AAPS PharmSciTech最新文献_第4页

Smart Stings of Nature: Harnessing Microneedles Assisted Targeted Phytoconstituent Delivery for Dermatological Disorders 自然的智能刺：利用微针辅助靶向植物成分递送皮肤疾病

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2026-01-08 DOI: 10.1208/s12249-025-03311-4

Akshay Kumar, Suresh Babu Kondaveeti, Arpan Kumar Tripathi, Mohit Agrawal, Thakur Gurjeet Singh, Devesh Kumar, Mohit Kumar

Microneedle-mediated transdermal delivery of phytoconstituents represents a sophisticated and emerging paradigm in dermatological therapeutics, bridging the pharmacological efficacy of plant-derived bioactive with the precision of advanced biomedical engineering. Conventional topical dosage forms are often constrained by the formidable barrier function of the stratum corneum, instability of phytochemicals, and suboptimal patient adherence. Microneedle arrays circumvent these limitations by creating transient microchannels that enable minimally invasive, painless, and controlled delivery of therapeutics into the viable epidermal and dermal layers. The bioactive compounds such as curcumin, resveratrol, asiaticoside, and glycyrrhizin exhibit multifaceted pharmacological activities, including anti-inflammatory, antioxidant, antimicrobial, and pro-regenerative effects, which are beneficial for the management of cutaneous pathologies such as psoriasis, eczema, acne vulgaris, and chronic ulcerations. The incorporation of these phytoconstituents into dissolving or hydrogel-forming microneedles enhances their physicochemical stability, facilitates sustained and localized drug release, and minimizes systemic exposure, thereby improving therapeutic efficacy and safety. The utilization of natural, biodegradable, and biocompatible polymers such as chitosan, hyaluronic acid, silk fibroin, and alginate, further augments the structural integrity and bioperformance of microneedle systems while aligning with eco-sustainable pharmaceutical design principles. This integrative strategy signifies a pivotal advancement toward personalized dermatological interventions, enabling precise dosing and targeted pharmacokinetics. The future research should emphasize material innovation, in vivo pharmacodynamic assessment, and large-scale translational studies to validate the clinical potential of phytoconstituent-loaded microneedles as next-generation bioresponsive platforms for skin therapeutics.

Graphical Abstract

微针介导的植物成分透皮给药代表了皮肤科治疗中一种复杂和新兴的范例，将植物源性生物活性的药理功效与先进生物医学工程的精确性联系起来。传统的外用剂型常常受到角质层强大的屏障功能、植物化学物质的不稳定性以及患者依从性欠佳的限制。微针阵列通过创建瞬时微通道来规避这些限制，从而实现微创、无痛和可控地将治疗药物输送到可存活的表皮和真皮层。姜黄素、白藜芦醇、积雪草苷和甘草酸等生物活性化合物具有多方面的药理活性，包括抗炎、抗氧化、抗菌和促再生作用，对牛皮癣、湿疹、寻常痤疮和慢性溃疡等皮肤疾病的治疗有益。将这些植物成分掺入溶解性或水凝胶形成的微针中可以增强其物理化学稳定性，促进持续和局部药物释放，并最大限度地减少全身暴露，从而提高治疗疗效和安全性。利用天然、可生物降解和生物相容性聚合物，如壳聚糖、透明质酸、丝素蛋白和海藻酸盐，进一步增强了微针系统的结构完整性和生物性能，同时符合生态可持续的药物设计原则。这种综合策略标志着个性化皮肤病学干预的关键进步，使精确的剂量和靶向药代动力学成为可能。未来的研究应强调材料创新、体内药效学评估和大规模转化研究，以验证植物成分负载微针作为下一代皮肤治疗生物反应平台的临床潜力。图形抽象

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引用次数: 0

Amphotericin B-Loaded Bigel: Characterization and in vivo Antileishmanial Evaluation in BALB/c Mice Infected with Leishmania amazonensis 两性霉素b负载Bigel: BALB/c小鼠感染亚马逊利什曼原虫的特性和体内抗利什曼原虫的评价

