功能高分子在新型给药系统中的应用

功能高分子材料具有独特的物理和化学性能,近年来在各类给药系统中有着广泛的应用。该文对功能高分子在新型给药系统中的应用及研究进展进行了评述;结合具体药物剂型,针对不同给药系统的特点和实际需要以及功能高分子的相关特性,讨论了功能高分子材料在药物控缓释中的独特作用和在不同给药系统中的应用前景。     

Advances in drug delivery systems based on synthetic poly(hydroxybutyrate) (co)polymers

Within the general context of nanomedicine, drug delivery systems based on polymers have sparked a rapidly growing interest and raised many efforts to tackle various diseases, among which cancer. Polyester-based nanoparticulate drug delivery systems, including polymer-drug conjugates and amphiphilic block copolymers, represent a major class with promising outcomes, especially for those derived from poly(3-hydroxybutyrate) (PHB). This review describes recent advances in drug delivery systems designed from the self-assembly of synthetic (co)polymers derived from PHB. The various strategies for the synthesis of PHB-conjugates, PHB/poly(ethylene glycol) (PEG) and other PHB-based copolymers are first summarized. Nanoparticles, micelles, microparticles, and hydrogels elaborated from these (co)polymers following various preparation methods, along with their exploitation in the encapsulation and release of various therapeutic agents, are next detailed. Finally, we discuss the synthetic challenges, drug delivery outlooks, and perspectives of PHB-based drug delivery systems. Engineered nano-scaled materials based on PHB self-assembled systems are thus anticipated to emerge as a valuable platform for original drug delivery systems.     

Current trends in redox polymers for energy and medicine

Polymers with redox properties are electroactive macromolecules containing localized sites or groups that can be oxidized (loss of electrons) and reduced (gain of electrons). This review highlights trends in the chemistry, characterization and application of polymers with redox properties. In the first part, we overview the synthetic advances in the design of innovative redox polymers. Special attention is given to state-of-art techniques for the characterization of redox polymers and their important properties are also explained. The last part is devoted to the redox polymers applied in energy and medicine. First, the main redox polymers investigated in energy technologies such as batteries, supercapacitors, solar cells, biofuel cells or thermoelectric cells are reviewed. Second, the emerging applications of redox polymers in medicine technologies such as drug delivery, biosensors, actuators or smart surfaces are explained in detail.     

Stimuli-accelerated polymeric drug delivery systems

The controlled delivery of active pharmaceutical ingredients to the site of disease represents a major challenge in drug therapy. Particularly when drugs have to be transported across biological barriers, suitable drug delivery systems are of importance. In recent years responsive delivery systems have been developed which enable a controlled drug release depending on internal or external stimuli such as changes in pH, redox environment or light and temperature. In some studies delivery systems with reactivity against two different stimuli were established either to enhance the response by synergies of the stimuli or to broaden the window of possible trigger events. In the present review numerous exciting developments of pH-, light- and redox-cleavable polymers suitable for the preparation of smart delivery systems are described. The review discusses the different stimuli that can be used for a controlled drug release of polymer-based delivery systems. It puts a focus on the different polymers described for the preparation of stimuli-sensitive systems, their preparation techniques as well as their stimuli-responsive degradation. © 2022 The Authors. Polymer International published by John Wiley & Sons Ltd on behalf of Society of Industrial Chemistry.     

Semi-solid materials for controlled release drug formulation: current status and future prospects

Semi-solid materials represent an important category of inactive ingredients (excipients) of pharmaceutical products. Here we review several common semisolid polymers currently used in the controlled release formulations of many drugs. These polymers are selected based on their importance and broad scope of application in FDA-approved drug products and include several polysaccharides (cellulose, starch, chitosan, alginate) and carbomers, a group of mucoadhesive synthetic polymers. Glyceride-based polymers used in self-emulsifying drug delivery systems (SEDDS) will also be discussed for its importance in formulating poorly water-soluble drugs. Unique features and advantages of each type of semi-solid materials are discussed and examples of their use in oral delivery of drugs are provided. Finally, future prospects of developing new and better semi-solid excipients are discussed with the objective of facilitating clinical translation.     

