Controlled Drug Delivery Systems: Current Status and Future Directions

The drug delivery system enables the release of the active pharmaceutical ingredient to achieve a desired therapeutic response. Conventional drug delivery systems (tablets, capsules, syrups, ointments, etc.) suffer from poor bioavailability and fluctuations in plasma drug level and are unable to achieve sustained release. Without an efficient delivery mechanism, the whole therapeutic process can be rendered useless. Moreover, the drug has to be delivered at a specified controlled rate and at the target site as precisely as possible to achieve maximum efficacy and safety. Controlled drug delivery systems are developed to combat the problems associated with conventional drug delivery. There has been a tremendous evolution in controlled drug delivery systems from the past two decades ranging from macro scale and nano scale to intelligent targeted delivery. The initial part of this review provides a basic understanding of drug delivery systems with an emphasis on the pharmacokinetics of the drug. It also discusses the conventional drug delivery systems and their limitations. Further, controlled drug delivery systems are discussed in detail with the design considerations, classifications and drawings. In addition, nano-drug delivery, targeted and smart drug delivery using stimuli-responsive and intelligent biomaterials is discussed with recent key findings. The paper concludes with the challenges faced and future directions in controlled drug delivery.     

天然糖类纳米药物传递系统的研究进展

纳米技术作为影响未来人类生活的世界三大新兴科技之一,其与药物传递系统的融合,既可以将药物的药理作用极大限度地发挥出来,又克服了药物本身的局限性.天然糖类的来源十分广泛,不仅价格低廉、无毒性,且具有良好的生物相容性和生物可降解性,被广泛用于纳米药物传递系统.本文对纳米药物传递系统的体系组成进行了归纳,重点阐述了常见糖类及...     

Nano-Drug Delivery Systems Based on Different Targeting Mechanisms in the Targeted Therapy of Colorectal Cancer

Colorectal cancer (CRC) is a usual digestive tract malignancy and the third main cause of cancer death around the world, with a high occurrence rate and mortality rate. Conventional therapies for CRC have certain side effects and restrictions. However, the exciting thing is that with the rapid development of nanotechnology, nanoparticles have gradually become more valuable drug delivery systems than traditional therapies because of their capacity to control drug release and target CRC. This also promotes the application of nano-drug targeted delivery systems in the therapy of CRC. Moreover, to make nanoparticles have a better colon targeting effect, many approaches have been used, including nanoparticles targeting CRC and in response to environmental signals. In this review, we focus on various targeting mechanisms of CRC-targeted nanoparticles and their latest research progress in the last three years, hoping to give researchers some inspiration on the design of CRC-targeted nanoparticles.     

基于透明质酸的刺激响应纳米给药系统的研究进展

透明质酸(Hyaluronic acid, HA)是一种天然多糖,具有良好的生物相容性和生物降解性,利用 HA 构建的纳米载体自身就具有肿瘤靶向功能,可以作为抗癌药物载体将药物传递到肿瘤细胞内从而实现精准到达病患处。近年来透明质酸在应用于肿瘤靶向给药系统中的关注越来越多,成为了靶向治疗肿瘤的一大研究热点。基于透明质酸的基本特性和肿瘤靶向的生理学基础,在不同的刺激响应下,透明质酸型纳米给药系统能将药物集中释放于肿瘤的微环境内,更好地杀死肿瘤细胞,同时避免其他正常的组织受到药物损害。本文主要综述了透明质酸型纳米药物输送系统在各种刺激响应下释放药物的最新研究进展。     

Copolymers: efficient carriers for intelligent nanoparticulate drug targeting and gene therapy

Copolymers are among the most promising substances used in the preparation of drug/gene delivery systems. Different categories of copolymers, including block copolymers, graft copolymers, star copolymers and crosslinked copolymers, are of interest in drug delivery. A variety of nanostructures, including polymeric micelles, polymersomes and hydrogels, have been prepared from copolymers and tested successfully for their drug delivery potential. The most recent area of interest in this field is smart nanostructures, which benefit from the stimuli-responsive properties of copolymeric moieties to achieve novel targeted drug delivery systems. Different copolymer applications in drug/gene delivery using nanotechnology-based approaches with particular emphasis on smart nanoparticles are reviewed.     

