抗肿瘤药物输送系统

大多数小分子抗肿瘤药物均存在水溶性差、给药量大、体内半衰期短等问题,它们经口服或静脉注射给药后,只能通过自由扩散方式进入细胞,往往缺乏选择性,同时,对肿瘤细胞和正常细胞产生细胞毒性,具有较强的毒副作用,甚至对患者造成二次伤害。因此,它们在临床应用上受到很大限制。通过选择适宜的载体材料构筑抗肿瘤药物输送系统（如胶束、凝胶、纳米粒子等）,不仅可以延长小分子抗肿瘤药物的半衰期、降低其毒副作用,而且还可提高其溶解性和生物利用度,因而受到广大科研人员及制药企业的广泛重视。到目前为止,抗肿瘤药物输送系统的发展历史已有60多年,大致可分为传统型、智能型和靶向型三个不同的发展阶段。本文将从这三个不同发展阶段来综述抗肿瘤药物输送系统及其最新的研究进展,并对其未来的发展进行展望。     

智能水凝胶双抗癌药物控释体系

近年来,基于联合用药策略的双药物控释体系的研究为降低抗癌药物毒性和提高疗效提供了有效途径。水凝胶作为一类高临床应用价值的药物载体,在药物控释方面具有广泛的应用前景。癌症是危害人类健康和生命的疾病之一,当人体内正常细胞发生癌变后,癌变细胞周围会发生一些显著的变化。因此,根据肿瘤细胞与正常细胞在体内环境及体外环境的差异,发展了多种智能型水凝胶双抗癌药物控释载体。它能够在感知外界因素的刺激下发生内部结构的变化,从而实现对药物的可控释放。与此同时,随着新的治疗手段的兴起和更多抗癌作用靶点的发现,水凝胶载体也成功实现了化学药物和生物治疗因子的同时负载和可控释放。本文将从不同智能型水凝胶载体如何负载、控释双抗癌药物及水凝胶药物载体中药物的组合方式两方面综述智能型水凝胶双抗癌药物控释体系最新研究进展,并展望其发展前景。     

聚合物纳米粒子用于给药载体

聚合物纳米粒子用于给药载体具有广阔的前景，本文按聚合物纳米粒子的主要制备方法（单体聚合法，聚合物后分散法和两亲性聚合物自组装法等）综述了它近十年来在药物靶向输送上的应用研究进展。     

Photomechanical Polymer Nanocomposites for Drug Delivery Devices

We demonstrate a novel structure based on smart carbon nanocomposites intended for fabricating laser-triggered drug delivery devices (DDDs). The performance of the devices relies on nanocomposites’ photothermal effects that are based on polydimethylsiloxane (PDMS) with carbon nanoparticles (CNPs). Upon evaluating the main features of the nanocomposites through physicochemical and photomechanical characterizations, we identified the main photomechanical features to be considered for selecting a nanocomposite for the DDDs. The capabilities of the PDMS/CNPs prototypes for drug delivery were tested using rhodamine-B (Rh-B) as a marker solution, allowing for visualizing and quantifying the release of the marker contained within the device. Our results showed that the DDDs readily expel the Rh-B from the reservoir upon laser irradiation and the amount of released Rh-B depends on the exposure time. Additionally, we identified two main Rh-B release mechanisms, the first one is based on the device elastic deformation and the second one is based on bubble generation and its expansion into the device. Both mechanisms were further elucidated through numerical simulations and compared with the experimental results. These promising results demonstrate that an inexpensive nanocomposite such as PDMS/CNPs can serve as a foundation for novel DDDs with spatial and temporal release control through laser irradiation.     

量子点给药载体研究进展

量子点因其优良的发光性质,易于修饰的表面结构,在化学、医学和材料等研究领域显示了极其广阔的应用前景,受到科研工作者越来越多的关注。本文介绍了量子点的独特光学性质、制备方法、水溶性修饰和量子点与生物分子的偶联,重点讨论了量子点作为给药载体和给药载体标记物,以及以量子点为平台建立的多功能纳米给药体系的近年研究进展,阐述了当前研究中的主要发展方向和仍需解决的问题。     

Nanomaterials for Ocular Drug Delivery

Efficient drug delivery to the eye remains a challenging task for pharmaceutical scientists. Due to the various anatomical barriers and the clearance mechanisms prevailing in the eye, conventional drug delivery systems, such as eye drop solutions, suffer from low bioavailability. More invasive methods, such as intravitreal injections and implants, cause adverse effects in the eye. Recently, an increasing number of scientists have turned to nanomaterial‐based drug delivery systems to address the challenges faced by conventional methods. This paper highlights recent applications of various nanomaterials, such as polymeric micelles, hydrogels, liposomes, niosomes, dendrimers, and cyclodextrins as ocular drug delivery systems to enhance the bioavailability of ocular therapeutic agents.

