pH敏感型聚合物胶束作为药物载体研究进展

近年来,刺激响应型聚合物胶束作为纳米药物载体因其独特的优势,如具有靶向性高、良好的生物相容性和毒副作用小等优势,而应用于药物靶向治疗中,其中pH敏感型聚合物胶束是基于生理条件下包载药物,特定pH条件下释放药物,而达到药物靶向释放目的。本文主要综述pH敏感型聚合物胶束的种类、特性、应用于药物靶向治疗的原理和研究进展,为开发和应用pH敏感型聚合物胶束提供参考。     

聚合物溶液自组装胶束的研究进展

双亲聚合物在选择性溶剂中通过亲水作用与疏水作用间力的平衡，可自组装形成核—壳型超分子有序结构(聚合物胶束)；通过聚合物分子设计、制备条件选择，可得到各种形态、结构和功能的聚合物胶束；将胶束进行核交联或壳交联，可使其结构得到固定，有利于进一步的物理及化学改性及应用。简要论述了各种新型聚合物的胶束特征、制备方法、影响因素及研究的最新进展及其在医药上的应用前景。     

作为药物载体的聚氨酯纳米胶束的研究进展

聚氨酯材料具有生物相容性好、合成简单且分子结构可设计性强等优点,不可降解的聚氨酯材料在生物医学领域已经得到应用。目前可生物降解聚氨酯纳米胶束用作药物载体的研究受到广泛关注。本综述主要从生物相容性、刺激响应性、靶向作用、细胞摄取能力强的聚氨酯纳米胶束这几个方面,介绍了作为药物载体的可生物降解聚氨酯纳米胶束的研究进展。     

Pluronic嵌段共聚物胶束作为靶向药物载体

聚氧乙烯 聚氧丙烯 聚氧乙烯 (PEO PPO PEO)三嵌段共聚物 (商品名为Pluronics)在水溶液中能自发生成多分子聚集的胶束 ,这些胶束主要以疏水的PPO嵌段为内核 ,PEO嵌段环绕在外构成外壳 ,这种胶束可以有效地增溶油溶性药物。Pluronic嵌段共聚物无毒、无刺激、无免疫原性 ,胶束外壳的PEO嵌段能阻止血小板的聚集。胶束尺寸和病毒相仿 ,其大小适合在体内传输。初步尝试表明 ,胶束表面嵌上合适的抗体可以将增溶了模型药物的Pluronic胶束定向输送到动物脑部 ,从而提高了药效 ,降低了副作用。实验表明 ,Pluronic嵌段共聚物胶束可能成为将多种药物导向特定部位的有效载体。     

聚合物载体及胶束载药控释靶向研究进展

近年来,聚合物纳米载体受到各领域的广泛关注。其中,胶束因其自组装形成特殊的核壳结构,成为研究的热点。本文简单介绍了聚合物药物载体,总结了胶束在自组装载药、响应性控释和靶向性传递方面相关研究进展。     

聚合物胶束的稳定性及影响因素

由两亲性大分子自行组装形成的聚合物胶束被广泛地应用于抗肿瘤药物的靶向输送,但是聚合物胶束纳米载药系统面临着困境,即胶束进入人体内后其稳定性大大减弱,导致药物的提前释放从而失去了靶向作用。因此阐明影响聚合物胶束稳定性因素是进一步设计和制备物理稳定的聚合物胶束药物输送载体的基础。本文从热力学和动力学角度概述聚合物胶束稳定性的影响因素,并进一步探讨了其作为重要的药物输送载体在人体血液循环系统中受到血液微环境等不利因素的影响。     

刺激响应性聚合物纳米胶束在药物控释中的应用研究

聚合物纳米胶束不仅可以提高药物的溶解度、生物利用度,延长药物在人体内的循环时间,还可以有效控制药物的释放而实现靶向治疗效果,极大地减少药物对人体的副作用。通过嵌段共聚物的纳米工程,可制备出具有细胞或组织靶向性且对物理或化学刺激敏感的高分子药物载体。本文综述了对pH值、温度、超声波和光具有响应性的聚合物纳米胶束的制备及其在药物控制释放领域的应用。     