Targeted Drug Delivery for the Treatment of Blood Cancers

Blood cancers are a type of liquid tumor which means cancer is present in the body fluid. Multiple myeloma, leukemia, and lymphoma are the three common types of blood cancers. Chemotherapy is the major therapy of blood cancers by systemic administration of anticancer agents into the blood. However, a high incidence of relapse often happens, due to the low efficiency of the anticancer agents that accumulate in the tumor site, and therefore lead to a low survival rate of patients. This indicates an urgent need for a targeted drug delivery system to improve the safety and efficacy of therapeutics for blood cancers. In this review, we describe the current targeting strategies for blood cancers and recently investigated and approved drug delivery system formulations for blood cancers. In addition, we also discuss current challenges in the application of drug delivery systems for treating blood cancers.     

Preparation and evaluation of physicochemical properties and anti-leishmanial activity of zirconium/tioxolone niosomes against Leishmania major

Due to the limitations of current chemotherapy for the treatment of leishmaniasis, there is an urgent requirement to search for new anti-leishmanial compounds and nano-drug delivery systems including niosomes. Therefore, the aim of this study was to prepare zirconium/tioxolone niosomes using the film hydration method and evaluate the physicochemical properties of the produced niosomes including morphology, size distribution, stability, and encapsulation efficiency. The best formulation was chosen as Span/Tween 40 (NZT₁) due to its physicochemical properties, and leishmanicidal activity against promastigotes and amastigotes was measured using both 3-(4,5-dimethylthiazol2yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry methods. In addition, to assess the mechanism of action of the prepared niosomes, apoptosis, levels of gene expression, reactive oxygen species (ROS) generation, superoxide dismutase (SOD) activity, and nitrite production were evaluated. The prepared formulation indicated log-normal particle size distribution curves, high encapsulation efficiency (more than 95.72 %), and good physical stability after one week, three months, and six months. Our findings demonstrated that amphotericin B was more effective than Zr/tioxolone niosomes (NZTs) due to the selectivity index (SI). However, the niosomal formulation of Zr/tioxolone showed no cytotoxic effect within the range of our experimental concentrations (CC₅₀ of 308.21 μg/mL). Moreover, the prepared niosomes increased the expression level of interleukin (IL)-12 and inducible nitric oxide synthase (iNOS) and significantly decreased the expression level of the IL-10 gene, which confirms the immunomodulatory role of NZTs. According to our findings in this study, the niosomal form of this combination can be considered for further therapeutic approaches against L. major in future planning.     

Pectin in controlled drug delivery – a review

Controlled drug delivery remains a research focus for public health to enhance patient compliance, drug efficiency and reduce the side effects of drugs. Pectin, an edible plant polysaccharide, has been shown to be useful for the construction of drug delivery systems for specific drug delivery. Several pectin derived formulations have been developed in our laboratory and tested in vitro, ex vivo, and in vivo for the ability to deliver bioactive substances for therapeutic purposes in the context of interactions with living tissues. Pectin derivatives carrying primary amine groups were more mucoadhesive and have shown potential in nasal drug delivery and other mucosal drug delivery. Pectin derivatives with highly esterified galacturonic acid residues are more hydrophobic and able to sustain the release of incorporated fragrances for a prolonged duration. Less esterified pectin derivatives are able to penetrate deeper into the skin and may be useful in aromatherapy formulations. Pectin, in combination with zein, a corn protein, forms hydrogel beads. The bound zein restricts bead swelling and retains the porosity of the beads; the pectin networks shield the zein from protease attack. The complex beads are ideal vehicles for colon-specific drug delivery. Studies presented in this paper indicate the flexibility and possibility to tailor pectin macromolecules into a variety of drug delivery systems to meet different clinical requirements. Mention of trade names or commercial products in this article is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the US Department of Agriculture.     

