医用壳聚糖膜的制备与应用

背景：壳聚糖膜在人工肾膜-透析膜、人工皮肤、口腔溃疡膜、牙周引导组织再生膜、药物载体控释膜及相关组织工程等方面已取得了令人欣慰的成果。 目的：总结归纳壳聚糖膜的制备,及目前其在用于局部药物控释的应用。 方法：电子检索CNKI数据库、读秀学术搜索等数据库收录的壳聚糖膜的制备和应用于药物控释载体的相关综述和实验研究报告,分析壳聚糖制备的研究进展和应用于药物控释载体的研究进展。 结果与结论：共纳入壳聚糖制备与局部药物控释相关文献21篇。壳聚糖的制备条件与其应用于药物控释载体之间有着密不可分的关系,但总结规范及其相关性尚不明朗,尚期待大量研究。对壳聚糖的制备条件与其应用于药物控释载体的关系的研究也仍需要进一步努力,探索适宜壳聚糖膜制备条件,制备成功最适的药物控释载体是研究者的工作重点。     

药物基因组学临床决策支持系统综述

近几年来精准医学成为生物医学的一个热门领域,世界各国都致力于率先在这一领域取得突破性的进展。药物基因组学(PGx),通过基因组学和其他“组学”知识来个性化药物选择和药物使用以避免药物不良反应和最大化药物疗效,是精准医学的重要组成部分,也是目前最有希望在临床上实现日常应用的精准医学领域之一。其中药物基因组学临床决策支持(PGx-CDS)系统,是实现PGx临床应用和知识转化必不可少的工具。目前很多临床医疗机构已经开展PGx服务并部署PGx-CDS系统,同时更多的临床医疗和研究机构正在筹备开展这类服务。对目前已出现并被报道的主要PGx-CDS系统和研究进行文献综述,共涉及11个PGx-CDS系统。通过对这些系统的临床应用场景、系统设计、知识表达、干预方式和应用评估等方面的综合回顾,总结目前PGx-CDS系统的研究进展和发展现状,然后对PGx-CDS系统目前面临的主要挑战和未来发展方向进行讨论,为在国内落地PGx服务和PGx-CDS系统提供借鉴。     

Microfabricated Drug Delivery Systems: Concepts to Improve Clinical Benefit

Important classes of drugs have yet to benefit from advances in drug delivery technology. Strategies to provide reasonable oral bioavailability of peptide and proteins drugs remain elusive, for example. Systemic cancer drugs produce dose-limiting toxicities largely due to their lack of selectivity. Although delivery systems such as immunotoxins and liposomes improve selectivity of a few cancer drugs, current technology is not suitable for the vast majority of such molecules. Systems able to mimic the body's natural feedback mechanisms for secretion of hormones such as insulin represents yet another unmet medical need. Microfabrication techniques may permit the creation of drug delivery systems that possess a combination of structural, mechanical, and perhaps electronic features which may surmount some of these challenges. In this review, drug delivery concepts are presented which capitalize on the strengths of microfabrication. Possible applications include micromachined silicon membranes to create implantable biocapsules for the immunoisolation of pancreatic islet cells—as a possible treatment for diabetes—and sustained release of injectable drugs needed over long time periods. Asymmetrical, drug-loaded microfabricated particles with specific ligands linked to the surface are proposed for improving oral bioavailability of peptide (and perhaps protein) drugs. Similarly designed particles with sizes in the 2–10 m range may be safe to administer intravenously and a clinical strategy is suggested for using such microparticles for treating solid tumors. Although hypothetical now, work is in progress to prove the concepts presented here and to validate the intuitive belief that there is an important place for microfabricated systems in drug delivery.     

Biomaterials for drug delivery systems

Drug delivery systems have unusual materials requirements which derive mainly from their therapeutic role: to administer drugs over prolonged periods of time at rates that are independent of patient-to-patient variables. The chemical nature of the surfaces of such devices may stimulate biorejection processes which can be enhanced or suppressed by the simultaneous presence of the drug that is being administered. Selection of materials for such systems is further complicated by the need for compatibility with the drug contained within the system. A review of selected drug delivery systems is presented. This leads to a definition of the technologies required to develop successfully such systems as well as to categorize the classes of drug delivery systems available to the therapist. A summary of the applications of drug delivery systems will also be presented. There are five major challenges to the biomaterials scientist: (1) how to minimize the influence on delivery rate of the transient biological response that accompanies implantation of any object; (2) how to select a composition, size, shape, and flexibility that optimizes biocompatibility; (3) how to make an intravascular delivery system that will retain long-term functionality; (4) how to make a percutaneous lead for those delivery systems that cannot be implanted but which must retain functionality for extended periods; and (5) how to make biosensors of adequate compatibility and stability to use with the ultimate drug delivery system-a system that operates with feedback control.     