超支化聚合物载体在药物释放体系中的应用进展

超支化聚合物具有高度支化的三维椭球状立体结构,分子内部呈多孔状,外围富集大量的末端活性基团,结构紧凑,整个分子无链段缠绕,溶液和熔体粘度低、反应活性高、溶解性好、低毒、可生物降解、无免疫原性,作为药物载体材料具有良好研究价值和发展前景。本文对超支化聚合物作为高分子药物载体材料在药物释放体系中的应用进行了综述。     

细胞靶向抗肿瘤纳米药物载体的研究进展

肿瘤已经成为严重危害人类健康的重大疾病之一,而如何治疗肿瘤疾病已逐渐变为近年内的研究热点。由于纳米药物载体在细胞靶向抗肿瘤中表现出来的特殊性质,使其受到了越来越多的关注。本文将就一些常见的纳米药物载体作一综述。     

Polymeric PEGylated nanoparticles as drug carriers: How preparation and loading procedures influence functional properties

The application of emerging nanotechnologies in medicine showed in the last years a significant potential in the improvement of therapies. In particular, polymeric nanocarriers are currently tested to evaluate their capability to reduce side effects, to increase the residence time in the body and also to obtain a controlled release over time. In the present work a novel polymeric nanocarrier was developed and optimized to obtain, with the same chemical formulation, three different typologies of nanocarriers: dense nanospheres loaded with an active molecule (1) during nanoparticle formation and (2) after the preparation and (3) hollow nanocapsules to increase the starting drug payload. Synthetic materials considered were PEGylated acrylic copolymers, folic acid was used as model of a hydrophobic drug. The main aim is to develop an optimized nanocarrier for the transport and the enhanced release of poorly water‐soluble drugs. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41310.     

Polymeric micelles based on photocleavable linkers tethered with a model drug

An amphiphilic block copolymer with photocleavable nitrobenzyl moieties in the side chain of the hydrophobic block was successfully synthesized by a combination of atom transfer radical polymerization (ATRP) and the Cu(I)-catalyzed 1,3-dipolar cycloaddition of azide and alkynes. 2-(Trimethylsilyloxy)ethyl methacrylate (HEMATMS) was polymerized from a poly(ethylene oxide) (PEO) macroinitiator via ATRP, leading to a well-defined block copolymer of PEO₁₁₃-b-PHEMATMS₄₅ with low polydispersity index (PDI = 1.09). After the polymerization, trimethylsilyl (TMS) groups were deprotected and then functionalized in-situ with 3-azidopropionic chloride to yield PEO-b-[2-(1-azidobutyryloxy)ethyl methacrylate] (PEO-b-PAzHEMA). Alkyne-functionalized pyrene with a photocleavable 2-nitrobenzyl moiety was added to the PEO-b-PAzHEMA backbone via click chemistry to produce the desired block copolymer with high fidelity. The resulting block copolymer was self-assembled in water to yield spherical micelles with an average diameter of 60 nm. Upon UV irradiation, 2-nitrobenzyl moieties were selectively cleaved, leading to the release of a model drug, 1-pyrenebutyric acid. Coumarin 102, another model drug that was physically encapsulated in the core of micelles during micellization in water, was also released at the same time. The general strategy presented herein can potentially be utilized for the preparation of polymeric vehicles that are capable of delivering multiple therapeutics under controlled individual release kinetics.     

Biodegradable polylactide/poly(ethylene glycol)/polylactide triblock copolymer micelles as anticancer drug carriers

Adriamycin (ADR) was selected as a model drug to evaluate the potential applications of polylactide/poly(ethylene glycol)/polylactide (PLA/PEG/PLA) micelles as drug carriers in parenteral delivery systems. The PLA/PEG/PLA triblock copolymer micelles were characterized by dynamic light scattering and transmission electron microscopy. It was found that the micelle size increased with the increasing of the PLA chain length. The average size of ADR‐loaded micelles was 143.2 nm. The histogram analysis showed that the ADR‐loaded micelles possessed a narrow unimodal size distribution. The ADR loading contents of the micelles and ADR entrapment efficiency were dependent on the PLA chain length and PEG chain length in the copolymer. They increased with the increase of the PLA chain length, but the PEG chain length was identical and decreased with the increase of the PEG chain length; the length of the PLA block was similar. The initial amount of ADR also influenced the drug contents and entrapment efficiency (i.e., the more the initial amount added, the more the drug contents and the higher encapsulation efficiency). The drug release experiments indicated that the ADR‐loaded micelles possessed sustained release characteristics. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 80: 1976–1982, 2001     