PEGylated chitosan derivatives: Synthesis, characterizations and pharmaceutical applications

This review sets out to describe and discuss the synthetic approaches and the fields of application of PEGylated chitosan copolymers especially for medical use. The PEGylation of chitosan and chitosan derivatives is able to add new physicochemical properties to the cationic polysaccharide polymers, thereby overcoming some limitations, especially regarding their solubility and their use in drug and gene delivery (DNA and siRNA). All methods of derivatization have been considered and described together with the different methods of characterization of the copolymers. The capacities of PEGylated chitosan to reduce chitosan toxicity, to enhance membrane permeation and to form thermosensitive hydrogels have also been discussed.     

pH responsive polymers with amino acids in the side chains and their potential applications

Design and synthesis of pH responsive polymeric materials has become an important subject in academia as well as in industrial field in recent years due to their applications in diverse field including controlled drug delivery, biomedical applications, membrane science, sensors and actuators, oil recovery, colloid stabilization, etc. Efforts have been made to incorporate stimuli‐responsive biomolecules in synthetic polymers to develop pH responsive “smart” non‐biological hybrid macromolecules with high water solubility, enhanced biocompatibility, bio‐mimetic structure and properties. This review is focused on the recent advances in side‐chain amino acid‐based pH responsive polymers synthesis and potential application aspects of these macromolecular architectures in drug and gene delivery, and other fields. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41084.     

pH‐sensitive polymeric particles as smart carriers for rebar inhibitors delivery in alkaline condition

The waste problem of the rebar inhibitors is very serious due to that it is a long time before they can exert their best effect in the concrete and they are kept losing all the time. However, there is still no effective solution to alleviate such situation. Meanwhile, drug delivery control technology based on environmental sensitive polymers has been successfully applied in biomedical fields. Thus, poly(acrylic acid)–acrylamide was synthesized as smart carrier for controlling rebar inhibitors delivery in concrete. Dipotassium hydrogen phosphate as model drug was encapsulated inside the polymeric particles via a self‐assembly process. The pH‐responsive activities of the polymeric particles were estimated by monitoring their swelling performances in solutions of different pH values and the drug delivery control characteristics were studied in simulated concrete pore solutions. The results indicate the polymeric particles deserve network structures with high porosity and exhibit excellent pH‐responsive activities, which can perform as perfect intelligent carriers whereas the releasing of the inhibitors follows the first‐order kinetic law. The work suggests a new application field of drug delivery control technology. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45886.     

Significance and strategies in developing delivery systems for bio-macromolecular drugs

Successful development of a new drug is prohibitively expensive, and is estimated to cost approximately $100–500 million US dollars for a single clinical drug. Yet, a newly developed drug can only enjoy its patent protection for 18 years, meaning that after this protected time period, any company can manufacture this product and thus the profit generated by this drug entity would reduce dramatically. Most critically, once a drug is being synthesized, its physical, chemical, and biological attributes such as bioavailability and in vivo pharmacokinetics are all completely fixed and cannot be changed. In principal and practice, only the application of an appropriately designed drug delivery system (DDS) is able to overcome such limitations, and yet the cost of developing a novel drug delivery system is less than 10% of that of developing a new drug. Because of these reasons, the new trend in pharmaceutical development has already begun to shift from the single direction of developing new drugs in the past to a combined mode of developing both new drugs and innovative drug delivery systems in this century. Hence, for developing countries with relatively limited financial resources, a smart strategic move would be to focus on the development of new DDS, which has a significantly higher benefit/risk ratio when comparing to the development of a new drug. Because of the unmatched reaction efficiency and a repetitive action mode, the therapeutic activity of a single bio-macromolecular drug (e.g., protein toxins, gene products, etc.) is equivalent to about 10⁶–10⁸ of that from a conventional small molecule anti-cancer agent (e.g., doxorubicin). Hence, bio-macromolecular drugs have been recognized around the world as the future “drug-of-choice”. Yet, among the>10000 drugs that are currently available, only ~150 of them belong to these bio-macromolecular drugs (an exceedingly low 1.2%), reflecting the difficulties of utilizing these agents in clinical practice. In general, the bottleneck limitations of these bio-macromolecular drugs are two-fold: (1) the absence of a preferential action of the drug on tumor cells as opposed to normal tissues, and (2) the lack of ability to cross the tumor cell membrane. In this review, we provide strategies of how to solve these problems simultaneously and collectively via the development of innovative drug delivery systems. Since worldwide progress on bio-macromolecular therapeutics still remains in the infant stage and thus open for an equal-ground competition, we wish that this review would echo the desire to industrialized countries such as China to set up its strategic plan on developing delivery systems for these bio-macromolecular drugs, thereby realizing their clinical potential.     

