生物可降解聚合物纳米粒给药载体

生物可降解聚合物纳米粒用于给药载体具有广阔的前景。本文综述了生物可降解聚合物纳米粒给药载体领域的最新进展 :包括纳米粒表面修饰特性、药物释放、载多肽和蛋白质等生物大分子药物传输中的潜在应用。     

综述——纳米材料与药物输递：聚乙二醇/聚己内酯嵌段共聚物温敏水凝胶及其在局部药物递送中的应用

近年来,温敏水凝胶被广泛用于药物递送、组织工程等生物医用领域．其中,由聚乙二醇与脂肪族可降解聚酯合成的两亲性聚合物的自组装胶束形成的温敏水凝胶是一种重要的温敏凝胶材料．本文针对聚乙二醇(PEG)与聚己内酯(PCL)形成的两亲性嵌段聚合物温敏水凝胶体系,综述了聚合物分子质量、嵌段序列结构,亲疏水段分子质量与比例、疏水段化学结构等因素对温敏行为的影响,以及该温敏水凝胶在局部药物递送方面的研究进展．     

聚乙二醇-聚乳酸嵌段共聚物在药物递送系统中的应用

聚乙二醇-聚乳酸嵌段共聚物具备良好的生物相容性和生物可降解性,是良好的纳米级药物载体。嵌段共聚物具有载药能力强、粒径小、体内循环时间长、主动靶向性和被动靶向性等特点,因此在药物递送系统中得到广泛应用。简要介绍了聚乙二醇-聚乳酸嵌段共聚物的合成和性质,及其作为脂质体、胶束、微球等载体在药物递送系统中的最新进展。     

三嵌段聚合物在药物制剂中的应用研究进展

三嵌段聚合物系由2 种或2 种以上不同化合物通过聚合反应而合成的一种新型多功能两亲性载体材料,在水溶液中呈现优良的自组装性能。其用作药物载体时,可依据需求,通过改变其组成和结构而使其拥有温度敏感、pH 敏感、磁敏感等多种特性,将其制成适宜剂型,能达到改善药物的溶解性等理化性质以及靶向性、缓控释性和生物利用度的目的,其在药物制剂领域具有广阔的应用前景。简介各种类型的三嵌段聚合物,着重概述近年来三嵌段聚合物在不同制剂剂型中的应用研究。     

混合胶束作为药物载体的研究进展

许多抗肿瘤药物因为水溶解性差,在临床上的应用受到了很大影响。胶束可将药物包载到疏水核,可显著提高药物的水溶解性,是一种极具潜力的新型给药体系。然而胶束也面临着一系列问题,比如说需要提高其在体内的动力学稳定性和热力学稳定性等。与此同时,如果想要在单一的胶束体系上实现多种功能,需要对载体材料进行繁杂的修饰,也是一个难题。由不同嵌段聚合物、聚合物/表面活性剂自组装成的混合胶束或聚离子复合物胶束,相对于单一嵌段聚合物形成的胶束而言,物理稳定性和载药能力都得到了提高。同时,通过将具有不同官能团的聚合物制备成混合胶束,可以直接方便得到多功能复合的体系。本文对混合胶束载体系统的药剂学进展进行了综述。     

生物可降解聚乙二醇-嵌段-聚乳酸的协同给药研究

肿瘤单一药物治疗的效果往往不佳,且易产生耐药性,因此,肿瘤的多药协同治疗具有明显优势,并逐渐引起重视。本工作基于具有良好生物相容性和生物可降解性的聚乙二醇-嵌段-聚乳酸(PEG-b-PLA)两嵌段聚合物,物理包埋两种化疗药物,阿霉素(Doxorubicin,DOX)和喜树碱(Camptothecin,CPT),实现两种化疗药物的共传输、药物释放与协同给药,表现出良好的抗肿瘤活性。     

高分子囊泡在药物释放体系的应用

高分子囊泡作为一种新型的纳米药物载体,具有生物可降解性、稳定性、生物相容性及可修饰的多功能化等特点。改变聚合物种类和亲水-疏水嵌段的比例,可以制备具有不同形态和膜特性的高分子囊泡。经过修饰后的高分子囊泡,可赋予其更多的功能,从而实现药物的控释和药物靶向的能力。对高分子囊泡的结构、组成和制备方法以及在药物释放体系的应用等方面进行了较为详细的综述,目的是了解高分子囊泡最新研究进展以及未来科学家们亟须解决的重要问题。     