     

萘普生在新型缓释系统中的释药

亲水凝胶;萘普生;二醋酸纤维素;致孔剂;新型药物缓释系统     

Nanostructured Lipid Carriers-Hydrogels System for Drug Delivery: Nanohybrid Technology Perspective

Advanced hybrid component development in nanotechnology provides superior functionality in the application of scientific knowledge for the drug delivery industry. The purpose of this paper is to review important nanohybrid perspectives in drug delivery between nanostructured lipid carriers (NLC) and hydrogel systems. The hybrid system may result in the enhancement of each component’s synergistic properties in the mechanical strength of the hydrogel and concomitantly decrease aggregation of the NLC. The significant progress in nanostructured lipid carriers–hydrogels is reviewed here, with an emphasis on their preparation, potential applications, advantages, and underlying issues associated with these exciting materials.     

Multivalent Aptamer-modified DNA Origami as Drug Delivery System for Targeted Cancer Therapy

In spite of great development in nanoparticle-based drug delivery systems(DDSs)for improved therapeutic efficacy,it remains challenging for effective delivery of chemotherapeutic drugs to targeted tumor cells.In this work,we report a triangle DNA origami as targeted DDS for cancer therapy.DNA origami shows excellent biocompatibility and stability in cell culture medium for 24 h.In addition,the DNA origami structures conjugated with multivalent aptamers enable for efficient delivery of anticancer drug doxorubicin(Dox)into targeted cancer cell due to their targeting function,reducing side effects associated with nonspecific distribution.Moreover,we also demonstrated that the multivalent aptamer-modified DNA origami loading Dox exhibits prominent therapeutic efficacy in vitro.Accordingly,this work provides a good paradigm for the development of DNA origami nanostructure-based targeted DDS for cancer therapy.     

Design of Degradable Click Delivery Systems

Click chemistry has had a significant impact in the field of materials science over the last 10 years, as it has enabled the design of new hybrid building blocks, leading to multifunctional and responsive materials. One key application for such materials is in the biomedical field, such as gene or drug delivery. However, to meet the functional requirements of such applications, tailored degradability of these materials under biological conditions is critical. There has been an increasing interest in combining click chemistry techniques with a range of degradable or responsive building blocks as well as investigating new or milder chemistries to design click delivery systems that are capable of physiologically relevant degradation. This Feature Article will cover some of the different approaches to synthesize degradable click delivery systems and their investigation for therapeutic release.

     

智能性药物释放体系

本文综述了智能性药物释放体系的进展,结合智能高聚物对化学及物理响应性聚合物为基础的体系,结合我们的工作对其自反馈释放及通-断特性进行了探讨。     

Synthesis and Characterization of Sterculia Gum Based pH Responsive Drug Delivery System for Use in Colon Cancer

The present study deals with the modification of sterculia gum to develop the novel colon specific delivery system for use in colon cancer. The sterculia and acrylic acid based hydrogels were synthesized and characterized with FTIR, SEMs, TGA and swelling behavior. Swelling studies of the hydrogels were carried out as a function of reaction parameters such as monomer concentration, initiator concentration, amount of sterculia gum and crosslinker concentration and nature of swelling mediums. Swelling kinetics of the hydrogels and in vitro release dynamics of anticancer model drug methotrexate from the hydrogels were studied to evaluate the swelling mechanism and drug release mechanism from the drug-loaded hydrogels. The values of diffusion exponent for the release of drug were 0.883, 0.910 and 0.787 in distilled water, pH 2.2 buffer and pH 7.4 buffer, respectively. The release of drug from the polymer matrix occurred through a non -Fickian type diffusion mechanism.     

