Advances in Research on Cellulose-based Drug Carriers

Traditional drug delivery methods are prone to large fluctuations in drug concentration and require multiple frequent doses.As a green material with excellent properties,cellulose has been widely used as a drug carrier for the development and preparation of drug controlled-release system.Based on the mechanisms of slow drug release,such as dissolution-diffusion release,degradation release,and nanochannel-controlled release,the preparation methods of cellulose-based drug carriers are introduced in this paper.The applications of cellulose-based drug carriers in the fields of antitumor therapy,antibacterial therapy,chronic disease treatment,and viral disease treatment are summarized with the aim of providing a useful reference for research on cellulose-based drug carriers.

Superparticles Formed by Amphiphilic Tadpole-like Single Chain Polymeric Nanoparticles and Their Application as an Ultrasonic Responsive Drug Carrier

Herein, we report self-assembly of tadpole-like single chain polymeric nanoparticles （TPPs） and the ultrasonic response of the resultant superparticles. The TPPs are with an intramolecularly crosslinked poly（2-（methacryloyloxy）ethyl pent-4-ynoate）-rpoly（hydroxyethyl methacrylate） （PMAEP-r-PHEMA） chain as the ＂head＂ and a poly（2- （dimethylamino）ethyl methacrylate （PDMAEMA） linear chain as the ＂tail＂, and are pre- pared simply and emciently by Glaser-coupling of the pendant alkynes in the PMAEP-r- PHEMA block in the common solvent methanol. The formation of the TPPs was confirmed by gel permeation chromatograph, nuclear magnetic resonance spectroscopy, dynamic light scattering, static dynamic scattering, and transmission electron microscopy. In aqueous solution, the amphiphilic TPPs could self-assemble into regular superparticles, driven by aggregation of the hydrophobic ＂heads＂. Since in the structure there is no chain entanglement and the embedding of PDMAEMA chains disturb close-packing of the ＂heads＂, the superpartieles are responsive to a low-energy ultrasonic vibration, as evidenced by greatly enhanced release of the functional molecules from the superparticles by treatment of a low-energy ultrasound. Therefore, the superparticles should be very promising in the use as the drug carriers that can be manipulated from a long distance, considering that ultrasonic energy can be focused at a small area in a relatively long distance from the ultrasound-radiating source.

Dendritic macromolecules as nano-scale drug carriers:Phase solubility,in vitro drug release,hemolysis and cytotoxicity study

Potential of nanoscale triazine based dendritic macromolecules G1,G2 and G3 as solubility enhancers of drug was investigated.Effect of pH,concentration and generation of synthesized dendritic macromolecules on solubility of ketoprofen was studied.G3 dendrimer was further exploited as carrier for sustained release.Ketoprofen was encapsulated by inclusion complex method and also characterized by Flourier Transform Infrared spectroscopy.Sustained release study of ketoprofen from ketoprofen loaded dendrimer was carried out and compared with free ketoprofen.Hemolytic potential and Cytotoxicity assay using A-549 lung cancer cell lines revealed that synthesized triazine based dendritic macromolecules having more potential that commercially available PAMAM dendrimer.

Size,shape,charge and“stealthy”surface:Carrier properties affect the drug circulation time in vivo

The present review sets out to discuss recent developments of the effects and mechanisms of carrier properties on their circulation time.For most drugs,sufficient in vivo circulation time is the basis of high bioavailability.Drug carrier plays an irreplaceable role in helping drug avoid being quickly recognized and cleared by mononuclear phagocyte system,to give drug enough time to arrive at targeted organ and tissue to play its therapeutic effect.The physical and chemical properties of drug carriers,such as size,shape,surface charge and surface modification,would affect their in vivo circulation time,metabolic behavior and biodistribution.The final circulation time of carriers is determined by the balance between macrophage recognitions,blood vessel penetration and urine excretion.Therefore,when designing the drug delivery system,we should pay much attention to the properties of drug carriers to get enough in vivo circulation time to arrive at target site eventually.This article mainly reviews the effect of carrier size,size,surface charge and surface properties on its circulation time in vivo,and discusses the mechanism of these properties affecting circulation time.This review has reference significance for the research of long-circulation drug delivery system.