合成生物学技术在聚羟基脂肪酸酯PHA生产中的应用

合成生物学的迅猛发展使其在各个领域得到了广泛应用,底盘设计、元件组装、代谢网络的从头构建、大片段DNA克隆、多片段DNA拼接等合成生物学技术的开发和利用大大提高了工业生物技术的竞争力.聚羟基脂肪酸酯(PHA)是一种具有生物可降解和生物相容性等优良特性的生物塑料,可以在许多细菌胞内合成,已经被开发应用于多个领域.但是,PHA高昂的生产成本阻碍了其大规模应用.基于合成生物学研究而得到的新方法、新技术可以改变细菌生长模式、生长条件以及细菌形态,从而进一步降低PHA的生产成本.另一方面,通过改造细菌基因组如弱化?-氧化途径可以得到不同种类的重组菌株,用于生产具有不同性能的包括无规共聚物、嵌段共聚物、带有官能团的聚合物等在内的新型多功能PHA材料.合成生物学的应用开创了低成本、高附加值的PHA材料生产的新时代,为PHA的产业化奠定了坚实的基础.     

脂质纳米粒子在药物中的应用

脂质纳米粒子是用生物可降解的脂质制备,故这种载体系统拥有很好的生物相容性和安全性。本文着重介绍脂质纳米粒子在药物中的应用,如抗肿瘤药物、抗病毒药物、抗炎症药物、免疫药物、抗真菌药物、降血糖药物等。最后,指出了脂质纳米粒子的发展前景。     

生物可降解塑料在不同环境条件下的降解研究进展北大核心CSCD

当前社会塑料制品的使用需求持续增加,塑料垃圾处理压力不断增大,减缓塑料污染成为当务之急,生物可降解塑料因可在一定生物活性环境下较快降解而备受关注,具有广阔的应用前景。生物可降解塑料降解条件复杂,影响因素众多,对不同生物可降解塑料降解规律,降解微生物和功能酶的透彻掌握,是实现其全面利用和高效资源化处理处置的基础和前提。文章系统梳理了常见生物可降解塑料的种类、性能、优缺点和主要用途,全面综述了生物可降解塑料的降解机理、降解微生物和功能酶,以及生物可降解塑料在不同环境条件下的降解周期和程度,以期为生物可降解塑料的微生物降解研究提供借鉴,为生物可降解塑料废弃物的高效处理处置和彻底降解提供科学参考。     

A Review of Multi-Responsive Membranous Systems for Rate-Modulated Drug Delivery

Membrane technology is broadly applied in the medical field. The ability of membranous systems to effectively control the movement of chemical entities is pivotal to their significant potential for use in both drug delivery and surgical/medical applications. An alteration in the physical properties of a polymer in response to a change in environmental conditions is a behavior that can be utilized to prepare ‘smart’ drug delivery systems. Stimuli-responsive or ‘smart’ polymers are polymers that upon exposure to small changes in the environment undergo rapid changes in their microstructure. A stimulus, such as a change in pH or temperature, thus serves as a trigger for the release of drug from membranous drug delivery systems that are formulated from stimuli-responsive polymers. This article has sought to review the use of stimuli-responsive polymers that have found application in membranous drug delivery systems. Polymers responsive to pH and temperature have been extensively addressed in this review since they are considered the most important stimuli that may be exploited for use in drug delivery, and biomedical applications such as in tissue engineering. In addition, dual-responsive and glucose-responsive membranes have been also addressed as membranes responsive to diverse stimuli.     

Polyrotaxanes for applications in life science and biotechnology

Due to their low cytotoxicity, controllable size, and unique architecture, cyclodextrin (CD)-based polyrotaxanes and polypseudorotaxanes have inspired interesting exploitation as novel biomaterials. This review will update the recent progress in the studies on the structures of polyrotaxanes and polypseudorotaxanes based on different CDs and polymers, followed by summarizing their potential applications in life science and biotechnology, such as drug delivery, gene delivery, and tissue engineering. CD-based biodegradable polypseudorotaxane hydrogels could be used as promising injectable drug delivery systems for sustained and controlled drug release. Polyrotaxanes with drug or ligand-conjugated CDs threaded on polymer chain with biodegradable end group could be useful for controlled and multivalent targeting delivery. Cationic polyrotaxanes consisting of multiple oligoethylenimine-grafted CDs threaded on a block copolymer chain were attractive non-viral gene carries due to the strong DNA-binding ability, low cytotoxicity, and high gene transfection efficiency. Cytocleavable end caps were also introduced in the polyrotaxane systems in order to ensure efficient endosomal escape for intracellular trafficking of DNA. Finally, hydrolyzable polyrotaxane hydrogels with cross-linked α-CDs could be a desirable scaffold for cartilage and bone tissue engineering.     