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2026-01-08 DOI: 10.1208/s12249-025-03303-4

Rosilene Ribeiro de Sousa, Matheus Oliveira do Nascimento, Leandro Josuel da Costa Santos, Francisco Gesley de Sousa Abreu, André Luiz Pinheiro de Moura, Daniele Costa Lopes, Karla Germana dos Reis Bacelar, Rita de Cássia Vianna de Carvalho, Paulline Paiva Mendes de Souza Leal, Charllyton Luis Sena da Costa, Vitória de Cássia Coelho Rodrigues, Fernando Aécio de Amorim Carvalho, Michel Muálem de Moraes Alves, André Luis Menezes Carvalho

American Tegumentary Leishmaniasis (ATL) is a zoonotic disease characterized by polymorphic cutaneous and mucosal manifestations, caused by protozoa of the genus Leishmania and transmitted through the bite of sandflies. Current treatment relies on pharmacotherapy with drugs such as amphotericin B (AmB), which is limited by adverse effects. Novel topical formulations of AmB, including bigels, have been investigated as alternatives for ATL therapy, aiming to achieve local efficacy with reduced toxicity and lower cost. This study sought to develop and characterize an AmB loaded-bigel for topical application and to evaluate its in vivo antileishmanial activity. The formulations were characterized by organoleptic analysis, pH, stability, oil retention capacity, swelling, spreadability, and texture profile. In vitro drug release and skin permeation were assessed using Franz diffusion cells and murine skin, while the ocular irritation potential was evaluated through the HET-CAM assay. In vivo efficacy was tested in BALB/c mice infected with Leishmania amazonensis, monitoring lesion progression and parasite burden. Treatment with the AmB loaded-bigel resulted in a 74.1% reduction in parasite load. Overall, the bigel demonstrated favorable physicochemical properties, stability, spreadability, and controlled release of AmB. The in vivo findings highlight its promising antileishmanial activity and support the potential of AmB-loaded bigels as a therapeutic alternative for ATL.

Graphical Abstract

美洲背囊利什曼病（ATL）是一种人畜共患疾病，其特征是皮肤和粘膜表现多形性，由利什曼属原生动物引起，通过白蛉叮咬传播。目前的治疗依赖于药物治疗，如两性霉素B (AmB)，其副作用有限。包括bigels在内的新型AmB外用制剂已被研究作为ATL治疗的替代方案，旨在以更低的毒性和更低的成本实现局部疗效。本研究旨在开发和表征一种局部应用的AmB负载bigel，并评估其体内抗利什曼原虫活性。通过感官分析、pH值、稳定性、保油能力、溶胀性、涂抹性和质地特征对配方进行了表征。采用Franz扩散细胞法和小鼠皮肤法评估体外药物释放和皮肤渗透，并通过ht - cam法评估眼部刺激电位。在感染亚马逊利什曼原虫的BALB/c小鼠中检测其体内疗效，监测病变进展和寄生虫负荷。用AmB -bigel处理可使寄生虫载量降低74.1%。总体而言，该凝胶具有良好的理化性质、稳定性、展布性和AmB的控释性。在体内的研究结果突出了其有希望的抗利什曼活性，并支持了amb负载bigels作为ATL治疗替代方案的潜力。图形抽象

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引用次数: 0

Development, Stability, and Clinical Efficacy of an Oil-in-Serum Formulation with Olive Extract Standardized in Hydroxytyrosol for Post-Inflammatory Hyperpigmentation Treatment 羟酪醇标准橄榄提取物血清油配方用于炎症后色素沉着治疗的开发、稳定性和临床疗效

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2026-01-08 DOI: 10.1208/s12249-025-03318-x