Novel drug delivery systems for inflammatory bowel disease

Inflammatory bowel disease(IBD)is a chronic illness characterized by relapsing inflammation of the intestines.The disorder is stratified according to the severity and is marked by its two main phenotypical representations:Ulcerative colitis and Crohn’s disease.Pathogenesis of the disease is ambiguous and is expected to have interactivity between genetic disposition,environmental factors such as bacterial agents,and dysregulated immune response.Treatment for IBD aims to reduce symptom extent and severity and halt disease progression.The mainstay drugs have been 5-aminosalicylates(5-ASAs),corticosteroids,and immunosuppressive agents.Parenteral,oral and rectal routes are the conventional methods of drug delivery,and among all,oral administration is most widely adopted.However,problems of systematic drug reactions and low specificity in delivering drugs to the inflamed sites have emerged with these regular routes of delivery.Novel drug delivery systems have been introduced to overcome several therapeutic obstacles and for localized drug delivery to target tissues.Enteric-coated microneedle pills,various nano-drug delivery techniques,prodrug systems,lipid-based vesicular systems,hybrid drug delivery systems,and biologic drug delivery systems constitute some of these novel methods.Microneedles are painless,they dislodge their content at the affected site,and their release can be prolonged.Recombinant bacteria such as genetically engineered Lactococcus Lactis and eukaryotic cells,including GM immune cells and red blood cells as nanoparticle carriers,can be plausible delivery methods when evaluating biologic systems.Nano-particle drug delivery systems consisting of various techniques are also employed as nanoparticles can penetrate through inflamed regions and adhere to the thick mucus of the diseased site.Prodrug systems such as 5-ASAs formulations or their derivatives are effective in reducing colonic damage.Liposomes can be modified with both hydrophilic and lipophilic particles and act as lipid-based vesicular systems,while hybrid drug delivery systems containing an internal nanoparticle section for loading drugs are potential routes too.Leukosomes are also considered as possible carrier systems,and results from mouse models have revealed that they control anti-and pro-inflammatory molecules.

Research progress in nanoparticles as anticancer drug carrier

Nanoparticles drug delivery system has sustained and controlled release features as well as targeted drug delivery, which can change the characteristics of drug distribution in vivo. It can increase the stability of the drug and enhance drug bioavailability. The selective targeting of nanoparticles can be achieved through enhanced permeability and retention effect and a conjugated specific ligand or through the effects of physiological conditions, such as pH and temperature. Nanoparticles can be prepared by using a wide range of materials and can be used to encapsulate chemotherapeutic agents to reduce toxicity, which can be used for imaging, therapy, and diagnosis. In this research, recent progress on nanoparticles as a targeted drug delivery system will be reviewed, including positive-targeting, negative-targeting, and physicochemical-targeting used as anticancer drug carriers.

Preparation and Drug-release Behavior of β-TCP Ceramics Drug Carrier in vitro

β-TCP ceramics drug carrier was first prepared and characterized. SEM showed that β-TCP carrier was in porous amorphous structure with diameters around 10 μm. The physical properties including apparent porosity, volume-weight, tensile strength and the permeability were measured and the results indicated those properties fit the clinical usage of β-TCP drug carrier. Furthermore, drug release experiment in vitro showed that the carrier could prolong drug release in simulated body fluid which provides basis for the clinical use of β-TCP ceramics as drug carrier.

The application of open disk-like structures as model membrane and drug carriers

The objective of this review is to outline the application of bicelles(or called bilayer micelles)and bilayer nanodisks in pharmaceutics,pharmaceutical analysis and biochemistry.The application of open disk-like structures as model membrane and drug carrier has been described.The exploration of many reports in different fields suggested that these open disk-like structures have great potential in studying interactions between drug-membrane and structure/function studies of membrane-bound proteins.Furthermore,they could be applied as promising carriers for in vivo delivery of drugs,protein and peptide.

Research progress on pharmacological action and effective drug carrier of berberine

Berberine(BBR)is an isoquinoline alkaloid that can be extracted from the traditional Chinese medicine Huang Lian.It has anti-inflammatory,anti-cancer,protection of nerves,hypoglycemic,blood lipid,anti-oxidation,antibacterial and other effects.It can be used clinically to treat chronic colitis,bacterial vaginitis,rheumatoid arthritis,breast cancer,liver cancer,Alzheimer's disease,diabetes,obesity and other common diseases.This paper reviews the pharmacological effects of berberine and the research progress of effective drug carriers in order to provide new ideas for the clinical application of berberine.

