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Current Advancements on Oral Protein and Peptide Drug Delivery Approaches to Bioavailability: Extensive Review on Patents 口服蛋白质和肽类给药生物利用度方法的最新进展:专利综述
Pub Date : 2024-07-22 DOI: 10.2174/0126673878299775240719061653
Prasanna Parida, A. K. Prusty, S. Patro, B. R. Jena
Protein and peptide-based drugs have greater therapeutic efficacy and potential applicationand lower toxicity compared to chemical entities in long-term use within optimum concentrationas they are easily biodegradable due to biological origin. While oral administration is preferable,most of these substances are currently administered intravenously or subcutaneously. This isprimarily due to the breakdown and poor absorption in the GI tract. Hence, ongoing research is focusedon investigating absorption enhancers, enzyme inhibitors, carrier systems, and stability enhancersas potential strategies to facilitate the oral administration of proteins and peptides. Investigationshave been directed towards advancing novel technologies to address gastrointestinal (GI)barriers associated with protein and peptide medications. The current review intensifies formulationand stability approaches for oral protein & peptide drug delivery systems with all significant parametersintended for patient safety. Notably, certain innovative technologies have been patentedand are currently undergoing clinical trials or have already been introduced into the market. All theapproaches stated for the administration of protein and peptide drugs are critically discussed, havingtheir current status, future directions, and recent patents published in the last decades.
与化学物质相比,蛋白质和肽类药物具有更高的疗效和潜在的应用价值,在最佳浓度内长期使用时毒性较低,因为它们源于生物,易于生物降解。虽然口服给药更为可取,但目前大多数此类物质都是静脉注射或皮下注射。这主要是由于这些物质在消化道内分解和吸收较差。因此,目前的研究重点是研究吸收促进剂、酶抑制剂、载体系统和稳定性增强剂,这些都是促进蛋白质和肽口服给药的潜在策略。研究的方向是开发新型技术,以解决与蛋白质和肽类药物相关的胃肠道(GI)障碍。本综述深入探讨了口服蛋白质和肽类给药系统的配方和稳定性方法,以及所有旨在保障患者安全的重要参数。值得注意的是,某些创新技术已经申请了专利,目前正在进行临床试验或已经投放市场。该书对所有用于蛋白质和肽类药物给药的方法进行了批判性讨论,包括其现状、未来发展方向以及过去几十年中最新发布的专利。
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引用次数: 0
Nanocarriers for Cannabinoid Delivery: Enhancing Therapeutic Potential 用于大麻素递送的纳米载体:提高治疗潜力
Pub Date : 2024-07-22 DOI: 10.2174/0126673878300347240718100814
Varun Singh, Samar Vihal, Rupali Rana, Charul Rathore
Medical cannabis has potential therapeutic benefits in managing pain, anxiety, depression, and neurological and movement disorders. Phytocannabinoids derived from the cannabis plantare responsible for their pharmacological and therapeutic properties. However, the complexity ofcannabis components, especially cannabinoids, poses a challenge to effective medicinal administration. Even with the increasing acceptance of cannabis-based medicines, achieving consistent bioavailability and targeted distribution remains difficult. Conventional administration methods areplagued by solubility and absorption problems requiring innovative solutions. After conducting athorough review of research papers and patents, it has become evident that nanotechnology holdsgreat promise as a solution. The comprehensive review of 36 research papers has yielded valuableinsights, with 7 papers reporting enhanced bioavailability, while others have focused on improvements in release, solubility, and stability. Additionally, 19 patents have been analyzed, of which 7specifically claim enhanced bioavailability, while the remaining patents describe various formulation methods. These patents outline effective techniques for encapsulating cannabis using nanocarriers, effectively addressing solubility and controlled release. Studies on the delivery of cannabisusing nanocarriers focus on improving bioavailability, prolonging release, and targeting specific areas. This synthesis highlights the potential of nanotechnology to enhance cannabis therapies andpave the way for innovative interventions and precision medicine.