B. J. Navarro, L. Kakuda, P. M. B. G. Maia Campos

Post-inflammatory hyperpigmentation (PIH) is a prevalent dermatological condition arising from inflammatory processes that significantly impacts quality of life. Natural alternatives to conventional treatments are increasingly sought to minimize adverse effects while maintaining efficacy. This study aimed to develop and evaluate an innovative oil-in-serum formulation containing olive extract standardized in hydroxytyrosol (HT) for PIH treatment, assessing its stability, sensory properties, and clinical efficacy. Two complementary formulations were developed: a hydroxyethylcellulose-based gel (with/without 0.1% olive extract containing 20% HT) and an olive oil-based formulation. Stability tests, texture analysis, sensory evaluation and clinical efficacy analysis in participants with PIH were conducted. Overall, the formulations were stable and showed favorable sensory properties. The oil-in-serum system exhibited enhanced spreadability, hydration perception, and reduced stickiness compared to individual components. After 45 days of application, the formulation with HT increased stratum corneum water content and reduced transepidermal water loss (TEWL), indicating improved skin barrier function. A significant reduction in color difference between lesional and perilesional areas was observed in high-resolution imaging analysis, showing a reduction in the PIH. Participants reported enhanced skin hydration and reduced dark spots, which corroborate the instrumental measurements results. Finally, the oil-in-serum formulation with olive extract standardized in HT proved effective for PIH treatment, combining excellent sensory properties with clinical efficacy in improving skin hydration, barrier function, and hyperpigmentation control.

Graphical Abstract

炎症后色素沉着（PIH）是一种常见的皮肤病，由炎症过程引起，严重影响生活质量。人们越来越多地寻求传统疗法的天然替代品，以尽量减少副作用，同时保持疗效。本研究旨在开发和评估一种创新的血清油配方，该配方含有标准化的橄榄提取物羟酪醇（HT），用于治疗PIH，评估其稳定性、感官特性和临床疗效。开发了两种互补配方：基于羟乙基纤维素的凝胶（含/不含含20% HT的0.1%橄榄提取物）和基于橄榄油的配方。对PIH患者进行稳定性试验、质地分析、感觉评价和临床疗效分析。总体而言，该配方稳定且具有良好的感官性能。与单个成分相比，血清油系统表现出增强的涂抹性、水合感和降低的粘性。使用45天后，含HT的配方增加了角质层含水量，减少了经皮失水（TEWL），表明皮肤屏障功能得到改善。在高分辨率成像分析中观察到病变区域和病变周围区域之间的色差显著减少，显示PIH减少。参与者报告皮肤水合作用增强，黑斑减少，这证实了仪器测量结果。最后，在HT中标准化的橄榄提取物血清油配方被证明是有效的PIH治疗，结合了优异的感官特性和改善皮肤水合，屏障功能和控制色素沉着的临床疗效。图形抽象

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引用次数: 0

Optimization of Ionic Liquid Based NLC for Nose-To-Brain Delivery of Tetrabenazine Hydrochloride 离子液体NLC对盐酸丁苯那嗪鼻脑给药的优化研究

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2026-01-08 DOI: 10.1208/s12249-025-03313-2

Namdeo R. Jadhav, Sonali R. Yede, Asha S. Jadhav, Megha N. Mane, Prathamesh S. Patil, Suhas S. Mohite

