AAPS PharmSciTech最新文献

Psoriasis is a chronic, immune-mediated inflammatory skin disorder characterized by keratinocyte hyperproliferation, dysregulated immune signaling and systemic comorbidities, affecting nearly 2–3% of the global population. Although conventional therapies have improved disease management, they remain limited by poor drug penetration, systemic toxicity, adverse effects, high costs and relapse after discontinuation. The distinctive pathophysiology of psoriatic skin, with its thickened stratum corneum and aberrant immune microenvironment, poses persistent challenges to achieving targeted, sustained drug delivery. To address these limitations, emerging drug delivery systems and devices are being engineered to optimize therapeutic outcomes. Nanocarrier-based platforms are enabling enhanced drug localization, improved bioavailability and modulation of key inflammatory pathways. In parallel, microneedle-assisted delivery, hydrogel scaffolds and nanofiber matrices are establishing themselves as versatile technologies for localized, sustained and patient-friendly administration. Furthermore, stimuli-responsive and bio-inspired systems, incorporating plant-derived bioactives or extracellular vesicles, are advancing the paradigm of personalized and precision medicine in dermatology. This review critically evaluates recent progress in advanced therapeutics, nanotechnology-driven platforms and bioengineered systems for psoriasis therapy, with emphasis on their mechanisms, drug targeting, translational potential and future integration into clinical practice. Additionally, this review provides insight into how advanced delivery systems may redefine the future landscape of psoriasis management.

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The strong hygroscopicity of herbal extracts poses significant challenges for their formulation into stable solid dosage forms. In this study, Wang Bi (WB) extract pellets with enhanced moisture resistance were developed using asymmetric liquid layering (ALL) technology combined with mesoporous silica (MS) and magnesium stearate (Mg-st). This approach effectively isolates the pellets from ambient moisture, thereby improving their resistance to water vapor. Pellets containing 89.18% WB extracts were comprehensively characterized. Surface-modified pellets (SMs) prepared via ALL exhibited notable differences in texture, size, and sphericity compared with commercial pellets (CMs) produced by rotary granulation and polymer film coating. Hygroscopicity was evaluated by measuring weight changes under high relative humidity conditions. These morphological changes resulted in significant performance enhancement, with the hygroscopicity reduced to 1.94% after 10 days at 75% relative humidity, corresponding to approximately 25% of that measured for CMs. Moreover, the preparation process and excipients employed did not affect the release profile of the WB extracts. Collectively, these findings demonstrate that the combination of ALL technology with MS and Mg-st represents an effective strategy to enhance moisture resistance, offering a novel means to improve the stability and quality of traditional Chinese medicine formulations.

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High flow therapy (HFT) delivers heated and humidified gas at flow rates up to 60 L/min to hypoxemic subjects, but is not conducive to simultaneous administration of pharmaceutical aerosols. Aerosol losses occur due to circuit wall impaction, environmental loss and particle growth from high humidity; resulting in poor lung delivery efficiency. This study compares two strategies for delivering dry powder aerosols during 60 L/min humidified HFT: a circuit connector (HFT-CC) which integrates directly into the standard HFT flow pathway, and an interface connector (HFT-IC) designed to bypass delivery line losses by directly injecting aerosol into the nasal prongs. Experiments were conducted using an anatomically-realistic in vitro adult nasal airway model with physiological breathing patterns, albuterol sulfate excipient enhanced growth (AS-EEG) dry powder formulation, air-jet aerosolization engine, and custom air actuation system. The HFT-CC approach improved lung delivery to 25.6% compared to existing published data (12.8%) but was limited by losses in the circuit tubing and nasal interface. The HFT-IC approach with a split nasal interface achieved 45.1% lung delivery (HFT-IC3), nearly a fourfold improvement from previously published results, by isolating aerosol flow from HFT flow and eliminating upstream losses. While nose-throat (NT) deposition in HFT-IC3 remained high (39.6%), this approach presents an attractive target for future computational and experimental optimization. These findings prove that efficient dry powder aerosol lung delivery during 60 L/min humidified HFT is achievable, laying the groundwork for translational advances in the efficient delivery of pulmonary therapies such as surfactants, antibiotics, anti-inflammatories, and antivirals during ventilatory support.