医用大麻在控制疼痛、焦虑、抑郁以及神经和运动障碍方面具有潜在的治疗功效。从大麻植物中提取的植物大麻素具有药理和治疗特性。然而,大麻成分(尤其是大麻素)的复杂性给有效用药带来了挑战。即使人们对以大麻为基础的药物的接受度越来越高,但要实现一致的生物利用度和有针对性的分布仍然十分困难。传统给药方法存在溶解和吸收问题,需要创新的解决方案。在对研究论文和专利进行全面审查后,纳米技术显然是一种大有可为的解决方案。对 36 篇研究论文的全面审查得出了宝贵的见解,其中 7 篇论文报告了生物利用度的提高,其他论文则侧重于释放、溶解度和稳定性的改善。此外,还对 19 项专利进行了分析,其中 7 项专利明确声称提高了生物利用度,其余专利则描述了各种制剂方法。这些专利概述了使用纳米载体封装大麻的有效技术,有效地解决了溶解性和控释问题。利用纳米载体输送大麻的研究主要集中在提高生物利用率、延长释放时间和针对特定区域。本综述强调了纳米技术在增强大麻疗法方面的潜力,并为创新干预和精准医疗铺平了道路。
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引用次数: 0
Optimizing Microfluidic Channel Design with High-Performance Materials for Safe Neonatal Drug Delivery 利用高性能材料优化微流控通道设计,实现新生儿安全给药
Pub Date : 2024-07-19 DOI: 10.2174/0126673878292962240718055526
T. Archana, N. Nachammai, S. Praveenkumar
Designing the microfluidic channel for neonatal drug delivery requiresproper considerations to enhance the efficiency and safety of drug substances when used in neonates.Thus, this research aims to evaluate high-performance materials and optimize the channel designby modeling and simulation using COMSOL multiphysics in order to deliver an optimum flowrate between 0. 3 and 1 mL/hr.Some of the materials used in the study included PDMS, glass, COC, PMMA, PC, TPE,and hydrogels, and the evaluation criterion involved biocompatibility, mechanical properties, chemicalresistance, and ease of fabrication. The simulation was carried out in the COMSOL multiphysicsplatform and demonstrated the fog fluid behavior in different channel geometries, includinglaminar flow and turbulence. The study then used systematic changes in design parameters with theaim of establishing the best implementation models that can improve the efficiency and reliabilityof the drug delivery system. The comparison was based mostly on each material and its appropriatenessin microfluidic usage, primarily in neonatal drug delivery. The biocompatibility of the developedmaterials was verified using the literature analysis and adherence to the ISO 10993 standard,thus providing safety for the use of neonatal devices. Tensile strength was included to checkthe strength of each material to withstand its operation conditions. Chemical resistance was alsotested in order to determine the compatibility of the materials with various drugs, and the possibilityof fabrication was also taken into consideration to identify appropriate materials that could be usedin the rapid manufacturing of the product.The results we obtained show that PDMS, due to its flexibility and simplicity in simulationcoupled with more efficient channel designs which have been extracted from COMSOL, present afeasible solution to neonatal drug delivery.The present comparative study serves as a guide on the choice of materials and designof microfluidic devices to help achieve safer and enhanced drug delivery systems suitable for thedelicate reception of fragile neonates.
因此,本研究旨在评估高性能材料,并通过 COMSOL 多物理场建模和仿真优化通道设计,以实现 0.3 至 1 mL/hr 的最佳流速。研究中使用的材料包括 PDMS、玻璃、COC、PMMA、PC、TPE 和水凝胶,评估标准包括生物相容性、机械性能、耐化学性和易制造性。模拟是在 COMSOL 多物理场平台上进行的,演示了不同通道几何形状下的雾状流体行为,包括层流和湍流。然后,该研究系统地改变了设计参数,目的是建立能提高给药系统效率和可靠性的最佳实施模型。比较的主要依据是每种材料及其在微流体中的适用性,主要是在新生儿给药中的适用性。通过文献分析验证了所开发材料的生物相容性,并符合 ISO 10993 标准,从而为新生儿设备的使用提供了安全性。拉伸强度包括检查每种材料在操作条件下的强度。此外,还测试了材料的耐化学性,以确定材料与各种药物的兼容性,并考虑了制造的可能性,以确定可用于快速制造产品的适当材料。我们获得的结果表明,PDMS 因其在模拟方面的灵活性和简易性,再加上从 COMSOL 中提取的更有效的通道设计,为新生儿药物输送提供了可行的解决方案。本比较研究可作为材料选择和微流控装置设计的指南,有助于实现更安全、更先进的药物输送系统,适合脆弱新生儿的精细接收。
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引用次数: 0