Nanostructured lipid carriers (NLCs) have been researched extensively for nose-to-brain drug delivery but are often constrained by low drug solubility, limited payload, and poor permeability. Herein, we have developed Hybrid NLCs (Liquid lipid replaced with bioionic liquid) to enhance drug solubility, permeability, payload, and nose-to-brain bioavailability of Tetrabenazine hydrochloride (TBZ), a BCS-class IV drug. The formulation and optimization of the Hybrid-NLCs was carried out using a central composite design, followed by loading into an in-situ gel. The optimized TBZ Hybrid-NLCs demonstrated a particle size of 149.84 ± 0.73 nm, PDI 0.33 ± 0.01, zeta potential -38.96 ± 0.09 mV, and % Entrapment efficiency 97.65 ± 0.70%. The % Drug loading of TBZ in Hybrid-NLCs was significantly higher (34.4 ± 0.98%) compared to 28.2 ± 0.54% in conventional or Plain NLCs, reflecting superior drug-loading (p < 0.05). Comparative in-vitro and ex-vivo drug release studies revealed improved TBZ release (74.22 ± 0.20% in-vitro, and 74.73 ± 0.64% ex-vivo) from Hybrid-NLCs, compared to the Plain-NLCs (66.44 ± 0.21% in-vitro and 61.18 ± 0.39% ex-vivo). Intranasal administration of TBZ-loaded-Hybrid-NLC gels in Wistar rats showed C_max 7.87 ± 0.80 µg/ml and T_max 5–6 h in brain tissue, outperforming (Plain-NLC), achieving C_max 6.32 ± 0.30 µg/ml and a similar T_max. Conclusively, the nose-to-brain delivery of TBZ-loaded Hybrid-NLCs gel significantly enhanced TBZ bioavailability to the brain, 1.51-fold over Plain-NLCs gel. Findings underscored Hybrid-NLCs as a promising non-invasive strategy for enhancing the bioavailability of BCS class IV drugs via nose to brain delivery, prospective in the treatment of neurological diseases/disorders.

Graphical Abstract

纳米结构脂质载体（nlc）已经被广泛研究用于鼻子到大脑的药物递送，但通常受到药物溶解度低、有效载荷有限和渗透性差的限制。在此，我们开发了混合型NLCs（用生物离子液体代替液体脂质）来提高盐酸Tetrabenazine （TBZ）的药物溶解度、渗透性、有效载荷和鼻-脑生物利用度，这是一种bcs类IV药物。Hybrid-NLCs的配方和优化采用中心复合设计，然后加载到原位凝胶中。优化后的TBZ Hybrid-NLCs粒径为149.84±0.73 nm， PDI为0.33±0.01，zeta电位为-38.96±0.09 mV，捕集效率为97.65±0.70%。混合NLCs中TBZ的载药量百分比（34.4±0.98%）显著高于常规NLCs和普通NLCs的28.2±0.54%，反映出更高的载药量（p < 0.05）。体外和离体药物释放对比研究显示，Hybrid-NLCs的TBZ释放量（体外74.22±0.20%，离体74.73±0.64%）高于plains - nlcs（体外66.44±0.21%，离体61.18±0.39%）。经鼻给药后，Wistar大鼠脑组织Cmax为7.87±0.80µg/ml， Tmax为5 ~ 6 h，优于Plain-NLC， Cmax为6.32±0.30µg/ml， Tmax相似。最后，负载TBZ的混合型nlcs凝胶经鼻至脑给药可显著提高TBZ在脑内的生物利用度，是普通型nlcs凝胶的1.51倍。研究结果强调，Hybrid-NLCs是一种有前途的非侵入性策略，可通过鼻到脑给药提高BCS IV类药物的生物利用度，在神经系统疾病/障碍的治疗中具有前景。图形抽象

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引用次数: 0

Meloxicam Eluting 3D Printed 316L Stainless Steel Implants for Targeted Delivery in Bone Fixation Surgeries 美洛昔康洗脱3D打印316L不锈钢植入物用于骨固定手术的靶向递送

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2026-01-08 DOI: 10.1208/s12249-025-03294-2

Manjusha Annaji, Ishwor Poudel, Nur Mita, Chu Zhang, Humaira Yeasmin, Seungjong Lee, Peter Panizzi, Robert D. Arnold, Amal Kaddoumi, Nima Shamsaei, Byron Farnum, Oladiran Fasina, R. Jayachandra Babu