Polymeric vesicles: from drug carriers to nanoreactors and artificial organelles

One strategy in modern medicine is the development of new platforms that combine multifunctional compounds with stable, safe carriers in patient-oriented therapeutic strategies. The simultaneous detection and treatment of pathological events through interactions manipulated at the molecular level offer treatment strategies that can decrease side effects resulting from conventional therapeutic approaches. Several types of nanocarriers have been proposed for biomedical purposes, including inorganic nanoparticles, lipid aggregates, including liposomes, and synthetic polymeric systems, such as vesicles, micelles, or nanotubes. Polymeric vesicles--structures similar to lipid vesicles but created using synthetic block copolymers--represent an excellent candidate for new nanocarriers for medical applications. These structures are more stable than liposomes but retain their low immunogenicity. Significant efforts have been made to improve the size, membrane flexibility, and permeability of polymeric vesicles and to enhance their target specificity. The optimization of these properties will allow researchers to design smart compartments that can co-encapsulate sensitive molecules, such as RNA, enzymes, and proteins, and their membranes allow insertion of membrane proteins rather than simply serving as passive carriers. In this Account, we illustrate the advances that are shifting these molecular systems from simple polymeric carriers to smart-complex protein-polymer assemblies, such as nanoreactors or synthetic organelles. Polymeric vesicles generated by the self-assembly of amphiphilic copolymers (polymersomes) offer the advantage of simultaneous encapsulation of hydrophilic compounds in their aqueous cavities and the insertion of fragile, hydrophobic compounds in their membranes. This strategy has permitted us and others to design and develop new systems such as nanoreactors and artificial organelles in which active compounds are simultaneously protected and allowed to act in situ. In recent years, we have created a variety of multifunctional, proteinpolymersomes combinations for biomedical applications. The insertion of membrane proteins or biopores into the polymer membrane supported the activity of co-encapsulated enzymes that act in tandem inside the cavity or of combinations of drugs and imaging agents. Surface functionalization of these nanocarriers permitted specific targeting of the desired biological compartments. Polymeric vesicles alone are relatively easy to prepare and functionalize. Those features, along with their stability and multifunctionality, promote their use in the development of new theranostic strategies. The combination of polymer vesicles and biological entities will serve as tools to improve the observation and treatment of pathological events and the overall condition of the patient.     

树枝状大分子用于药物载体的研究进展

树枝状大分子是近年来出现的一类新型合成纳米高分子,具有可控的三维高度支化结构、表面分布着大量的功能基团和单分散等特点,使其在生物医学等领域中日益受到广泛关注。作为一种新型非生物载体,树枝状大分子内部空腔和表面功能基团均可与药物复合,在药物输送和基因转运等方面具有广阔的应用前景。     

Alkylated pectin hydrogels as potential protein drug carriers

Pectin has been used in the development of safe and effective drug delivery systems because of its unique physicochemical and biological characteristics. However, it still needs to be modified to overcome some inherent drawbacks. In the present study, pectin was alkylated by bromododecane. The C₁₂‐alkylated pectin (PC₁₂) can form strong hydrogels in the presence of Ca²⁺. Such hydrogels were explored to prepare bovine serum albumin (BSA)‐loaded microspheres (PC₁₂‐MS). The BSA encapsulation yield of PC₁₂‐MS was significantly higher than that of microspheres prepared with the original pectin (PC‐MS). Differential scanning calorimetry analysis indicated that interactions existed between BSA and pectin during the preparation of microspheres. Release tests showed that PC₁₂‐MS almost avoided BSA release in simulated gastric fluids, which was verified by environmental scanning electron microscopy analysis, and exhibited an effective controlled release throughout the simulated gastrointestinal tract compared to PC‐MS. In addition, an MTT assay showed the biocompatibility of C₁₂‐alkylated pectin. Thus alkylated pectin may serve as a potential protein drug carrier. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45344.     