Patent Selection: 专利选择:
Pub Date : 2024-03-01 DOI: 10.2174/266738781801240307095846
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引用次数: 0
Navigating the Solution to Drug Formulation Problems at Research andDevelopment Stages by Amorphous Solid Dispersion Technology 用无定形固体分散技术解决研发阶段的药物制剂问题
Pub Date : 2023-12-07 DOI: 10.2174/0126673878271641231201065151
Devika Tripathi, Manjunatha Prabhu B.H, Jagannath Sahoo, Jyoti Kumari
Amorphous Solid Dispersions (ASDs) have indeed revolutionized the pharmaceutical industry, particularly in drug solubility enhancement. The amorphous state of a drug, which is a highenergy metastable state, can lead to an increase in the apparent solubility of the drug. This is due tothe absence of a long-range molecular order, which results in higher molecular mobility and freevolume, and consequently, higher solubility. The success of ASD preparation depends on the selection of appropriate excipients, particularly polymers that play a crucial role in drug solubility andphysical stability. However, ASDs face challenges due to their thermodynamic instability or tendency to recrystallize. Measuring the crystallinity of the active pharmaceutical ingredient (API) anddrug solubility is a complex process that requires a thorough understanding of drug-polymer miscibility and molecular interactions. Therefore, it is important to monitor drug solids closely duringpreparation, storage, and application. Techniques such as solid-state nuclear magnetic resonance(ssNMR), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), Ramanspectroscopy, and dielectric spectroscopy have been successful in understanding the mechanism ofdrug crystallization. In addition, the continuous downstream processing of drug-loaded ASDs hasintroduced new automated methods for consistent ASD production. Advanced techniques such ashot melt extrusion, KinetiSol, electro spraying, and electrospinning have gained popularity. This review provides a comprehensive overview of Amorphous Solid Dispersions (ASDs) for oral drug delivery. It highlights the critical challenges faced during formulation, the impact of manufacturingvariables, theoretical aspects of drug-polymer interaction, and factors related to drug-polymer miscibility. ASDs have been recognized as a promising strategy to improve the oral bioavailability ofpoorly water-soluble drugs. However, the successful development of an ASD-based drug product isnot straightforward due to the complexity of the ASD systems. The formulation and process parameters can significantly influence the performance of the final product. Understanding the interactions between the drug and polymer in ASDs is crucial for predicting their stability and performance.
无定形固体分散体(ASDs)确实彻底改变了制药工业,特别是在药物溶解性增强方面。药物的无定形状态是一种高能亚稳态,可导致药物表观溶解度的增加。这是由于缺乏长程分子序,这导致更高的分子迁移率和自由度,从而具有更高的溶解度。ASD制备的成功取决于合适的辅料的选择,特别是聚合物在药物溶解度和物理稳定性中起着至关重要的作用。然而,asd由于其热力学不稳定性或重结晶倾向而面临挑战。测量活性药物成分(API)的结晶度和药物溶解度是一个复杂的过程,需要对药物-聚合物的混溶性和分子相互作用有透彻的了解。因此,在制备、储存和应用过程中密切监测药物固体是很重要的。固态核磁共振(ssNMR)、衰减全反射傅里叶变换红外光谱(ATR-FTIR)、拉曼光谱和介电光谱等技术已经成功地理解了药物结晶的机制。此外,载药ASD的连续下游加工引入了新的自动化方法,以实现一致的ASD生产。先进的技术,如射熔挤出,KinetiSol,电喷涂和静电纺丝已经得到普及。本文综述了用于口服给药的非晶固体分散体(ASDs)的研究进展。它强调了在配方过程中面临的关键挑战,制造变量的影响,药物-聚合物相互作用的理论方面,以及与药物-聚合物混相相关的因素。asd已被认为是一种很有前途的策略,可以提高低水溶性药物的口服生物利用度。然而,由于ASD系统的复杂性,基于ASD的药物产品的成功开发并不简单。配方和工艺参数对最终产品的性能有显著影响。了解asd中药物和聚合物之间的相互作用对于预测其稳定性和性能至关重要。
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引用次数: 0
In Vivo Evaluation of Chitosan-Titanium Dioxide Nanopowder as Wound Dressing Material. 壳聚糖-二氧化钛纳米粉作为伤口敷料的体内评价。
Pub Date : 2023-09-11 DOI: 10.2174/2667387817666230911115541
Nusaiba Al-Nemrawi, Ruba S Darweesh, Dana Alrousan