Betamethasone Dipropionate Loaded in Nanoliposomes vs Conventional Betamethasone Dipropionate: Comparative Study of Permeability and Penetrability in Vitro and ex Vivo

A betamethasone dipropionate (BD) liposomal cream was developed to treat rheumatological, inflammatory, allergic diseases and psoriasis. BD is a corticosteroid, anti-inflammatory, and immunosuppressant. However, adverse effects are associated with prolonged topical use. For this reason, liposomes were loaded with BD because they offer excellent biocompatibility, bio adhesiveness, and penetrability that improve the effects caused by the conventional drug. Liposomal dispersions were prepared by emulsification using phospholipid 90 (lipid) and Tween 80 (surfactant). The particle size, polydispersity index (PDI), and zeta potential were measured using a particle analyzer. The betamethasone (BM) percentage of encapsulated active (EA) ingredient was also determined through High Performance Liquid Chromatography (HPLC). The Franz cell and tape stripping characterized these in vitro and ex vivo. Then the final formulation reached a particle size of 70.80 ± 3.31 nm, a PDI of 0.242 ± 0.038, a zeta potential of −11.68 ± 0.77 mv and encapsulate active of 83.1% ± 2.4, complying with the parameters of a nanotechnological formulation. In vitro and ex vivo studies confirmed significantly efficacy of the cream over the commercial product, through the greater penetration into the pig ear skin, resulting in an improved drug. Finally, the liposomal cream demonstrated significant potential for enhanced percutaneous absorption, attributed to its nanometric size. This innovative nanotechnology approach aims to reduce the frequency of topical applications, thereby minimizing the side effects associated with psoriasis treatment.

静电纺丝构建中药控释系统的研究及应用

背景:静电纺丝多孔纳米纤维是一种具有优良性能和可设计性的材料,将传统中药与其联合构建新型中药控释系统是实现中药的控制释放和提高生物利用度的有效途径,具有广阔应用前景。目的:综述静电纺丝中药控释系统的构建方法及其在医学领域相关研究进展。方法:以“静电纺丝,中药,药物载体,释药系统,组织工程,敷料”为中文检索词,以“electrospinning,traditional Chinese medicine,drug carrier,drug delivery system,tissue engineering,dressing”为英文检索词,检索中国知网、PubMed和Web of Science数据库的关于静电纺丝中药控释系统的研究应用文献,检索时间范围为2013-2023年,最终纳入62篇文献进行综述分析。结果与结论:①构建电纺多孔纤维中药控释系统的关键要素为基质材料、中药成分和载药方式。②电纺多孔纤维中药控释系统的构建可依据应用场景和治疗目的进行,首先选定中药成分种类,然后依据药物特性选择与其适配的聚合物基体及溶液,最后依据释药需求设计纤维结构并采用适宜的载药方式。③目前在电纺纤维中药控释系统中所应用的药剂以易制备纺丝溶液的植物中药提取物为主,缺少动物中药和矿物中药的系统研究。④共混载药是研究应用最多的载药方式,且通过对溶液理化性质的优化和负载物质多样性的选择不断扩展其释药特性和适应场景;同轴、多轴及顺序纺丝等载药方式可以制备具有多层成分性质不同的复合纤维,具有广阔发展前景。⑤电纺纤维中药控释系统早期应用集中于医用敷料方面,利用中药活性成分的抗菌止血功能,近年来发现中药某些成分能促进细胞黏附增殖分化,开启了组织工程领域的探索研究。⑥目前对电纺多孔纤维中药控释系统的研究主要集中在对负载材料、工艺、理化性能、生物性能的表征和优化上,而对机制的研究较少,其在临床中的应用尚未普及,在体内的不良反应尚不明了,对其降解行为与释药行为的相互影响也缺乏研究。⑦未来研究中需要考虑:通过改善中药与纺丝溶剂的理化性能和加大中药活性成分的提纯以扩大非植物中药的应用范围,对中药成分的治疗效果和作用机制进行全面研究,并阐明控释系统的降解行为与释药行为的相互影响规律,在更准确的机制下实现中药与电纺纳米纤维更完美的联合和应用。