Implant failures in orthopedic surgeries can occur due to inflammation, poor osteointegration, and biofilm formation. The local delivery of anti-inflammatory drugs is one of the potential solutions to address orthopedic implant failures caused by extensive inflammation, poor osteointegration, and biofilm formation. This study utilized a simple spray coating technique to deposit multilayer coatings of the anti-inflammatory drug meloxicam and PLGA on 3D printed 316L stainless steel implants. The implants were evaluated for their drug content, drug-polymer miscibility, static contact angle, corrosion resistance, in vitro release, cell adhesion, cell proliferation, and bacterial adhesion studies. The coatings aimed to improve osteointegration and reduce biofilm formation. The drug release studies demonstrated an initial burst release accompanied by sustained release for more than 30 days. The meloxicam-PLGA coated implants showed higher resistance to pitting corrosion, improved adhesion, and proliferation of human U2OS cells in comparison to uncoated implants. In addition, results from cell cytotoxicity studies confirmed that all the coatings are biocompatible and safe for in vivo application. The meloxicam-PLGA coated implants were also found to have significantly lower bacterial adhesion and biofilm formation compared to uncoated implants for both S. aureus (p < 0.01) and S. pseudintermedius (p < 0.01). The multilayer coatings developed in this study have the potential to improve adhesion at the implant-bone interface and thus might prevent implant rejections in patients undergoing orthopedic surgery. Moreover, this method can be applied to other drugs and polymers to address the issues related to implant failure, pain management, and surgical site infections.

Graphical Abstract

在骨科手术中，由于炎症、骨整合不良和生物膜的形成，植入物可能会失败。抗炎药物的局部递送是解决由广泛炎症、骨整合不良和生物膜形成引起的骨科植入物失败的潜在解决方案之一。本研究采用简单的喷涂技术，在3D打印的316L不锈钢植入体上沉积消炎药物美洛昔康和PLGA的多层涂层。评估植入物的药物含量、药物-聚合物混溶性、静态接触角、耐腐蚀性、体外释放、细胞粘附、细胞增殖和细菌粘附研究。该涂层旨在改善骨整合并减少生物膜的形成。药物释放研究表明，最初的爆发释放伴随着持续释放超过30天。与未包被的植入物相比，美洛昔康- plga包被的植入物具有更高的抗点蚀性、更好的附着力和人类U2OS细胞的增殖能力。此外，细胞毒性研究的结果证实，所有的涂层是生物相容性和安全的体内应用。与未包被的金黄色葡萄球菌（p < 0.01）和假中间葡萄球菌（p < 0.01）相比，美洛昔康- plga包被的种植体对细菌的粘附和生物膜的形成也显著降低。本研究中开发的多层涂层有可能改善种植体-骨界面的粘附性，从而可能防止骨科手术患者的种植体排斥反应。此外，该方法可应用于其他药物和聚合物，以解决与植入失败，疼痛管理和手术部位感染相关的问题。图形抽象

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引用次数: 0

ML-Driven Pharmaceutical Cocrystal Technology: Advances in Screening, Property Prediction and Applications 机器学习驱动的药物共晶技术：筛选、性能预测及应用进展

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2026-01-08 DOI: 10.1208/s12249-025-03266-6

Qian Ye, Sheng Wang, Zhaoyang Zhang

Recently, pharmaceutical cocrystal technology has garnered considerable global attention because of its innovativeness and environmental sustainability. This technology effectively enhances the bioavailability of poorly soluble drugs and optimizes their physicochemical and biological properties. Considering the pivotal role of cocrystal screening in improving drug bioavailability, herein, we develop a comprehensive framework for understanding the definition, screening, key characteristics, and applications of drug cocrystals in contemporary drug development. We discuss a series of innovative and efficient screening methods, such as high-throughput computational screening, artificial intelligence screening, and Raman spectroscopy, focusing particularly on the application of machine learning (ML) algorithms. Such algorithms can analyze large volumes of physicochemical data for virtual cocrystal screening and solubility prediction. Compared with traditional experimental screening methods—such as X-ray diffraction, thermal analysis (TA), and high-performance liquid chromatography (HPLC), ML models can manage high workload, address gaps in screening, and facilitate accurate solubility prediction. By using ML models, researchers can narrow the experimental scope and accelerate the discovery and development of novel drug cocrystals. This approach holds promise for enhancing drug efficacy, reducing adverse reactions, and improving patient compliance. Future studies should integrate experimental and virtual screening methods to enhance the efficiency and accuracy of cocrystal selection.