Drug delivery systems: polymers and drugs monitored by capillary electromigration methods

In this paper, different electromigration methods used to monitor drugs and polymers released from drug delivery systems are reviewed. First, an introduction to the most typical arrangements used as drug delivery systems (e.g., polymer-drug covalent conjugates, membrane or matrix-based devices) is presented. Next, the principles of different capillary electromigration procedures are discussed, followed by a revision on the different procedures employed to monitor the release of drugs and the degradation or solubilization of the polymeric matrices from drug delivery systems during both in vitro and in vivo assays. A critical comparison between these capillary electrophoretic methods and the more common chromatographic methods employed to analyze drugs and polymers from drug delivery systems is presented. Finally, future outlooks of these electromigration procedures in the controlled release field are discussed.     

Fluidized or not fluidized? Biophysical characterization of biohybrid lipid/protein/polymer liposomes and their interaction with tetracaine

BackgroundNanomedicine and the pharmaceutical industry demand the investigation of new biomaterials to improve drug therapies. Combinations of lipids, proteins, and polymers represent innovative platforms for drug delivery. However, little is known about the interactions between such compounds and this knowledge is key to prepare successful drug delivery systems.MethodsBiophysical properties of biohybrid vesicles (BhVs) composed of phospholipids, proteins, and amphiphilic block copolymers, assembled without using organic solvents, were investigated by differential scanning calorimetry and dynamic light scattering. We studied four biohybrid systems; two of them included the effect of incorporating tetracaine. Thermal changes of phospholipids and proteins when interacting with the amphiphilic block copolymers and tetracaine were analyzed.ResultsLysozyme and the copolymers adsorb onto the lipid bilayer modifying the phase transition temperature, enthalpy change, and cooperativity. Dynamic light scattering investigations revealed relevant changes in the size and zeta potential of the BhVs. Interestingly, tetracaine, a membrane-active drug, can fluidize or rigidize BhVs.ConclusionsWe conclude that positively charged regions of lysozyme are necessary to incorporate the block copolymer chains into the lipid membrane, turning the bilayer into a more rigid system. Electrostatic properties and the hydrophilic-lipophilic balance are determinant for the stability of biohybrid membranes.General significanceThis investigation provides fundamental information associated with the performance of biohybrid drug delivery systems and can be of practical significance for designing more efficient drug nanocarriers.     

Enhanced stability of polymeric micelles based on postfunctionalized poly(ethylene glycol)-b-poly(γ-propargyl L-glutamate): the substituent effect

One of the major obstacles that delay the clinical translation of polymeric micelle drug delivery systems is whether these self-assembled micelles can retain their integrity in blood following intravenous (IV) injection. The objective of this study was to evaluate the impact of core functionalization on the thermodynamic and kinetic stability of polymeric micelles. The combination of ring-opening polymerization of N-carboxyanhydride (NCA) with highly efficient "click" coupling has enabled easy and quick access to a family of poly(ethylene glycol)-block-poly(γ-R-glutamate)s with exactly the same block lengths, for which the substituent "R" is tuned. The structures of these copolymers were carefully characterized by (1)H NMR, FT-IR, and GPC. When pyrene is used as the fluorescence probe, the critical micelle concentrations (CMCs) of these polymers were found to be in the range of 10(-7)-10(-6) M, which indicates good thermodynamic stability for the self-assembled micelles. The incorporation of polar side groups in the micelle core leads to high CMC values; however, micelles prepared from these copolymers are kinetically more stable in the presence of serum and upon SDS disturbance. It was also observed that these polymers could effectively encapsulate paclitaxel (PTX) as a model anticancer drug, and the micelles possessing better kinetic stability showed better suppression of the initial "burst" release and exhibited more sustained release of PTX. These PTX-loaded micelles exerted comparable cytotoxicity against HeLa cells as the clinically approved Cremophor PTX formulation, while the block copolymers showed much lower toxicity compared to the cremophor-ethanol mixture. The present work demonstrated that the PEG-b-PPLG can be a uniform block copolymer platform toward development of polymeric micelle delivery systems for different drugs through the facile modification of the PPLG block.     