刺激响应型纳米载体的设计和研究进展

刺激响应型纳米载体主要包括内源性、外源性、双重和多重刺激响应型纳米载体等。内源性刺激响应型纳米载体的设计主要基于肿瘤组织和健康组织之间存在的一些内在生理学显著差异;外源性刺激响应型纳米载体的设计,通常会采用远程装置,具有靶点特异性和药物时-空可控释放的优点;双重和多重刺激响应型纳米载体与单刺激响应型纳米载体相比,具有多功能协同功效的优点。本文主要综述了内源性、外源性、双重和多重刺激响应型纳米载体的设计和研究进展,并对其在肿瘤治疗中的应用前景进行了展望。

Nanoparticles for the treatment of spinal cord injury

Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a slow process, partly due to the difficulty of delivering drugs effectively. Nanoparticles, with their targeted delivery capabilities, biocompatibility, and enhanced bioavailability over conventional drugs, are garnering attention for spinal cord injury treatment. This review explores the current mechanisms and shortcomings of existing treatments, highlighting the benefits and progress of nanoparticle-based approaches. We detail nanoparticle delivery methods for spinal cord injury, including local and intravenous injections, oral delivery, and biomaterial-assisted implantation, alongside strategies such as drug loading and surface modification. The discussion extends to how nanoparticles aid in reducing oxidative stress, dampening inflammation, fostering neural regeneration, and promoting angiogenesis. We summarize the use of various types of nanoparticles for treating spinal cord injuries, including metallic, polymeric, protein-based, inorganic non-metallic, and lipid nanoparticles. We also discuss the challenges faced, such as biosafety, effectiveness in humans, precise dosage control, standardization of production and characterization, immune responses, and targeted delivery in vivo. Additionally, we explore future directions, such as improving biosafety, standardizing manufacturing and characterization processes, and advancing human trials. Nanoparticles have shown considerable progress in targeted delivery and enhancing treatment efficacy for spinal cord injuries, presenting significant potential for clinical use and drug development.

Mesenchymal stem cell-derived exosomes as a new drug carrier for the treatment of spinal cord injury:A review

Spinal cord injury(SCI)is a devastating traumatic disease seriously impairing the quality of life in patients.Expectations to allow the hopeless central nervous system to repair itself after injury are unfeasible.Developing new approaches to regenerate the central nervous system is still the priority.Exosomes derived from mesenchymal stem cells(MSC-Exo)have been proven to robustly quench the inflammatory response or oxidative stress and curb neuronal apoptosis and autophagy following SCI,which are the key processes to rescue damaged spinal cord neurons and restore their functions.Nonetheless,MSC-Exo in SCI received scant attention.In this review,we reviewed our previous work and other studies to summarize the roles of MSC-Exo in SCI and its underlying mechanisms.Furthermore,we also focus on the application of exosomes as drug carrier in SCI.In particular,it combs the advantages of exosomes as a drug carrier for SCI,imaging advantages,drug types,loading methods,etc.,which provides the latest progress for exosomes in the treatment of SCI,especially drug carrier.

甘草酸、姜黄素和羟基喜树碱自组装纳米粒递药系统的工艺优化研究

目的:以两亲性药物分子甘草酸(GA)、疏水性药物姜黄素(CUR)和羟基喜树碱(HCPT)为材料,通过自组装形式构建GA、CUR和HCPT纳米粒递药系统(GA/CUR/HCPT-NPs),考察其制备工艺并进行质量评价。方法:采用反溶剂沉淀法和透析法相结合制备GA/CUR/HCPT-NPs,利用响应面Box-Behnken法对制备工艺进行优化,最终获得尺寸合适,稳定电荷,高载药量的GA/CUR/HCPT-NPs;并对优化出来的GA/CUR/HCPT-NPs进行核磁共振氢谱(1HNMR)、差示扫描量热法(DSC)、高分辨X射线衍射法(XRD)、傅里叶红外分光光度法(FTIR)、紫外分光光度法(UV)等表征和微观形态观察,并测定GA/CUR/HCPT-NPs中GA、CUR和HCPT含量大小。结果:得到的最优处方为去离子水体积30 mL,二甲基亚砜(DMSO)1 min内滴入去离子水,制备温度为40℃,确定GA、CUR、HCPT投药量分别为6.00 mg、10.03 mg、5.01 mg;测量GA/CUR/HCPT-NPs粒径为(146.37±0.15)nm,且带较高的稳定电荷-(34.43±0.77)mV,PDI为0.157±0.01,透射电子显微镜(TEM)和扫描电子显微镜(SEM)可观察到GA/CUR/HCPT-NPs是类球形或球形,并且均匀分布;1HNMR、DSC、XRD等证明了成功自组装成稳定的GA/CUR/HCPT-NPs,并且在7 d内4℃保存条件下稳定性良好;高效液相色谱(HPLC)测定GA/CUR/HCPT-NPs中GA、CUR、HCPT的载药量分别为57.19%、39.17%和3.07%。结论:本研究通过优化的反溶剂沉淀法结合透析法成功制备尺寸合适、均匀分布的GA/CUR/HCPT-NPs,为进一步实验奠定了基础。