Background: Films used for wound healing have many advantages, but should be flexible, robust, adherable and prevent maceration. Both Chitosan (CS) and Titanium dioxide nanopowder (TiO2 NP) have good properties to accelerate wound healing and can be used in preparing films.

Objective: CS and TiO2 NP are combined to formulate films for wound healing. The physical, thermal, chemical, and mechanical characteristics of these films are to be assessed. The antibacterial activity of the films and their performance on wounded rats will be explored.

Methods: Films made of CS and TiO2 NP were characterized by FTIR, TGA, DSC, XRD, and SEM. The films' mechanical characteristics and antimicrobial activity were tested. Films with acceptable mechanical properties were evaluated on rats.

Results: Generally, CS-TiO2 films had higher weight and thickness but lowered flexibility compared to films prepared using CS only. The chosen film showed excellent folding endurance with weight and thickness of around 21.98 mg and 0.16 mm. The surface pH for CS-TiO2 films was acidic, and for the selected film, it was 5.18. CS-TiO2 film was active against all studied bacteria and significantly higher than CS films. The antimicrobial activity of Gram-negative bacteria (P. aeruginosa and E. coli) was higher than that of Gram-positive bacteria (S. aureus). Finally, adding TiO2 NP to the films accelerated the healing process of the created wounds in a murine model, compared to control and CS-treated groups.

Conclusion: Films of TiO2 NP and CS have suitable properties to be used in wound healing and can be further used in the future to load drugs.

背景:用于伤口愈合的薄膜有许多优点,但应具有柔韧性、坚固性、粘附性和防浸渍性。壳聚糖(CS)和二氧化钛纳米粉(TiO2 NP)均具有良好的促进伤口愈合的性能,可用于制备薄膜。目的:将CS与TiO2 NP复合制备伤口愈合膜。要评估这些薄膜的物理、热、化学和机械特性。本文将探讨该膜的抗菌活性及其对受伤大鼠的作用。方法:采用FTIR、TGA、DSC、XRD、SEM对CS和TiO2 NP薄膜进行表征。对膜的力学特性和抗菌活性进行了测试。在大鼠身上对力学性能可接受的薄膜进行了评价。结果:一般来说,CS- tio2薄膜的重量和厚度比仅使用CS制备的薄膜高,但柔韧性较低。所选薄膜的重量和厚度分别为21.98 mg和0.16 mm,具有良好的折叠性能。CS-TiO2薄膜的表面pH值为酸性,所选薄膜的表面pH值为5.18。CS- tio2膜对所研究的细菌均有活性,且活性显著高于CS膜。革兰氏阴性菌(铜绿假单胞菌和大肠杆菌)的抗菌活性高于革兰氏阳性菌(金黄色葡萄球菌)。最后,与对照组和cs处理组相比,在膜中添加TiO2 NP加速了小鼠模型中创面的愈合过程。结论:二氧化钛NP和CS膜具有良好的伤口愈合性能,可进一步用于药物负载。
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引用次数: 0
A Novel Development of Levothyroxine Sodium Orodispersible Mini Tablets for the Treatment of Pediatrics Hypothyroidism. 治疗小儿甲状腺功能减退的左旋甲状腺素钠或分散迷你片的新进展。
Pub Date : 2023-09-08 DOI: 10.2174/2667387817666230908092551
Cecilia Henestrosa, Camila Olivera, Sabrina Flor, Silvia Lucangioli, Ariel Vacatello, Claudia A Ortega, Laura S Favier, Diego A Cifuente

Background: In pediatrics, developing new pharmaceutical forms that offer safety and efficacy is crucial to improve pediatric pharmaceutical care. Orodispersible tablets do not require swallowing because orodispersible tablets dissolve quickly in the mouth, reducing the risk of choking and making medication administration safer and more straightforward. There is no solid dosage form in the pharmaceutical market offering a unit dose of Levothyroxine for pediatric hypothyroidism patients.

Objective: The objective of this study is to design and develop Orodispersible mini tablets of Levothyroxine Sodium (LT4 ODMTs) for pediatric doses.