Liposomal drug delivery system from laboratory to clinic

The main objective of drug delivery systems is to deliver a drug effectively, specifically to the site of action and to achieve greater efficacy and minimise the toxic effects compared to conventional drugs. Amongst various carrier systems, liposomes have generated a great interest because of their versatility. Liposomes are vesicular concentric bilayered structures, which are biocompatible, biodegradable and nonimmumnogenic. They can control the delivery of drugs by targeting the drug to the site of action or by site avoidance drug delivery or by prolonged circulation of drugs. Amphotericin B (Amp B) remains the drug of choice in most systemic mycoses and also as a second line treatment for Kala azar. However, its toxic effects often limit its use. Although the liposome delivery system has been tried for several drugs, only a few have been used in patients due to the slow development of necessary large-scale pharmaceutical procedures. This paper reviews the development of the technique for liposomal Amphotericin B (L-Amp-LRC-1, Fungisome) drug delivery system in our laboratory in collaboration with the department of Biochemistry, Delhi University in India and proving the safety and efficacy of this preparation in clinical practice. It also attempts to compare the efficacy and benefits of our product for Indian patients with those of similar products and it includes facts from the publications that flowed from our work. As compared to conventional Amp B, Fungisome is infused over a much shorter period requiring a smaller volume and no premedication. It was found to be safe in patients who had developed serious unacceptable toxicity with conventional Amp B. In renal transplant patients, Fungisome did not produce any nephrotoxicity. Fungisome is effective in fungal infections resistant to fluconazole, conventional Amp B and in virgin and resistant cases of visceral leishmaniasis. The cost of any drug is of great significance, especially in India. We have therefore devoted a section of our review to the relative costs of our product and those of other commercially available products. This patient-worthy formulation is safe, efficacious and cheaper than the commercially available formulation of liposomal amphotericin B. The product has been patented and technology transferred to a pharmaceutical company for marketing. Results of postmarketing study also document safety and efficacy as observed in premarketing studies. A brief review of this work is provided here.     

Diffusivity of 125I-labelled macromolecules through collagen: mechanism of diffusion and effect of adsorption

Diffusion of angiotensin II, albumin and aldolase was studied through collagen membranes with swelling ratios between 4 and 15. The diffusion coefficient was measured from the time-lag for the onset of steady-state flux through the membrane. Binding of macromolecules to collagen was evaluated from the results of sorption studies conducted as a function of macromolecular concentration. Results presented indicate that the diffusion of macromolecules through collagen membrane is slowed by electrostatic and hydrogen bonding between individual macromolecular chains and collagen. The extent of adsorption is increased as the molecular weight of the diffusant increases. Diffusion of water soluble macromolecules through collagen occurs rapidly, suggesting that diffusion occurs through water filled channels as opposed to between collagen molecules. The results of these studies are useful in understanding diffusion through connective tissues and in the design of drug delivery systems based on collagen.     

Bioelectric effects of intense ultrashort pulses

Models for electric field interactions with biological cells predict that pulses with durations shorter than the charging time of the outer membrane can affect intracellular structures. Experimental studies in which human cells were exposed to pulsed electric fields of up to 300 kV/cm amplitude, with durations as short as 10 ns, have confirmed this hypothesis. The observed effects include the breaching of intracellular granule membranes without permanent damage to the cell membrane, abrupt rises in intracellular free calcium levels, enhanced expression of genes, cytochrome c release, and electroporation for gene transfer and drug delivery. At increased electric fields, the application of nanosecond pulses induces apoptosis (programmed cell death) in biological cells, an effect that has been shown to reduce the growth of tumors. Possible applications of the intracellular electroeffects are enhancing gene delivery to the nucleus, controlling cell functions that depend on calcium release (causing cell immobilization), and treating tumors. Such nanosecond electrical pulses have been shown to successfully treat melanoma tumors by using needle arrays as pulse delivery systems. Reducing the pulse duration of intense electric field pulses even further into the subnanosecond range will allow for the use of wideband antennas to deliver the electromagnetic fields into tissue with a spatial resolution in the centimeter range. This review carefully examines the above concepts, provides a theoretical basis, and modeling results based on both continuum approaches and atomistic molecular dynamics methods. Relevant experimental data are also presented, and some of the many potential bioengineering applications discussed.     