Polymeric drug carriers functionalized with pairwise arranged hydroxyl and/or carboxyl groups for platinum chelation

Cancer chemotherapy, alone or in combination with other treatment modalities, has come to play an important part in the fight against malignancies. However, the anticancer drugs in current clinical administration, while efficacious and oftentimes curative against a select number of neoplasias, suffer from a variety of deficiencies, notably severe systemic toxicity and a tendency to elicit drug resistance. These pharmacological shortcomings are eminently in evidence with the outstanding class of platinum drugs as represented by cis‐diaminedichloroplatinum(II) (cisplatin). The bioreversible binding (conjugating) of a medicinal agent to a water‐soluble macromolecular carrier has been recognized as an effective expediency to curtail these deficiencies. In the present communication we describe the synthesis of a special class of polymers featuring hydroxyl and/or carboxyl functionalities designed for use in the construction of square‐planar platinum complexes polymer‐bound through dihydroxylato, hydroxylatocarboxylato, or dicarboxylato chelation. Accordingly, the polymer structures of this project contain pairs of hydroxyl, hydroxylcarboxyl, or carboxyl groups main chain‐ or side chain‐attached in 1,2‐geometry. The target polymers are obtained by a Michael addition type polymerization of bisacrylamide monomers with mono‐ or diamine comonomers in aqueous medium. Whereas in the first three polymers the hydroxyl and/or carboxyl functionalities are attached directly (1) or close (2, 3) to the backbone, the remaining polymers contain these functionalities as terminals on extended spacer segments. The water‐soluble polymeric products, purified and fractionated by dialysis and isolated by freeze‐drying, will be used as substrates for platinum conjugation in future work. However, their functional proneness to platinum binding is demonstrated in the present project through platination of an exemplifying carrier, providing a water‐soluble conjugate with a Pt content of 13.5%. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 10–19, 2005     

Microparticles based on hydrophobically modified chitosan as drug carriers

In this work, a hydrophobically modified (HM) chitosan derivative was prepared by covalent linkage of C₁₂ groups to the chitosan backbone. HM‐chitosan microparticles were prepared according to an emulsification‐solvent evaporation method and naltrexone (NTX) was used as a model drug. For comparison, unmodified chitosan and poly lactic‐co‐glycolic acid (PLGA) microparticles were also tested as carriers for NTX. HM‐chitosan formed viscous semi‐dilute solutions, suggesting a high level of chain entanglements and hydrophobic associations. HM‐chitosan microparticles generally showed higher production yield and encapsulation efficiency, as compared with chitosan and PLGA. The burst release shown by chitosan microparticles was significantly reduced when using the HM‐chitosan derivative. An enhanced control of drug release was observed over at least 50 days. PLGA particles demonstrated inferior controlled release properties as compared to HM‐chitosan subsequent to the initial release stage. These results revealed the potential of hydrophobic modification of chitosan as a means to improve the stability and sustained delivery properties of the polymer. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40055.     

Polymeric drugs carriers of methacrylic and acrylic derivatives

Summary 2-Amino-thiazole reacts with methacryloyl or acryloyl chloride to give amides which are polymerized. Hydrolyses of polymers have been studied with and without enzymatic catalysis in a synthetic gastric liquid.     

Preparation and characterization of inulin ester microspheres as drug carriers

Acetylated and succinoylated inulin were synthesized by reacting inulin with acetic anhydride and succinic anhydride. The modified inulin was characterized by FTIR, NMR, and potentiometric titration. The compositional dependence of their properties, such as solubility, pKa, and melting point, was investigated. The results reveal that the solubility of the inulin derivatives in pH 7.4 buffer solution increases with the succinyl content, varying from negligible for fully acetylated inulin to over 54% for fully succinoylated inulin, whereas the corresponding pKa of the inulin derivatives decreases with increasing succinyl content. In addition, the melting point is lowered by acetylation and/or succinoylation. The influence of pH and ionic strength on the solubility of inulin acetate succinate was also studied. The solubility increases dramatically as the pH value approaches that of the pKa. Interestingly, in pH 7.4 buffer solutions of varying ionic strength, a maximum solubility appears at an ionic strength of 0.15M. This is interpreted as a result of a balance of the ion exchange process and the double layer suppression. Microspheres of inulin acetate and inulin acetate succinate with and without drug were prepared by the solvent precipitation method. Cationic compounds, chlorhexidine and chymotripsin, were used as model drugs. The size and morphology of microspheres were determined by scanning electron microscope. The microspheres range in diameters from 0.5 to 4 μm for inulin acetate and inulin/chymotripsin microspheres, and from 90 to 130 μm for inulin acetate/chlorhexindine microspheres. The cross‐section of the microspheres exhibits a porous interior. Preliminary results show that the microspheres are able to release the incorporated drugs for an extended period of time. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 77: 833–840, 2000