Graphical Abstract

近年来，医药共晶技术因其创新性和环境可持续性而受到全球广泛关注。该技术有效地提高了难溶性药物的生物利用度，优化了其理化和生物学特性。考虑到共晶筛选在提高药物生物利用度方面的关键作用，本文建立了一个全面的框架，以了解药物共晶的定义、筛选、关键特征以及在当代药物开发中的应用。我们讨论了一系列创新和高效的筛选方法，如高通量计算筛选、人工智能筛选和拉曼光谱，特别关注机器学习（ML）算法的应用。这种算法可以分析大量的物理化学数据，用于虚拟共晶筛选和溶解度预测。与传统的实验筛选方法（如x射线衍射、热分析（TA）和高效液相色谱（HPLC））相比，ML模型可以管理高工作量，解决筛选中的空白，并促进准确的溶解度预测。通过使用ML模型，研究人员可以缩小实验范围，加速新型药物共晶的发现和开发。这种方法有望提高药物疗效，减少不良反应，提高患者的依从性。未来的研究应将实验筛选和虚拟筛选相结合，以提高共晶筛选的效率和准确性。图形抽象

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引用次数: 0

Preclinical Toxicity and Pharmacokinetic Evaluation of Paclitaxel Nanodispersion 紫杉醇纳米分散体的临床前毒性和药代动力学评价。

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2025-12-18 DOI: 10.1208/s12249-025-03268-4

Ajay J. Khopade, Malay D. Shah, Bhushan S. Borole, Bharat Patel, Bharat Pateliya, Vinod Burade

This study evaluates the safety, tolerability, pharmacokinetics, and tissue distribution of paclitaxel injection concentrate for nanodispersion (PICN), either as standalone treatment or in comparison with Abraxane® (AbX) and Oncotaxel (OtX, generic formulation of Taxol® from Sun Pharma). In vitro cytotoxicity was assessed in—HT-29, PC-3, SKOV3 and NCI H522 human cancer cell lines. Single- and multiple-dose toxicity studies were conducted in rodents evaluating clinical signs, hematology, histopathology, and organ-specific toxicity. Pharmacokinetic studies were performed in rats analyzing Paclitaxel (PtX) concentrations by LC–MS/MS. PICN demonstrated comparable in vitro cytotoxicity to OtX. Single- and repeat-dose toxicity studies revealed that PICN has similar toxicity profile with AbX, including reversible lymphoid depletion and irreversible testicular toxicity at higher doses. Known PtX class effects, myelosuppression and neuropathy was observed in both PICN and reference groups; with less pronounced effects in females. PICN (at 10 mg/kg) produced a lower reduction in pain threshold (~ 22%) compared to OtX (~ 43%), suggesting a reduced potential for neurotoxicity. PICN showed no local irritation following IV administration and no hemolytic potential in-vitro. It exhibited dose-proportional increases in C_max and AUC_0–inf across 5–20 mg/kg, with pharmacokinetic parameters comparable to AbX. Red blood cell (RBC) partitioning studies indicated balanced distribution for PICN compared to OtX, and slightly lower RBC exposure than AbX. PICN also demonstrated moderate PtX distributions with concentrations higher than AbX but substantially lower than OtX in various tissues. Collectively, these results support PICN as a promising alternative, combining favorable safety and comparable pharmacokinetics.