Green Algae as a Drug Delivery System for the Controlled Release of Antibiotics

New strategies to efficiently treat bacterial infections are crucial to circumvent the increase of resistant strains and to mitigate side effects during treatment. Skin and soft tissue infections represent one of the areas suffering the most from these resistant strains. We developed a new drug delivery system composed of the green algae, Chlamydomonas reinhardtii, which is generally recognized as safe, to target specifically skin diseases. A two-step functionalization strategy was used to chemically modify the algae with the antibiotic vancomycin. Chlamydomonas reinhardtii was found to mask vancomycin and the insertion of a photocleavable linker was used for the release of the antibiotic. This living drug carrier was evaluated in presence of Bacillus subtilis and, only upon UVA1-mediated release, growth inhibition of bacteria was observed. These results represent one of the first examples of a living organism used as a drug delivery system for the release of an antibiotic by UVA1-irradiation.     

Stereocomplex Polylactide for Drug Delivery and Biomedical Applications: A Review

Polylactide (PLA) is among the most common biodegradable polymers, with applications in various fields, such as renewable and biomedical industries. PLA features poly(D-lactic acid) (PDLA) and poly(L-lactic acid) (PLLA) enantiomers, which form stereocomplex crystals through racemic blending. PLA emerged as a promising material owing to its sustainable, eco-friendly, and fully biodegradable properties. Nevertheless, PLA still has a low applicability for drug delivery as a carrier and scaffold. Stereocomplex PLA (sc-PLA) exhibits substantially improved mechanical and physical strength compared to the homopolymer, overcoming these limitations. Recently, numerous studies have reported the use of sc-PLA as a drug carrier through encapsulation of various drugs, proteins, and secondary molecules by various processes including micelle formation, self-assembly, emulsion, and inkjet printing. However, concerns such as low loading capacity, weak stability of hydrophilic contents, and non-sustainable release behavior remain. This review focuses on various strategies to overcome the current challenges of sc-PLA in drug delivery systems and biomedical applications in three critical fields, namely anti-cancer therapy, tissue engineering, and anti-microbial activity. Furthermore, the excellent potential of sc-PLA as a next-generation polymeric material is discussed.     

Advanced Drug Delivery Micro- and Nanosystems for Cardiovascular Diseases

Advanced drug delivery micro- and nanosystems have been widely explored due to their appealing specificity/selectivity, biodegradability, biocompatibility, and low toxicity. They can be applied for the targeted delivery of pharmaceuticals, with the benefits of good biocompatibility/stability, non-immunogenicity, large surface area, high drug loading capacity, and low leakage of drugs. Cardiovascular diseases, as one of the primary mortalities cause worldwide with significant impacts on the quality of patients’ life, comprise a variety of heart and circulatory system pathologies, such as peripheral vascular diseases, myocardial infarction, heart failure, and coronary artery diseases. Designing novel micro- and nanosystems with suitable targeting properties and smart release behaviors can help circumvent crucial challenges of the tolerability, low stability, high toxicity, and possible side- and off-target effects of conventional drug delivery routes. To overcome different challenging issues, namely physiological barriers, low efficiency of drugs, and possible adverse side effects, various biomaterials-mediated drug delivery systems have been formulated with reduced toxicity, improved pharmacokinetics, high bioavailability, sustained release behavior, and enhanced therapeutic efficacy for targeted therapy of cardiovascular diseases. Despite the existing drug delivery systems encompassing a variety of biomaterials for treating cardiovascular diseases, the number of formulations currently approved for clinical use is limited due to the regulatory and experimental obstacles. Herein, the most recent advancements in drug delivery micro- and nanosystems designed from different biomaterials for the treatment of cardiovascular diseases are deliberated, with a focus on the important challenges and future perspectives.     

A New Multiresponsive Drug Delivery System using Smart Nanogels

This paper addresses the synthesis and characterization of a novel temperature‐ and pH‐responsive nanogel system based on poly(vinylcaprolactam‐co‐2‐dimethylaminoethyl methacrylate) [P(VCL‐co‐DMAEMA)] by using a surfactant‐free emulsion polymerization procedure for the multiresponsive drug delivery of hydrophobic drugs. The effects of solvent, monomer, pH, and temperature were studied to tailor the average particle hydrodynamic diameters and the polydispersity index of the final particles. According to dynamic light‐scattering measurements, the obtained nanogels show a narrow particle‐size distribution and their hydrodynamic diameters can be varied from 81 to 368 nm. The nanogels display a re‐entrant phase‐transition state, and the equilibrium volume swelling ratio of the nanogels decreases drastically down to 47 °C and then increases up to 65 °C. In addition, the nanogels show pH‐dependent behavior. They exhibit a maximum size at pH 5.0. Rhodamine B (RhB) was chosen as a model compound for drug loading and release studies from P(VCL‐co‐DMAEMA) on the basis of particles in different phosphate buffer solutions at different temperatures. The temperature/pH‐dependent cumulative release and ultrasound‐enhanced pulsatile release properties were investigated for RhB‐loaded nanogels for long‐term and one‐shot delivery. The nanogels display efficient delivery for both long‐term and one‐shot delivery systems. We provide here a proof of concept for the novel use of multiresponsive nanogels having an overall size below 200 nm as a cargo system for hydrophobic drugs and for controlled release mediated by temperature/pH and ultrasound.     