Functionalized ceramics for biomedical,biotechnological and environmental applications

Surface functionalization has become of paramount importance and is considered a fundamental tool for the development and design of countless devices and engineered systems for key technological areas in biomedical, biotechnological and environmental applications. In this review, surface functionalization strategies for alumina, zirconia, titania, silica, iron oxide and calcium phosphate are presented and discussed. These materials have become particularly important concerning the aforementioned applications, being not only of great academic, but also of steadily increasing human and commercial, interest. In this review, special emphasis is given to their use as biomaterials, biosensors, biological targets, drug delivery systems, implants, chromatographic supports for biomolecule purification and analysis, and adsorbents for toxic substances and pollutants. The objective of this review is to provide a broad picture of the enormous possibilities offered by surface functionalization and to identify particular challenges regarding surface analysis and characterization.     

A review of glycosylated carriers for drug delivery

Carbohydrates not only represent a vast potential as structure building blocks of living cells but also have proved as a promising candidate for drug delivery. Glycosylation of nanocarriers instructs some gratifying characteristic, which leads to the evolution of promising delivery systems. Some path-breaking advantages of glycosylated carriers include the engineered release profile of bioactives when introduced into biological system. Being natural product of living system these carriers also upshots as a multifaceted drug delivery vehicle and reduces the toxicity associated with unmodified drug carrier and therapeutic agent. An additional attribute of these carriers is to alter the pharmacokinetic profile of drugs positively with stabilization of drug carrier. The presence of lectin receptors on different cell surfaces makes the glycosylated carrier appreciable for targeted delivery of drugs to improve their therapeutic index. Active participation of some lectin receptors in immune responses to antigen overlaid the application of glycosylated carriers in delivery of antigen and immunotherapy for treatment of ailments like cancer. These advantages revealed the promising potential of glycosylated carriers in each perspective of drug delivery. Collectively this review presents an overview of different applications of glycosylated carriers, with a focus on their applicability in development of a nanoconstruct with GRAS status.     

Polymeric particulate technologies for oral drug delivery and targeting: A pathophysiological perspective

The oral route for delivery of pharmaceuticals is the most widely used and accepted. Nanoparticles and microparticles are increasingly being applied within this arena to optimize drug targeting and bioavailability. Frequently the carrier systems used are either constructed from or contain polymeric materials. Examples of these nanocarriers include polymeric nanoparticles, solid lipid nanocarriers, self-nanoemulsifying drug delivery systems and nanocrystals. It is the purpose of this review to describe these cutting edge technologies and specifically focus on the interaction and fate of these polymers within the gastrointestinal system.     

Chitosan as a barrier membrane material in periodontal tissue regeneration

Periodontal regeneration is defined as regeneration of the tooth-supporting tissues including cementum, periodontal ligament, and alveolar bone. Guided tissue regeneration (GTR) has been demonstrated to be an effective technique to achieve periodontal regeneration. In the GTR procedures, various kinds of membranes play important roles. Chitosan, a deacetylated derivative of chitin, is biocompatible, biodegradable, and antimicrobial. It acts as hydrating agent and possesses tissue healing and osteoinducing effect. Chitosan can be easily processed into membranes, gels, nanofibers, beads, nanoparticles, scaffolds, and sponges forms and can be used in drug delivery systems. Here, we review the bioproperties of chitosan and report the progress of application of chitosan as membranes in GTR and guided bone regeneration (GBR), which indicates that chitosan could be a good substrate candidate as the materials for the GTR/GBR membranes.     

高分子纳米粒子在靶向药物载体中的研究进展

高分子纳米粒子作为靶向药物的载体材料可将药物选择性地靶向病变部位 ,可以有效降低其对正常组织的毒副作用 ,提高药物的生物利用度 ,是一种新型的药物控释体系。本文综述了高分子纳米粒子在主动靶向药物、被动靶向药物、物理靶向药物载体中的应用     

MRI in ocular drug delivery

Conventional pharmacokinetic methods for studying ocular drug delivery are invasive and cannot be conveniently applied to humans. The advancement of MRI technology has provided new opportunities in ocular drug-delivery research. MRI provides a means to non-invasively and continuously monitor ocular drug-delivery systems with a contrast agent or compound labeled with a contrast agent. It is a useful technique in pharmacokinetic studies, evaluation of drug-delivery methods, and drug-delivery device testing. Although the current status of the technology presents some major challenges to pharmaceutical research using MRI, it has a lot of potential. In the past decade, MRI has been used to examine ocular drug delivery via the subconjunctival route, intravitreal injection, intrascleral injection to the suprachoroidal space, episcleral and intravitreal implants, periocular injections, and ocular iontophoresis. In this review, the advantages and limitations of MRI in the study of ocular drug delivery are discussed. Different MR contrast agents and MRI techniques for ocular drug-delivery research are compared. Ocular drug-delivery studies using MRI are reviewed.     