DNA纳米结构在药物转运载体和智能载药中的应用进展

纳米材料具有荷载效率高、靶向性能好、半衰期较长等优点, 非常适于作为药物转运载体, 可有效提高药物的水溶性、稳定性和疾病治疗效果.目前, 开发具有良好生物相容性、可控靶向释放能力和精确载药位点的理想药物转运载体, 仍是该领域存在的挑战性问题和当前研究的重点.自组装DNA纳米结构是一类具有精确结构、功能多样的纳米生物材料, 具有良好的生物相容性和稳定性、较高的膜渗透性和可控靶向释放能力等优点, 是理想的药物转运载体和智能载药材料.本文总结了DNA纳米结构的发展历程、DNA纳米结构作为药物转运载体的研究现状、动态DNA纳米结构在智能载药中的应用进展, 并对其发展前景进行了展望.     

Construction of Hyaluronic Acid-Covered Hierarchically Porous MIL-nanoMOF for Loading and Controlled Release of Doxorubicin

The porous nano-sized metal–organic framework (nanoMOF) and its proper surface modification could greatly promote the drug loading capability and introduce biocompatibility, biodegradability, and targeting functions into nano-drug delivery systems. Herein, the HACD@ADA-PA/MIL-101_NH₂ (Fe)-P nanoparticle was successfully fabricated through supramolecular and coordination interactions from three building blocks, including hierarchically porous MIL-101_NH₂ (Fe)-P nanoMOF, phosphite-modified adamantane (ADA-PA), and β-cyclodextrin (β-CD)-modified hyaluronic acid (HACD). The obtained HACD@ADA-PA/MIL-101_NH₂ (Fe)-P nanoparticle was nano-sized and highly stable in physiological fluids. The porous structure of HACD@ADA-PA/MIL-101_NH₂ (Fe)-P nanoparticle could effectively load the commercial chemotherapeutic drug doxorubicin (DOX) with an encapsulation rate of 41.20 % and a loading rate of 48.84 %. The obtained drug-loaded HACD@ADA-PA/MIL-101_NH₂ (Fe)-P@DOX nanoparticle was pH-sensitive and relatively stable at neutral condition (pH 7.2) but could release DOX in a controlled way in subacid solution at pH 5.7. The simulated in vitro DOX release experiment signified that the HACD@ADA-PA/MIL-101_NH₂ (Fe)-P@DOX nanoparticle could realize the controlled release of DOX in tumor issues.     

Cross‐Platform Comparison of Therapeutic Delivery from Multilamellar Lipid‐Coated Polymer Nanoparticles

Significant efforts have been invested in finding a delivery system that can encapsulate and deliver therapeutics. Core–shell polymer‐lipid hybrid nanoparticles have been studied as a promising platform because of their mechanical stability, narrow size distribution, biocompatibility, and ability to co‐deliver diverse drugs. Here, novel core–shell nanoparticles based on a poly(lactic‐co‐glycolic acid) (PLGA) core and multilamellar lipid shell are designed, where the lipid bilayers are crosslinked between the two adjacent bilayers (PLGA‐ICMVs). The cross‐platform performance of the nanoparticles to other polymer‐lipid hybrid platforms is examined, including physicochemical characteristics, ability to encapsulate a variety of therapeutics, biocompatibility, and functionality as a vaccine delivery platform. Differential abilities of nanoparticle systems to encapsulate distinct pharmaceutics are observed, which suggest careful consideration of the platform chosen depending on the therapeutic agent and desired function. The novel PLGA‐ICMV platform herein demonstrates great potential in stably encapsulating water‐soluble agents and therefore is an attractive platform for therapeutic delivery.     

Controlled drug delivery systems based on calixarenes

Recent advances on calixarene-based drug delivery systems in the form of inclusion complexes, amphiphilic self-assembly nanocarriers including micelles, hydrogels, vesicles and liposomes, and supramolecular nanovalves on mesoporous silicas, were reviewed and discussed.     