Clinical in-use study of monoclonal antibody (mAb) drug products is a critical component of product development, designed to assess the stability and compatibility of mAbs with clinical diluents and delivery materials. These studies often involve diluting mAbs into 5% dextrose (D5W), a common intravenous diluent that can pose analytical challenges. When D5W IV bags are subjected to terminal steam sterilization, the dextrose undergoes degradation into glucose degradation products (GDPs), including 5-hydroxymethylfurfural (5-HMF), which absorbs strongly at 284 nm and can interfere with UV absorbance-based protein quantification at 280 nm (A280). Although GDP formation in D5W IV bags is well documented, its impact on A280-based protein quantification, especially at low concentrations, has not been previously reported. In this study, we investigated the influence of GDPs on protein quantification in D5W-diluted samples, with a focus on mAb concentrations ≤ 1.0 mg/mL. We also evaluated the effects of temperature and storage duration on GDP accumulation. Our findings revealed that GDP levels varied across IV bags and increased with prolonged storage at elevated temperatures. Using a model mAb, we demonstrated that D5W interferes with A280-based protein measurements. While baseline correction using D5W from the same IV bag reduced interference, variability persisted when using D5W from different bags, even within the same lot. To address this challenge, we implemented a Protein-A-based affinity chromatography method that enabled accurate quantification of mAb concentrations in the range 0.01–1.0 mg/mL using a UV detector and 0.005–1.0 mg/mL using a fluorescence detector. These findings highlight that D5W can introduce significant discrepancies in A280-based protein measurements and demonstrate that Protein-A affinity chromatography provides a reliable alternative for quantifying mAbs in D5W-diluted samples by effectively mitigating GDP interference.

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The stratum corneum represents the main barrier to transdermal drug delivery, particularly for hydrophilic and ionized compounds such as aminophylline. In this study, the solubility–permeability–matrix interplay was investigated using aminophylline and theophylline as model drugs in various matrix-type transdermal patches based on either hydroxypropyl methylcellulose (HPMC) or silicone-based Bio-PSA (Biomedical Pressure-Sensitive Adhesive). Franz diffusion cells with porcine ear skin were used to evaluate in vitro skin permeation, and complementary release studies were conducted using dialysis membranes. Aminophylline exhibited significantly higher transdermal flux than theophylline in both matrix systems, despite its increased hydrophilicity and ionization. This effect is attributed to its capacity to maintain high thermodynamic activity when formulated as a suspension, thereby intensifying chemical potential gradients and supporting aqueous pathway permeation. Penetration enhancers showed distinct mechanisms of action. Geraniol, a lipophilic terpene alcohol, significantly increased skin permeation by disrupting stratum corneum lipid lamellae and facilitating transient hydrophilic channels. In contrast, Transcutol P acted primarily by increasing drug solubility within the matrix and forming a reservoir in the stratum corneum. However, its enhancing effect remained modest due to limited interaction with the barrier and slow release from the silicone matrix. These findings highlight the critical role of drug solubility and enhancer molecular properties in the transdermal delivery of hydrophilic drugs. In addition, matrix parameters like thickness, hydration and release properties need to be properly engineered for making optimal use of the involved solubility-permeability interplay.

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Cannabinoids such as cannabidiol (CBD) and tetrahydrocannabinol (THC) have garnered significant interest for their broad-spectrum pharmacological activity in managing chronic pain, neurological disorders, and cancer-associated symptoms. Despite their therapeutic promise, clinical translation remains hindered by poor aqueous solubility, extensive first-pass metabolism, and inconsistent systemic exposure following oral administration. Oral mucosal drug delivery systems offer a viable alternative by enabling transmucosal absorption, bypassing hepatic metabolism, and facilitating both rapid and sustained drug release. This review examines the evolution and design of oral mucosal dosage forms, including fast-dissolving films, mucoadhesive matrices, in situ gels, and particulate systems and highlights the critical role of formulation strategies in enhancing cannabinoid bioavailability. Fabrication techniques such as solvent casting, hot melt extrusion, and emerging 3D printing methods are also discussed, with a focus on their potential to enable personalized dosage forms. Furthermore, the integration of permeation enhancers like terpenes, and novel systems such as inclusion complexes and lipid-based carriers, presents new opportunities for improving the solubility and stability of lipophilic cannabinoids. Together, these innovations provide a framework for the development of stable, effective, and patient-centric oral mucosal cannabinoid delivery platforms with improved pharmacokinetic and therapeutic profiles.