Polybetaines in Biomedical Applications

Polybetaines, that have moieties bearing both cationic (quaternary ammonium group) and anionic groups (carboxylate, sulfonate, phosphate/phosphinate/phosphonate groups) situated in the same structural unit represent an important class of smart polymers with unique and specific properties, belonging to the family of zwitterionic materials. According to the anionic groups, polybetaines can be divided into three major classes: poly(carboxybetaines), poly(sulfobetaines) and poly(phosphobetaines). The structural diversity of polybetaines and their special properties such as, antifouling, antimicrobial, strong hydration properties and good biocompatibility lead to their use in nanotechnology, biological and medical fields, water remediation, hydrometallurgy and the oil industry. In this review we aimed to highlight the recent developments achieved in the field of biomedical applications of polybetaines such as: antifouling, antimicrobial and implant coatings, wound healing and drug delivery systems.     

Progress and Challenges in Developing Aptamer-Functionalized Targeted Drug Delivery Systems

Aptamers, which can be screened via systematic evolution of ligands by exponential enrichment (SELEX), are superior ligands for molecular recognition due to their high selectivity and affinity. The interest in the use of aptamers as ligands for targeted drug delivery has been increasing due to their unique advantages. Based on their different compositions and preparation methods, aptamer-functionalized targeted drug delivery systems can be divided into two main categories: aptamer-small molecule conjugated systems and aptamer-nanomaterial conjugated systems. In this review, we not only summarize recent progress in aptamer selection and the application of aptamers in these targeted drug delivery systems but also discuss the advantages, challenges and new perspectives associated with these delivery systems.     

影响电刺激响应型智能水凝胶弯曲行为的因素

电刺激响应型水凝胶是一类在电场作用下可以发生溶胀、收缩、变形、弯曲等行为的智能型凝胶,其中弯曲行为具有良好的应用前景。本文主要对智能型水凝胶发生弯曲行为的机理、影响因素以及在药物输送系统中的应用进行了综述并进行展望。     

Improvement of Drug Therapy by Covalent PEG Conjugation: An Overview From a Research Laboratory

In the last two decades, efforts focused in the field of drug delivery have made it possible to reach important goals, especially with proteins and peptides. The story of the evolution of this matter is vast and it is difficult to summarize its various aspects in a single review. On the other hand, it could be really interesting to look at the inside story of a typical academic research lab that has dedicated almost all its resources to drug delivery. In our case, an initial interest in the issue of protein conformation stability soon paved the way for a new area of study: the modification of proteins with synthetic polymers. We have seen this technique transformed from a crude and inhomogeneous procedure into a well-recognized and successful approach. This great advance has been possible thanks to the development of dedicated chemical coupling methods and to the better understanding of the behavior of polymers in vivo. In particular, among the several polymers investigated, PEG has became the best polymer for protein modification. Exploiting the unique properties of this polymer, we have conducted several investigations in the field of protein PEGylation and then transferred the acquired know-how to the development of conjugates with low molecular weight drug. This last aspect still presents several unmet needs that are awaiting proper solutions.     

In Vivo Applications of Molecularly Imprinted Polymers for Drug Delivery: A Pharmaceutical Perspective

Molecularly imprinted polymers (MIPs) have been proven to be a promising candidate for drug delivery systems (DDS) due to their ability to provide a sustained and controlled drug release, making them useful for treating a wide range of medical conditions. MIP-based DDS offer many advantages, including the administration of a smaller drug doses, due to the higher drug payload or targeted delivery, resulting in fewer side effects, as well as the possibility of attaining high concentrations of the drug in the targeted tissues. Whether designed as drug reservoirs or targeted DDS, MIPs are of great value to drug delivery as conventional drug formulations can be redesigned as DDS to overcome the active pharmaceutical ingredient’s (APIs) poor bioavailability, toxic effects, or other shortcomings that previously made them less efficient or unsuitable for therapy. Therefore, MIP design could be a promising alternative to the challenging research and development of new lead compounds. Research on MIPs is primarily conducted from a material science perspective, which often overlooks some of their key pharmaceutical requirements. In this review, we emphasize the specific features that make MIPs suitable for clinical use, from both a material science and a biopharmaceutical perspective.     