Plant-Based Colloidal Delivery Systems for Bioactives

The supplementation of plant-based foods and beverages with bioactive agents may be an important strategy for increasing human healthiness. Numerous kinds of colloidal delivery systems have been developed to encapsulate bioactives with the goal of improving their water dispersibility, chemical stability, and bioavailability. In this review, we focus on colloidal delivery systems assembled entirely from plant-based ingredients, such as lipids, proteins, polysaccharides, phospholipids, and surfactants isolated from botanical sources. In particular, the utilization of these ingredients to create plant-based nanoemulsions, nanoliposomes, nanoparticles, and microgels is covered. The utilization of these delivery systems to encapsulate, protect, and release various kinds of bioactives is highlighted, including oil-soluble vitamins (like vitamin D), ω-3 oils, carotenoids (vitamin A precursors), curcuminoids, and polyphenols. The functionality of these delivery systems can be tailored to specific applications by careful selection of ingredients and processing operations, as this enables the composition, size, shape, internal structure, surface chemistry, and electrical characteristics of the colloidal particles to be controlled. The plant-based delivery systems discussed in this article may be useful for introducing active ingredients into the next generation of plant-based foods, meat, seafood, milk, and egg analogs. Nevertheless, there is still a need to systematically compare the functional performance of different delivery systems for specific applications to establish the most appropriate one. In addition, there is a need to test their efficacy at delivering bioavailable forms of bioactives using in vivo studies.     

葡萄糖敏感苯硼酸基高分子纳米药物传输体系

近年来,智能葡萄糖敏感自调式药物传递系统备受关注。这种智能药物释放系统能够模拟胰腺分泌胰岛素的生理模式而精准调控药物释放并控制血糖水平,在糖尿病治疗中具有良好的应用前景。其中,苯硼酸(PBA)功能化的葡萄糖敏感高分子纳米载体成为近年来的研究热点之一。该类材料具有体系稳定、可长期储存、可逆的葡萄糖敏感性能等优势。根据响应因素不同,葡萄糖敏感药物传递系统可分为pH响应、温度响应和光响应等类型。本文重点介绍了基于PBA的葡萄糖敏感高分子纳米药物载体的发展过程、性能和应用,并对该领域的发展前景进行了展望。     

高分子包囊药物释放体系

用高分子作为载体的高分子微包囊和纳米级包囊药物制剂不仅能控制药物以一定的速度释放，而且可对生物体的生理指标变化作出反馈，因而可以成为靶向药物释放体系。通过用高分子包囊还可以延长蛋白质和多肽类药物的生理活性，提高药物稳定性，使之成为长效药物，并使一些难以口服的药物能够制成口服制剂。文章在介绍有关高分子药物释放体系的一些基本原理，以及与之相关的药学、药理学、物理化学和高分子材料科学方面知识的基础上，较全面地综述了高分子包囊药物的制备技术和应用。阐述了高分子包囊的粒径、表面积、孔度、药物性能和药含量，以及高分子包囊材料的性能对药物释放行为的影响。对药物传送机理亦进行了扼要的介绍。     

STING-activating drug delivery systems:Design strategies and biomedical applications

The stimulator of interferon genes(STING) shows promising clinical activity in infectious diseases and tumors.However,the lack of targeting capability and intracellular stability of STING agonists severely limits the therapeutic efficacy.Recently,drug delivery systems(DDSs) overcome these delivery barriers of STING agonists via passive or active cell targeting,prolonged blood circulation and drug release,and lysosome escape,etc.In this review,we will describe in detail how existing DDSs are designed to overcome delivery barriers and activate the STING pathway,and the current biomedical applications of STING-activating DDSs in the treatments of infectious diseases and tumors.Finally,the prospects and challenges of DDSs in STING activation are discussed.     