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Multiple sclerosis is a neuroinflammatory disease characterized by demyelination and progressive neurological decline. Teriflunomide, a first-line immunomodulatory agent, faces limitations due to oral route of administration and systemic toxicity. To overcome these challenges, we developed a nose-to-brain delivery system comprising teriflunomide-loaded ginger-derived extracellular vesicles (G-EVs) embedded in an in situ nasal gel. G-EVs were isolated via serial centrifugation and double filtration and characterized for particle size (103.5 ± 1.09 nm) and zeta potential (-17.3 ± 0.32 mV) confirming nanoscale uniformity. Teriflunomide was loaded into G-EVs with an entrapment efficiency of 63.24 ± 0.75%. In vitro release studies revealed a biphasic drug release profile; an initial burst release of 3% in 24 h followed by sustained release over 21 days. The cytotoxicity of the G-EVs, loaded G-EVs and the drug was found to be non-toxic at lower concentrations (< 0.5 mg/ml). It was observed that drug loading enhanced cellular internalization of the G-EVs. Pluronic F127 and chitosan was used to formulate a thermoresponsive and mucoadhesive nasal gel. Rheological analysis demonstrated a sol–gel transition at 34.13 ± 0.76 °C, with high G′ values indicating more elasticity and stiffness, behaving more like a solid. Mucoadhesion testing confirmed strong retention on mucin through texture analysis and in vitro studies. The loaded G-EVs were added to the nasal gel and SEM was performed to confirm uniformity. This formulation could offer a synergistic platform for brain drug delivery, combining the biocompatibility of naturally-derived EVs with the thermoresponsive nasal gel.

Glaucoma, a leading cause of irreversible blindness, is driven by elevated intraocular pressure (IOP) and oxidative retinal damage. Resveratrol (RES), a polyphenolic antioxidant with neuroprotective activity, offers therapeutic potential but suffers from poor aqueous solubility and low ocular bioavailability. This study developed and evaluated a cationic phyto-microemulsion to enhance ocular delivery of RES. RES-loaded phyto-microemulsion (RES-ME) were formulated using isopropyl myristate, Tween 80, and propylene glycol, with stearylamine (SA) imparting positive surface charge. Optimized uncoated phyto-microemulsion (RTPG) and SA-coated phyto-microemulsion (SRTPG) were characterized for physicochemical properties, mucoadhesive strength, in vitro drug release, ex vivo goat corneal permeation, antioxidant activity, ocular irritation, and IOP-lowering efficacy in a dexamethasone-induced rat glaucoma model. SRTPG exhibited a globule size of 186.2 ± 6.24 nm, PDI 0.147 ± 0.04, and zeta potential + 28 ± 4.56 mV. Drug release was sustained (70–75% over 8 h) and best fitted the Higuchi model (R2 > 0.98). SRTPG achieved markedly higher corneal permeation (750.3 µg/cm2) versus RTPG. HET-CAM and histology confirmed minimal irritancy and preserved corneal architecture. In vivo, SRTPG produced a maximal IOP reduction of 23.88% at 4 h and prolonged efficacy (AUC₀–₈_h = 114.28), comparable to dorzolamide. The enhanced performance is attributed to cationic surface charge–mediated mucoadhesion and lipidic microemulsion–facilitated transcorneal transport. SRTPG offer safe, sustained, and penetration-enhanced ocular delivery, with dual IOP-lowering and antioxidant effects, representing a promising nanocarrier platform for glaucoma management.

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Amiodarone hydrochloride (AMH) is a potent anti-arrhythmic drug used for the treatment of ventricular tachycardia and ventricular fibrillation, but its clinical utility is limited by low aqueous solubility (~ 0.2 mg/mL) and poor dissolution. Co-crystallisation offers a promising strategy to improve the solubility and bioavailability of Biopharmaceutics Classification System Class II drugs. This study focused on developing an immediate-release tablet containing AMH co-crystals with enhanced solubility and dissolution characteristics. Co-former selection was guided by excess enthalpy and Hansen solubility parameter calculations, leading to the synthesis of two co-crystals, amiodarone–tartaric acid and amiodarone–phthalic acid, via liquid-assisted grinding. Characterisation was performed using powder X-ray diffraction, differential scanning calorimetry, Fourier transform infrared spectroscopy and scanning electron microscopy. The amiodarone–tartaric acid co-crystal exhibited superior solubility (0.891 mg/mL and 0.583 mg/mL in acetate buffer and water, respectively) compared with the pure drug. Polymer screening identified polyethylene glycol 4000 as optimal for controlling solution-mediated phase transformation. The tablet formulation, optimised using a Design of Experiments approach, achieved more than 90% drug release in 20 min compared with 95% in 120 min for a marketed product. Stability studies confirmed retention of crystallinity, solubility, and assay after six months, demonstrating the formulation’s robustness and potential clinical applicability.

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