Graphical Abstract

本研究评估了紫杉醇注射浓缩物用于纳米分散体（PICN）的安全性、耐受性、药代动力学和组织分布，无论是单独治疗还是与Abraxane®（AbX）和Oncotaxel （OtX，太阳制药紫杉醇®的通用配方）进行比较。对ht -29、PC-3、SKOV3和NCI H522人癌细胞进行体外细胞毒性评价。在啮齿动物中进行了单剂量和多剂量毒性研究，评估临床症状、血液学、组织病理学和器官特异性毒性。采用LC-MS/MS对大鼠进行了紫杉醇（PtX）浓度的药代动力学研究。PICN显示出与OtX相当的体外细胞毒性。单剂量和重复剂量毒性研究表明，PICN与AbX具有相似的毒性特征，包括高剂量时可逆的淋巴细胞耗竭和不可逆的睾丸毒性。已知的PtX类效应、骨髓抑制和神经病变在PICN组和参照组均有观察；对女性的影响不那么明显。与OtX（~ 43%）相比，PICN （10 mg/kg）产生的痛阈降低（~ 22%）较低，表明神经毒性可能降低。PICN在静脉给药后无局部刺激，体外无溶血潜能。Cmax和AUC0-inf在5-20 mg/kg范围内呈剂量比例增加，药代动力学参数与AbX相当。红细胞（RBC）分配研究表明，与OtX相比，PICN分布平衡，RBC暴露量略低于AbX。在不同组织中，PICN也表现出适度的PtX分布，其浓度高于AbX，但明显低于OtX。总的来说，这些结果支持PICN作为一个有希望的替代方案，具有良好的安全性和相似的药代动力学。

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引用次数: 0

New Strategies to Improve Drug Solubility and Its Impact on Bioavailability: A Patent Review (2015–2024) 提高药物溶解度及其对生物利用度影响的新策略：专利审查（2015-2024）。

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2025-12-17 DOI: 10.1208/s12249-025-03287-1

Andrés Felipe Pérez Palacios, Jorge Alexis Medina Parra, Daniel Santiago Córdoba Velasco, Diana Carolina Zona Rubio, Izabel Almeida Alves, Diana Marcela Aragón Novoa

Poor aqueous solubility is a major barrier in drug development, affecting dissolution, absorption, and systemic bioavailability. Nearly 40% of approved drugs and up to 90% of new chemical entities face this limitation, resulting in therapeutic inefficacy and costly clinical development. This study reviewed patents published between 2015 and 2024 that describe technological strategies to enhance drug solubility and bioavailability, aiming to identify innovation trends and their pharmaceutical impact. A structured search was conducted in the Espacenet database using the keywords “bioavailability” and “solubility” under the IPC code A61K. From 98,111 initial results, duplicates, language restrictions, and patents related to cosmetics, nutrition, or veterinary products were excluded, yielding 29 eligible documents. Extracted data included applicant country, therapeutic indication, BCS classification, formulation approach, manufacturing method, and available in vivo pharmacokinetic results. Descriptive analysis was performed using R software. China led patent registrations (55%), followed by the USA (17%). Patent filings increased steadily from 2016–2020, decreased during the COVID-19 pandemic, and recovered after 2021. Most drugs belonged to BCS Class II (76%), reflecting high permeability but poor solubility. The main strategies included particle size reduction, solid dispersions, self-emulsifying drug delivery systems, cyclodextrin inclusion complexes, and advanced crystallization techniques. When reported, pharmacokinetic data showed significant improvements in Cmax and AUC; however, only 58% of patents included in vivo studies. Overall, patents reveal robust innovation aimed at overcoming solubility challenges.