石墨烯纳米载药体系的制备及对人口腔鳞癌细胞杀伤效果

利用化学氧化还原法制备了氧化石墨烯,进一步超声破碎剥离,得到纳米氧化石墨烯,并对其进行聚乙二醇(PEG)的功能化修饰后载药顺铂。 采用扫描电子显微镜(SEM)、紫外-可见吸收光谱(UV-Vis)、傅立叶变换红外光谱(FTIR)对石墨烯纳米载药体系进行表征,细胞存活率实验(MTT)法检验石墨烯纳米载药体系对人口腔鳞癌(KB)细胞的杀伤作用。 结果表明,石墨烯纳米载药体系对顺铂的负载率为42.4%,聚乙二醇修饰后可以降低纳米氧化石墨烯的细胞毒性并提高生物相容性,对KB细胞具有双重的杀伤作用,为纳米氧化石墨烯在肿瘤治疗的临床应用提供了理论依据。     

Stereocomplex Polylactide for Drug Delivery and Biomedical Applications: A Review

Polylactide (PLA) is among the most common biodegradable polymers, with applications in various fields, such as renewable and biomedical industries. PLA features poly(D-lactic acid) (PDLA) and poly(L-lactic acid) (PLLA) enantiomers, which form stereocomplex crystals through racemic blending. PLA emerged as a promising material owing to its sustainable, eco-friendly, and fully biodegradable properties. Nevertheless, PLA still has a low applicability for drug delivery as a carrier and scaffold. Stereocomplex PLA (sc-PLA) exhibits substantially improved mechanical and physical strength compared to the homopolymer, overcoming these limitations. Recently, numerous studies have reported the use of sc-PLA as a drug carrier through encapsulation of various drugs, proteins, and secondary molecules by various processes including micelle formation, self-assembly, emulsion, and inkjet printing. However, concerns such as low loading capacity, weak stability of hydrophilic contents, and non-sustainable release behavior remain. This review focuses on various strategies to overcome the current challenges of sc-PLA in drug delivery systems and biomedical applications in three critical fields, namely anti-cancer therapy, tissue engineering, and anti-microbial activity. Furthermore, the excellent potential of sc-PLA as a next-generation polymeric material is discussed.     

Revitalizing Cytokine-Based Cancer Immunotherapy through Advanced Delivery Systems

Cytokines can coordinate robust immune responses, holding great promise as therapeutics against infections, autoimmune diseases, and cancers. In cancer treatment, numerous pro-inflammatory cytokines have displayed promising efficacy in preclinical studies. However, their clinical application is hindered by poor pharmacokinetics, significant toxicity and unsatisfactory anticancer efficacy. Thus, while IFN-α and IL-2 are approved for specific cancer treatments, other cytokines still remain subject of intense investigation. To accelerate the application of cytokines as cancer immunotherapeutics, strategies need to be directed to improve their safety and anticancer performance. In this regard, delivery systems could be used to generate innovative therapies by targeting the cytokines or nucleic acids, such as DNA and mRNA, encoding the cytokines to tumor tissues. This review centers on these innovative delivery strategies for cytokines, summarizing key approaches, such as gene delivery and protein delivery, and critically examining their potential and challenges for clinical translation.     

Application of Dendrimers in Anticancer Diagnostics and Therapy

The application of dendrimeric constructs in medical diagnostics and therapeutics is increasing. Dendrimers have attracted attention due to their compact, spherical three-dimensional structures with surfaces that can be modified by the attachment of various drugs, hydrophilic or hydrophobic groups, or reporter molecules. In the literature, many modified dendrimer systems with various applications have been reported, including drug and gene delivery systems, biosensors, bioimaging contrast agents, tissue engineering, and therapeutic agents. Dendrimers are used for the delivery of macromolecules, miRNAs, siRNAs, and many other various biomedical applications, and they are ideal carriers for bioactive molecules. In addition, the conjugation of dendrimers with antibodies, proteins, and peptides allows for the design of vaccines with highly specific and predictable properties, and the role of dendrimers as carrier systems for vaccine antigens is increasing. In this work, we will focus on a review of the use of dendrimers in cancer diagnostics and therapy. Dendrimer-based nanosystems for drug delivery are commonly based on polyamidoamine dendrimers (PAMAM) that can be modified with drugs and contrast agents. Moreover, dendrimers can be successfully used as conjugates that deliver several substances simultaneously. The potential to develop dendrimers with multifunctional abilities has served as an impetus for the design of new molecular platforms for medical diagnostics and therapeutics.