Beyond traditional therapy: Mucoadhesive polymers as a new frontier in oral cancer management

In recent times mucoadhesive drug delivery systems are gaining popularity in oral cancer. It is a malignancy with high global prevalence. Despite significant advances in cancer therapeutics, improving the prognosis of late-stage oral cancer remains challenging. Targeted therapy using mucoadhesive polymers can improve oral cancer patients' overall outcome by offering enhanced oral mucosa bioavailability, better drug distribution and tissue targeting, and minimizing systemic side effects. Mucoadhesive polymers can also be delivered via different formulations such as tablets, films, patches, gels, and nanoparticles. These polymers can deliver an array of medicines, making them an adaptable drug delivery approach. Drug delivery techniques based on these mucoadhesive polymers are gaining traction and have immense potential as a prospective treatment for late-stage oral cancer. This review examines leading research in mucoadhesive polymers and discusses their potential applications in treating oral cancer.     

In silico Structure Modeling and Comparative Analysis of Characterization Properties of Protein Polymers Useful for Protein-Based Nano Particulate Drug Delivery Systems (NPDDS): A Bioinformatics Approach

With an increasing interest in nanoparticulate delivery systems, there is a greater need to identify biomaterials that are biocompatible and safe for human applications. Protein polymers from animal and plant sources are promising materials for designing nanocarriers. Composition of the protein plays an important role for specific drug delivery applications such as drug release, targeting, and stimuli responsive drug release. An important issue in protein polymers is characteristics such as size, charge, and hydrophobicity may play a significant role in phagocytic uptake and initiating a subsequent immune response. This remains to be investigated systematically by analyzing factors that influence nanoparticle characteristics of protein and reduce phagocytic uptake and does not initiate immune response too. Although protein polymers are biodegradable, it is essential to ensure that there must not be premature enzymatic breakdown of the protein nanoparticles in the systemic circulation. Surface modification of the protein nanoparticles can be used to address this issue to propose the necessary modification in the surface of the protein would be great contribution in the nano particulate drug delivery systems (NPPDS). Of the various proteins, gelatin and albumin have been widely studied for drug delivery applications. Plant proteins are yet to be investigated widely for drug delivery applications so there is need to find out the plant proteins capable to act as nanoparticles. The commercial success of albumin-based nanoparticles has created an interest in other proteins. An increased understanding of the physicochemical properties coupled with the developments in rDNA technology will open up new opportunities for protein-based nanoparticulate systems. In the present studies several proteins currently useful for drug delivery system were structurally modeled and has been analyzed to propose the essential characteristics of protein for protein-based NPDDS.     

Application of <Emphasis Type="Italic">In Situ</Emphasis> Polymerization for Design and Development of Oral Drug Delivery Systems

Although preformed polymers are commercially available for use in the design and development of drug delivery systems, in situ polymerization has also been employed. In situ polymerization affords the platform to tailor and optimize the drug delivery properties of polymers. This review brings to light the benefits of in situ polymerization for oral drug delivery and the possibilities it provides to overcome the challenges of oral route of administration.     

Polymers in drug delivery

Advances in polymer science have led to the development of several novel drug-delivery systems. A proper consideration of surface and bulk properties can aid in the designing of polymers for various drug-delivery applications. Biodegradable polymers find widespread use in drug delivery as they can be degraded to non-toxic monomers inside the body. Novel supramolecular structures based on polyethylene oxide copolymers and dendrimers are being intensively researched for delivery of genes and macromolecules. Hydrogels that can respond to a variety of physical, chemical and biological stimuli hold enormous potential for design of closed-loop drug-delivery systems. Design and synthesis of novel combinations of polymers will expand the scope of new drug-delivery systems in the future.     

Intracellular signal-responsive artificial gene regulation for novel gene delivery

We describe two types of artificial gene-regulation systems responding to cyclic AMP-dependent protein kinase (PKA) or caspase-3. These molecular systems use newly synthesized cationic polymers, PAK and PAC. The PAK polymer includes substrate oligopeptide for PKA, ARRASLG, as receptor of PKA signal, while the PAC polymer possesses oligopeptide that is comprised of a substrate sequence of caspase-3, DEVD, and a cationic oligolysine, KKKKKK. These polymers formed stable complexes with DNA to totally suppress the gene expression. However, PKA or caspase-3 signal disintegrates the PAK-DNA or the PAC-DNA complex, respectively. This liberates the DNA and activated the gene expression. These systems are the first concept of an intracellular signal-responsive gene-regulation system using artificial polymer. We expect that these systems can be applied to the novel highly cell specific gene delivery strategy that is involved in our previously proposed new drug delivery concept, the drug delivery system based on responses to cellular signals.