Methods: LT4 ODMTs were prepared by direct compression with 10 and 15 μg, respectively, using StarLac® and Disolcel® as excipients. United States Pharmacopeia (USP-43) guidelines evaluated and determined pre-compression properties and quality control parameters.

Results: The LT4 ODMTs met the specified limits for quality controls. The Drug Content Uniformity was 97%, Hardness was less than 2.5 N, Friability was less than 0.3%, Disintegration time was less than 25 s, and dissolution profiles (Q 80% > 45 s) followed the USP requirements. Additionally, stability and microbiology assays were realized.

Conclusion: These formulations are optimal for developing new LT4 ODMTs suitable for treating pediatric hypothyroidism.

背景:在儿科,开发安全有效的新剂型是改善儿科药学服务的关键。口服分散片不需要吞咽,因为口服分散片在口腔中迅速溶解,减少了窒息的风险,使药物管理更安全,更直接。在医药市场上没有固体剂型为儿童甲状腺功能减退患者提供单位剂量的左甲状腺素。目的:设计和研制小儿剂量左甲状腺素钠(LT4 ODMTs)口服分散迷你片。方法:以StarLac®和Disolcel®为辅料,分别以10和15 μg直接压缩制备LT4 ODMTs。美国药典(USP-43)指南评估和确定预压缩特性和质量控制参数。结果:LT4 odmt符合规定的质量控制限度。药物含量均匀度97%,硬度小于2.5 N,脆度小于0.3%,崩解时间小于25 s,溶出度(Q 80% > 45 s)符合USP要求。此外,还实现了稳定性和微生物学检测。结论:这些配方是开发适合治疗小儿甲状腺功能减退的新型LT4 ODMTs的最佳选择。
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引用次数: 0
A Critical Appraisal of Lipid Nanoparticles Deployed in Cancer Pharmacotherapy. 脂质纳米颗粒在癌症药物治疗中的应用。
Pub Date : 2023-07-26 DOI: 10.2174/2667387817666230726140745
Santanu Chakraborty, Manami Dhibar, Aliviya Das, Kalpana Swain, Satyanarayan Pattnaik

Treatment modalities of various cancers and the delivery strategies of anticancer agents have evolved significantly in the recent past. The severity and fatality of the disease and hurdles to the effective delivery of therapeutic agents have drawn the attention of researchers across the world for proposing novel and effective drug delivery strategies for anticancer therapeutics. Attempts have been made to propose solutions to the diverse limitations like poor pharmacokinetics and higher systemic toxicities of the traditional delivery of anticancer agents. Nanotechnology-based drug delivery systems including lipid-based nanocarriers have demonstrated significant efficiency in this scenario. The review critically assessed the different types of lipid nanocarrier systems for the effective and optimal delivery of anticancer therapeutic agents. The diverse synthesis approaches are discussed for the laboratory scale and commercial development of different categories of lipid nanocarriers. Further, their application in anticancer drug delivery is illustrated in detail followed by a critical appraisal of their safety and toxicity.

近年来,各种癌症的治疗方式和抗癌药物的递送策略发生了重大变化。这种疾病的严重性和致死率以及治疗药物有效递送的障碍引起了世界各地研究人员的注意,他们提出了新的有效的抗癌药物递送策略。人们已经尝试提出解决各种限制的方法,如传统抗癌药物的药代动力学差和较高的全身毒性。基于纳米技术的药物输送系统,包括基于脂质的纳米载体,在这种情况下已经证明了显著的效率。该综述严格评估了不同类型的脂质纳米载体系统对抗癌治疗剂的有效和最佳递送。讨论了不同种类的脂质纳米载体的实验室规模和商业开发的各种合成方法。此外,详细说明了它们在抗癌药物输送中的应用,随后对它们的安全性和毒性进行了严格的评估。
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引用次数: 0
Patent Selections: 专利的选择:
Pub Date : 2023-06-01 DOI: 10.2174/266738781702231013142408
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引用次数: 0
Meet the Editorial Board Member 与编辑委员会成员见面
Pub Date : 2023-06-01 DOI: 10.2174/266738781702231013122449
Ashok K. Tiwary
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引用次数: 0
期刊
Recent advances in drug delivery and formulation
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