One dose or two? The use of polymers in drug delivery

Controlled‐release delivery systems are designed to prolong the release of drugs within the body. They consist of drug molecules encapsulated within biodegradable polymers which degrade safely into small, non‐toxic fragments, resulting in the release of the drug. Because different polymers have different degradation times, the system can be tailored to achieve the desired release rate and this can be very useful in treatments where daily dosing is required, such as epilepsy. Despite this obvious advantage, there are problems with this type of delivery, including an increased risk of overdosing. This article examines the pros and cons of controlled‐release drug‐delivery systems. Copyright © 2007 Society of Chemical Industry     

Star polymers for gene delivery

Star polymers are hyperbranched polymers with fascinating properties and exhibiting self‐assembly behaviour that have recently attracted a lot of interest in the field of gene delivery. This perspective aims to summarize the latest studies of star polymers as gene delivery vectors. Specifically, the aim is to identify and discuss the main synthetic methodologies that are used to fabricate star polymers and which structural characteristics affect their ability to be used as gene delivery agents. © 2014 Society of Chemical Industry     

智能响应型纳米药物载体的研究进展

近年来智能响应型纳米药物载体在抗肿瘤药物的递送中得到了广泛关注。该文根据智能响应型纳米药物载体是否具有主动靶向性,将其分为非靶向智能响应型纳米药物载体和靶向智能响应型纳米药物载体,并分别对这两者纳米药物载体的新研究和新进展进行了综述。同时,总结了智能响应型纳米药物载体当前存在的问题。与非靶向智能响应型纳米药物载体相比,靶向智能响应型纳米药物载体具有更多的优势,尤其是靶向肿瘤组织中特异性过表达酶的智能响应型纳米药物载体将会是今后纳米药物载体研究的一个重要方向。     

Techniques for the Assessment of Mucoadhesion in Drug Delivery Systems: An Overview

Abstract

In recent years mucoadhesive drug delivery systems have been developed for oral, buccal, nasal, ocular, rectal and vaginal routes for either systemic or local effects. Mucoadhesive drug delivery systems are presently being explored because of their potential advantages including increased residence time of the drug at the site of application, relatively rapid uptake of the drug into the systemic circulation, and enhanced bioavailability of the therapeutic agents. This review focuses on trends and techniques for mucoadhesion assessment which includes various experimental methods that have been used for the characterization of mucoadhesive polymers and/or delivery systems. These techniques are categorized into two methods, namely methods for mechanism assessment and methods for formulation evaluation. The techniques used to evaluate mecha nisms of mucoadhesion include atomic force microscopy, texture analysis, rheological, wetting and zeta potential measurements for the assessment of interactions between the mucoadhesive polymer/system and mucosal surface. The methods for the evaluation of mucoadhesion based formulations are also further classified as ex vivo, in vitro as well as pharmacokinetic methods. Hence, the techniques highlight the possibility of evaluating mucoadhesion phenomenon in spite of its complexity.     

Polyphophazenes as anti-cancer drug carriers: From synthesis to application

Currently, most of administered anti-cancer drugs are low molecular weight compounds (as compare to polymers) and hydrophobic in nature. Such small molecular anti-cancer drugs possess fast clearance rate from the blood circulating system and have toxic side effects. Poly(organophosphazenes) have wide range of biomedical applications owing good biocompatibility, sustainability and degradability into non-toxic by-products. So, in this review, we have carefully selected such poly(organophosphazenes), which proved to be good anti-cancer drug carriers because of overcoming crucial issues related to the administration of anti-cancer drugs i.e. poor hydrophilicity, lack of cancer cells specificity, and fast clearance rate from blood circulating system. Thence, the main focus of this review is to highlight the advancement that have been achieved in the synthesis of poly(organophosphazenes) and their application in anti-cancer drug delivery system (DDS).     

In vitro degradation behavior of biodegradable 4-star micelles

Drug delivery vectors for sustained release include a variety of polymeric constituents, both natural and synthetic. Among synthetic polymers several linear block copolymer systems have been explored for use as drug delivery vectors. Release of the pharmaceutical agent is affected by the degradation characteristics and/or by the swelling of the polymer. The goal of this study is to evaluate the degradation behavior of branched polyethylene oxide polylactide polyether ester as a drug delivery vector. Three samples of a star polyethylene oxide/polylactide copolymer with differing polylactide chain lengths were evaluated by characterizing the thermal properties of the neat polymer and in vitro degradation behavior.The thermal and morphological properties were examined by DSC, TGA and XRD. The in vitro polymeric micelle samples were observed over time by UV-vis, TEM and fluorescence. The four star PEO-PLA polymers have exceptional amphiphilic characteristics, which enable their use for a variety of applications. The polymers are thermally stable at biological conditions. In addition, the star polymers have shorter degradation times as compared to previously reported linear PLA and PEG-PLA copolymers, suggesting use as a short-term drug release agent. The four star PEO/PLA copolymer may be an excellent candidate for drug delivery applications.