Graphical Abstract

水溶性差是药物开发的主要障碍，影响药物的溶解、吸收和全身生物利用度。近40%的批准药物和高达90%的新化学实体面临这一限制，导致治疗无效和昂贵的临床开发。本研究回顾了2015年至2024年间发表的专利，这些专利描述了提高药物溶解度和生物利用度的技术策略，旨在确定创新趋势及其对制药的影响。在Espacenet数据库中使用关键词“生物利用度”和“溶解度”进行结构化检索，IPC代码为A61K。从98,111个初步结果中，排除了与化妆品、营养品或兽药相关的重复、语言限制和专利，产生了29个符合条件的文件。提取的数据包括申请人国家、治疗适应症、BCS分类、配方方法、制造方法和体内药代动力学结果。采用R软件进行描述性分析。中国的专利注册量领先（55%），其次是美国（17%）。专利申请量在2016-2020年期间稳步增长，在COVID-19大流行期间下降，并在2021年之后恢复。大多数药物属于BCS II类（76%），反映高通透性但溶解度差。主要策略包括粒径减小、固体分散、自乳化给药系统、环糊精包合物和先进的结晶技术。报告时，药代动力学数据显示Cmax和AUC显著改善；然而，只有58%的专利包括体内研究。总的来说，专利揭示了旨在克服溶解度挑战的强大创新。

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引用次数: 0

Improved Oral Bioavailability and Brain Distribution of Hesperidin via Cochleate Formulation: Statistical Optimization and Pharmacokinetic Study 通过Cochleate配方改善橙皮苷的口服生物利用度和脑分布：统计优化和药代动力学研究。

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2025-12-17 DOI: 10.1208/s12249-025-03297-z

Komaldeep Kaur, Yogesh A. Kulkarni, Sarika Wairkar

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.

Graphical Abstract

橙皮苷是一种黄酮，具有抗氧化、抗炎和抗淀粉样变性的特性，是治疗阿尔茨海默病的有希望的候选药物。橙皮苷溶解度差，口服生物利用度低

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引用次数: 0

Exploring the Co-delivery of Sorafenib and Venetoclax to Induce Ferroptosis and Apoptosis Mediated Cancer Cell Death using Surface Modified PLGA Nanoparticles 利用表面修饰的PLGA纳米颗粒，探索索拉非尼和Venetoclax共同递送诱导铁凋亡和凋亡介导的癌细胞死亡。

IF 4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech

Pub Date : 2025-12-17 DOI: 10.1208/s12249-025-03304-3

Dhruv Patel, Smriti Bhardwaj, Vivek Yadav, Kaushik Kuche, Pratik Dhake, Sanyog Jain

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.

Graphical Abstract

化疗耐药仍然是肿瘤治疗的一个深刻障碍，而具有不同作用机制的化疗药物的联合递送提供了一种有效的方法。在本研究中，我们开发了聚乳酸-羟基乙酸（PLGA）纳米颗粒（NPs），其上装载了Sorafenib (SOR)，一种铁凋亡诱导剂，和Venetoclax (VTX)，一种细胞凋亡诱导剂，用于联合细胞死亡。这些PLGA(SOR + VTX) NPs通过纳米沉淀法制备，然后用聚多巴胺（PDA）和牛血清白蛋白（BSA）连续涂覆。PDA被用来促进BSA的连接，而BSA则可以靶向albondin和分泌酸性且富含半胱氨酸（SPARC）受体的蛋白。BSA-PDA-PLGA（SOR + VTX）纳米粒子呈球形，尺寸为183.6±6.20 nm， PDI为0.108±0.02，z电位为-23.3±1.03 mV， SOR和VTX呈1:1比例加载。纳米颗粒表现出缓释行为，并被评估为血液相容性。细胞摄取研究反映了更好的细胞质内化，与MDA-MB-231、A549和HeLa细胞系中SOR + VTX的物理组合相比，该配方的IC50值分别降低了2.74、3.40和2.90倍。MDA-MB-231、A549和HeLa细胞的凋亡指数分别比SOR + VTX高1.42倍、1.40倍和1.40倍。此外，BSA-PDA-PLGA(SOR + VTX) NPs诱导活性氧的产生和线粒体膜电位的去极化。他们还通过在所有细胞系中消耗谷胱甘肽和升高丙二醛水平证明了铁下垂的升级。因此，通过BSA-PDA-PLGA NP共同递送SOR和VTX在针对不同肿瘤细胞时表现出协同活性。

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引用次数: 0