Thermoresponsive,Hydrolytically Degradable Polymer Micelles Intended for Radionuclide Delivery

Novel polymer micelles, prepared by self‐assembling thermoresponsive poly(N‐isopropylacrylamide)‐graft‐poly[N‐(2‐hydroxypropyl)methacrylamide] copolymers with hydrolytically degradable N‐glycosylamine groups between the polymer blocks are proposed for delivery of diagnostic and therapeutic radionuclides into solid tumors. The micelles are formed by fast heating of an aqueous solution of the copolymer to 37 °C. They have a hydrodynamic diameter of 128 nm (measured using dynamic light scattering) and slowly degrade during incubation in aqueous buffer at pH = 7.4. Labeling with both ¹³¹I and ⁹⁰Y proceeds with high yields (>85%). The unlabeled polymers are not cytotoxic for any of the tested murine and human cell lines.

     

Investigation of Microemulsion System for Transdermal Drug Delivery of Amphotericin B

In order to solve the drawback of poor bioavailability by the oral route and infusion-related side effect for Amphotericin B(AmB), microemulsion vehicles composed of isopropyl myristate(IPM), Tween 80, isopropyl alcohol and water for transdermal delivery of AmB were designed. The pseudo-ternary phase diagrams were constructed by the H2O titration method and the structures of the microemulsion were determined by measuring electrical conducti-vities(σ). The diffusion studies of AmB microemulsion were performed via excised rabbit skin on a drug diffusion apparatus. To obtain a high solubization of AmB, three different methods were tested to incorporate AmB into mi-croemulsion. The result suggests adding AmB in the shape of NaOH solution to the O/W blank microemulsion over the phase inversion temperature(PIT) of the emulsifier obtains the maximum drug content(2.96 mg/mL). The pH value of the system could be adjusted to pH8.5 or pH<5.2, in this range AmB molecules converts from aqueous to the hydrophilic shell of the microemulsion droplets, drug precipitate is no more than 5%, and the formulations were corresponding to the characterizations of microemulsion. At pH 5.14, AmB microemulsion with Km 1:1, O/SC 1:9(mass ratio ofoil phase to surfactant/cosurfactant blend), water content 64.6%, drug content (2.93±0.08) mg/mL,showed the maximum permeation rate(3.255±0.64)μg·cm-2·h-1,which is stable for a long time.     

A New Drug Delivery System Based on Tauroursodeoxycholic Acid and PEDOT

Localized drug delivery represents one of the most challenging uses of systems based on conductive polymer films. Typically, anionic drugs are incorporated within conductive polymers through electrostatic interaction with the positively charged polymer. Following this approach, the synthetic glucocorticoid dexamethasone phosphate is often delivered from neural probes to reduce the inflammation of the surrounding tissue. In light of the recent literature on the neuroprotective and anti-inflammatory properties of tauroursodeoxycholic acid (TUDCA), for the first time, this natural bile acid was incorporated within poly(3,4-ethylenedioxythiophene) (PEDOT). The new material, PEDOT—TUDCA, efficiently promoted an electrochemically controlled delivery of the drug, while preserving optimal electrochemical properties. Moreover, the low cytotoxicity observed with viability assays, makes PEDOT–TUDCA a good candidate for prolonging the time span of chronic neural recording brain implants.     

过饱和度理论及过饱和药物递送系统

在药物研发领域,如何有效提高难溶性药物的溶解与吸收是一个极具挑战的难题。目前,过饱和药物递送系统(Supersaturating drug delivery systems,SDDS)利用药物溶液处于过饱和态的优势,可同时提高难溶性药物的表观溶解度与渗透性。本文对过饱和度的理论及其在药物研发领域中的实际应用进行了系统的综述,介绍了过饱和度的产生与维持、及其与药物吸收的关系,归纳了常用的SDDS技术,并对无定形固体分散体、共晶、无定形/共无定形产生过饱和进行重点阐述。