血小板药物递送系统的研究进展

药物递送系统对于各类疾病意义非凡,但传统药物载体面临细胞毒性强、组织相容性低、半衰期短和靶向性弱等诸多挑战。血小板及其相关衍生物作为新型药物载体具有更为显著的优势。由于血小板自身的生理特点,以及在肿瘤、心血管疾病、血栓性疾病、感染等多种疾病中发挥的病理生理作用,血小板能够弥补传统药物载体的缺陷,具有极大的临床转化意义。该文总结了血小板相关药物递送系统目前的研究进展,以期为新型药物载体研究提供参考。

Hydrogel-based local drug delivery strategies for spinal cord repair

Spinal cord injury results in significant loss of motor, sensory, and autonomic functions. Although a wide range of therapeutic agents have been shown to attenuate secondary injury or promote regeneration/repair in animal models of spinal cord injury, clinical translation of these strategies has been limited, in part due to difficulty in safely and effectively achieving therapeutic concentrations in the injured spinal cord tissue. Hydrogelbased drug delivery systems offer unique opportunities to locally deliver drugs to the injured spinal cord with sufficient dose and duration, while avoiding deleterious side effects associated with systemic drug administration. Such local drug delivery systems can be readily fabricated from biocompatible and biodegradable materials. In this review, hydrogel-based strategies for local drug delivery to the injured spinal cord are extensively reviewed, and recommendations are made for implementation.

Functionalized magnetic nanoparticles for drug delivery in tumor therapy

The side effects of chemotherapy are mainly the poor control of drug release. Magnetic nanoparticles(MNPs) have super-paramagnetic behaviors which are preferred for biomedical applications such as in targeted drug delivery, besides, in magnetic recording, catalysis, and others. MNPs, due to high magnetization response, can be manipulated by the external magnetic fields to penetrate directly into the tumor, thus they can act as ideal drug carriers. MNPs also play a crucial role in drug delivery system because of their high surface-to-volume ratio and porosity. The drug delivery in tumor therapy is related to the sizes, shapes, and surface coatings of MNPs as carriers. Therefore, in this review, we first summarize the effects of the sizes, shapes, and surface coatings of MNPs on drug delivery, then discuss three types of drug release systems, i.e., p H-controlled, temperature-controlled, and magnetic-controlled drug release systems, and finally compare the principle of passive drug release with that of active drug release in tumor therapy.

Advances in studies of phospholipids as carriers in skin topical application

Objective： This article provides an overview of characteristics of phospholipids, the characteristics and influential factors of liposome and microemulsion as carriers for skin delivery of drugs, and the latest advances of the phospholipids carriers in transdermal delivery systems. The perspective is that phospholipids carriers may be capable of a wide range of applications in the transdermal delivery system.

Drug Release Characteristics of Hydroxyapatite Bone Cement

To discuss the feasibility of bydroxyapatite bone cement （HAC） used as a drug delivery carrier and observe the bacteriostatic activity of HAC/ Norvancomycin（ HAC/ NVCM ） composite in vitro and its release characteristics in vivo. Bacteriostatic zone and cycle of composite containing 1.5wt% of NVCM were measured in vitro studies. In vivo stndies , the composite was implanted into the top of rabbit＇ s tibia as the local medication group, HAC without NVCM being composed was also implanted and NVCM was injected into auricular vein as the systemic medication group. Cnncentrations of NVCM in blood and local bone were measured in both groups at different time points. The experimental results showed that HAC did not influence the bacteriostatic activity of NVCM otviously, and NVCM exist in the porosities of HAC in the pattern of amorphism. The blood coueemrations of NVCM in local medication group were always lower than those in systemic medication group at any time point, while the bone concentrations of NVCM in local medication group were much higher than those of systemic medication group,which remained to be 3.96μg/mg/mL after 2 weeks. And HAC has good release characteristics as a drug delivery earricr.