel-Tween injection (CTX-TW). The pharmacokinetic studies in rats revealed that, compared to CTX-TW, CTX-NP had an extended half-life (T_1/2), mean residence time (MRT), and a larger area under the drug concentration–time curve (AUC). In the RM-1 prostate cancer mouse model, compared with CTX-TW, the high-dose CTX-NP group showed better tumor inhibition with an inhibition rate of 79.48%, indicating that CTX-NP could achieve superior anti-tumor effects by increasing the administered dose.

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Developing well-tolerated pharmaceutical formulations remains a major challenge in drug delivery. Polysaccharide-based biopolymers, such as chitosan and pectin, provide a renewable and biocompatible platform for modified drug release. Despite its efficacy in Chagas disease, benznidazole (BNZ) is associated with a significant rate of side effects, which often compromise patient adherence. In this study, interpolyelectrolyte complex (IPEC) microparticles loaded with BNZ, using a melt extrusion technique without solvents, were designed and developed to provide therapeutic alternatives for Chagas disease treatment. The incorporation of polyethylene glycol facilitated polymer processing, enabling high-yield microparticle production without organic solvents. The crystalline nature of BNZ was reduced, leading to a more homogeneous distribution within the microparticles, which exhibited excellent flow properties and were suitable for hard gelatin capsule formulation. The system enhanced BNZ solubility in simulated gastric fluid, improved fluid uptake, and demonstrated mucoadhesive properties. Moreover, it provided a delayed BNZ dissolution, independent of dissolution media. Notably, the IPEC-based formulation improved the antiparasitic activity of BNZ against Trypanosoma cruzi while reducing its cytotoxic effects on human endothelial cells. This scalable, biocompatible platform offers a promising strategy for optimizing Chagas disease treatment by potentially minimizing side effects and improving overall therapeutic outcomes.

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Diabetes mellitus (DM) is a clinical syndrome characterized by disturbance in carbohydrate, fat and protein metabolism due to either insulin deficiency or insulin resistance. Oral medications and insulin injections have typically been the conventional delivery modalities of diabetes treatment for both type 1 and patients with advanced type 2 diabetes. In spite of this, these treatments have some drawbacks, including low efficacy, unwanted side effects and the possibility of hypoglycemia. New developments in medication delivery techniques, such as insulin pumps, inhalers and patches, have been made with the intention of enhancing the efficacy of the treatment. Insulin pumps allow for precise and flexible administration of insulin, which, in turn, reduces the number of episodes of low blood sugar. The use of inhalers provides a non-invasive alternative that facilitates rapid glycemic management and increases patient satisfaction. Currently in the process of being developed, insulin patches provide a means of administering insulin that is both simple and painless. In this review, we investigate the efficacy, safety and practicability of various technological breakthroughs, such as insulin pumps, smart insulin pens and continuous glucose monitoring systems. In addition to this, it addresses the challenges that are preventing a wider acceptance, such as the costs, the availability and the requirements for training. In order to enhance patient outcomes and usher in a new era of diabetes care that is increasingly driven by technology, the report places a strong emphasis on the necessity of continued research and innovation.

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