Molecular release from a polymeric microreservoir device: Influence of chemistry, polymer swelling, and loading on device performance

A polymeric microreservoir device for controlled-release drug delivery relies on the degradation of thin poly(lactic-co-glycolic acid) membranes that seal each reservoir to achieve pulsatile drug delivery. In vitro release studies in which the swelling of the reservoir membranes was measured indicate a correlation between the release times of various radiolabeled molecules from the devices and the time at which the maximum membrane swelling was observed. Varying the chemistry (lipophilicity/hydrophilicity) or molecular weight of the molecules loaded into the devices did not appear to affect the degree of membrane swelling that was observed, or the time at which the molecules were released from the devices. The amount of drug that was loaded into the reservoirs also did not appear to affect the observed release time of the drug from the device, a significant departure from the behavior of many matrix-type polymeric drug delivery systems.     

Membrane-sealed hollow microneedles and related administration schemes for transdermal drug delivery

This paper presents fabrication and testing of membrane-sealed hollow microneedles. This novel concept offers the possibility of a sealed microneedle-based transdermal drug delivery system in which the drug is stored and protected from the environment. Sealed microneedles were fabricated by covering the tip openings of out-of-plane silicon microneedles with thin gold membranes. In this way a leak-tight seal was established which hinders both contamination and evaporation. To allow drug release from the microneedles, three different methods of opening the seals were investigated: burst opening by means of pressure; opening by applying a small voltage in the presence of physiological saline; and opening as a result of microneedle insertion into the skin. It was found that a 170 nm thick gold membrane can withstand a pressure of approximately 120 kPa. At higher pressures the membranes burst and the microneedles are opened up. The membranes can also be electrochemically dissolved within 2 min in saline conditions similar to interstitial fluid present in the skin. Moreover, through in vivo tests, it was demonstrated that 170 nm thick membranes break when the microneedles were inserted into skin tissue. The proposed concept was demonstrated as a feasible option for sealing hollow microneedles. This enables the realization of a closed-package transdermal drug delivery system based on microneedles.     

Antigen delivery systems

Many vaccine candidates are highly purified, sometimes monomeric antigens and as a result, not very immunogenic. Antigen delivery systems optimize the presentation of antigens. They also play a major role in solving the problem of there being an increasing number of vaccines but limited opportunities in which to include these vaccines in immunization programs. The number of injections is restricted and combining vaccines may lead to immunological and physicochemical incompatibility. In this review, the current status with respect to parenteral and mucosal delivery systems is discussed. These include lipid-based systems such as liposomes and immunostimulating complexes, as well as polymeric microspheres. In addition, developments in needle-free, dermal delivery devices such as jet injectors, microneedles and patches are presented.     

环境感应型可生物降解药物控释系统的研究进展

环境感应型可生物降解药物控释系统具有智能化、效率高和使用方便等特点,在药物控制释放研究领域越来越受瞩目。本文基于国内外大量研究文献,对环境感应型可生物降解药物控释系统进行了综述,着重介绍了温度和pH敏感型可生物降解智能化高分子给药系统的研究进展。     

Molecularly imprinted cryogel membranes for mitomycin C delivery

In this study, cryogel-based implantable molecularly imprinted drug delivery systems were designed for the delivery of antineoplastic agent. Mitomycin C imprinted poly(2-hydroxyethyl methacrylate-N-methacryloyl-l-glutamic acid) cryogel membranes were produced by free-radical bulk polymerization under partially frozen conditions. The membranes were characterized by swelling tests, Fourier transform infrared spectroscopy, scanning electron microscopy, surface area measurements and in vitro hemocompatibility tests. In vitro delivery studies were carried out to examine the effects of cross-linker ratio and template content. Mitomycin C imprinted cryogel membranes have megaporous structure (10–100 μm in diameter). The cumulative release of mitomycin C was decreased with increasing cross-linking agent ratio and increased with the amount of template in the cryogel structure. The nature of transport mechanism of the mitomycin C from the membranes was non-Fickian.     

Porosity effects of natural latex (Hevea brasiliensis) on release of compounds for biomedical applications

Natural rubber latex biomedical (NRLb) obtained from the rubber tree Hevea brasiliensis has shown great potential in biomedicine and biomaterial applications. NRLb has been utilized as a physical barrier against infectious agents and in the controlled release of drugs and extracts. In the present work, NRLb was polymerized in a lyophilizer using different volumes of water to control the resultant membrane porosity and characterized regarding the surface morphology, water vapour permeability (WVP), mechanical properties, haemolytic activity and cytotoxicity. The release of bovine serum albumin protein from the latex membranes was evaluated. Drug release rates increased with porosity and membranes were able to control protein release up to 12 h. In addition, WVP increased with the quantity of pores. The cell viability observed for the porous membrane was higher than that noted for conventional membranes. In summary, the porosity control of natural latex membranes can be used to modulate properties and make them suitable for biomedical applications, such as wound dressings, modulated gas-exchange membranes and controlled drug delivery systems.