可降解高分子纳米纤维药物控释系统的研究进展

可降解高分子药物控释系统通过对药物剂量的有效控制,能够降低药物的毒副作用,提高药物的稳定性和利用率。近年来,静电纺丝纳米纤维因其具有比表面积大等特点,作为新型药物控制释放载体受到研究者的广泛关注。本文综述了可降解高分子纳米纤维药物控释系统的研究进展,对可降解高分子纳米纤维的制备及其在药物控释方面的研究进行介绍,并讨论了影响可降解高分子纳米纤维药物释放的因素。     

Bioadhesive Nanoparticles for Local Drug Delivery

Local drug delivery is an effective strategy for achieving direct and instant therapeutic effects. Current clinical treatments have fallen short and are limited by traditional technologies. Bioadhesive nanoparticles (NPs), however, may be a promising carrier for optimized local drug delivery, offering prolonged drug retention time and steadily maintained therapeutic concentrations. In addition, the possibility of clinical applications of this platform are abundant, as most polymers used for bioadhesion are both biodegradable and biocompatible. This review highlights the major advances in the investigations of polymer-based bioadhesive nanoparticles and their innumerable applications in local drug delivery.     

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。     

Dual‐Crosslinked Human Serum Albumin‐Polymer Hydrogels for Affinity‐Based Drug Delivery

A dual‐crosslinked in situ gelling drug delivery scaffold based on dextran (DEX), thiolated serum albumin, and poly(ethylene glycol) (PEG) is presented. Dextran–vinyl sulfone conjugates with varied molecular weight and degrees of substitution are synthesized by controlling the reaction time and temperature with divinyl sulfone. Dextran–human serum albumin (sHSA) hydrogels are prepared using a thiol‐vinyl sulfone Michael addition reaction with thiolated albumin as the crosslinker. Poly(ethylene glycol) dithiol is added as a third component to the crosslinked dextran–human serum albumin hydrogel to facilitate additional crosslinking, and reduce gelation time, while modulating the physicochemical properties of the Dex–sHSA–PEG network. The onset of gelation of the modular three‐component dual‐crosslinked hydrogel network ranges from 45 min to 1.5 h depending on gel constituent concentrations and the gelation temperature (25 or 37 °C). All gels remain stable for over a 25 d period under physiological conditions. In vitro drug release assays show that dual‐crosslinked Dex–sHSA–PEG hydrogels can deliver doxorubicin in a sustained manner over 7 d. Finally, a Tetrazolium‐based assay shows the biocompatible nature of the Dex–sHSA–PEG hydrogels and capacity to deliver doxorubicin successfully to MCF‐7 breast cancer cells.     

Nucleoside‐Based Self‐Assembling Drugs for Localized Drug Delivery

We have synthesized a range of gelators based on the nucleoside analogues gemcitabine and lamivudine, characterizing representative gels from the series using rheology and transmission electron microscopy. Growth inhibition studies of gemcitabine derivatives confirmed the feasibility of these compounds as novel treatments, indicating the potential of nucleoside‐based gelators for localized drug delivery.     

Targeted Delivery of Drugs and Genes Using Polymer Nanocarriers for Cancer Therapy

Cancer is one of the primary causes of worldwide human deaths. Most cancer patients receive chemotherapy and radiotherapy, but these treatments are usually only partially efficacious and lead to a variety of serious side effects. Therefore, it is necessary to develop new therapeutic strategies. The emergence of nanotechnology has had a profound impact on general clinical treatment. The application of nanotechnology has facilitated the development of nano-drug delivery systems (NDDSs) that are highly tumor selective and allow for the slow release of active anticancer drugs. In recent years, vehicles such as liposomes, dendrimers and polymer nanomaterials have been considered promising carriers for tumor-specific drug delivery, reducing toxicity and improving biocompatibility. Among them, polymer nanoparticles (NPs) are one of the most innovative methods of non-invasive drug delivery. Here, we review the application of polymer NPs in drug delivery, gene therapy, and early diagnostics for cancer therapy.     

Thermoplastic Starch and Drug Delivery Capsules

The thermoplastics processing of natural hydrophilic polymers in the presence of water is a recent development with very wide possible applications. Eventually, oil-based polymer materials could be replaced in many applications by inexpensive, natural products from renewable resources. As with conventional thermoplastics, hydrophilic polymer melts may be processed by injection-moulding and extrusion. The present contribution focuses on the injection-moulding of potato starch. The basis of the processing is described. In addition, the rheological behaviour of the starch/water melts during processing is analysed quantitatively to give apparent melt viscosities. The mechanical properties of moulded starch materials and the drug delivery behaviour of starch capsules are discussed. © 1997 SCI.     

Synthesis and Drug‐Delivery Behavior of Chitosan‐Functionalized Graphene Oxide Hybrid Nanosheets

Chitosan‐functionalized graphene oxides (FGOCs) were successfully synthesized. FGOCs were found to significantly improve the solubility of the GO in aqueous acidic media. The presence of organic groups was confirmed by means of XPS and TGA. Restoration of the sp² carbon network and exfoliation of graphene sheets were confirmed by Raman spectroscopy, UV‐visible spectroscopy and WAXD. The SEM and AFM investigations of the resultant FGOCs showed that most of the graphene sheets were individual and few were layered. Controlled release behavior of Ibuprofen and 5‐fluorouracil was then investigated. We found that FGOCs are a promising new material for biological and medical applications.

     

A Dissolution‐Diffusion Model and Quantitative Analysis of Drug Controlled Release from Biodegradable Polymer Microspheres

Controlled release behaviours of nifedipine loaded poly (D,L‐lactide) (PLA) and poly(D,L‐lactide‐co‐glycolide) (PLGA) microspheres are investigated and modelled in this paper. Based on the integrated consideration of diffusion, finite dissolution rate, moving front of dissolution and size distribution of microspheres, a mathematic model is presented to quantitatively describe the drug release kinetics. The coupled partial differential equations are numerically solved. Dynamic concentration profiles of both dissolved and undissolved drug in the microspheres are analyzed. In comparison with the diffusion model and Higuchi model, the proposed dissolution‐diffusion model is characteristic of describing the whole release process without limitation of different dissolution rate or dissolubility. The diffusion coefficient and the dissolution rate constants are evaluated from measured release profiles. The effects of microstructures of polymer microspheres on release behaviours are related to parameters of the model. Based on the mathematical model and in vitro release data, intrinsic mass transfer mechanism is further investigated.     

Synthesis,Characterisation, and Evaluation of a Cross-Linked Disulphide Amide-Anhydride-Containing Polymer Based on Cysteine for Colonic Drug Delivery

The use of disulphide polymers, a low redox potential responsive delivery, is one strategy for targeting drugs to the colon so that they are specifically released there. The objective of this study was to synthesise a new cross-linked disulphide-containing polymer based on the amino acid cysteine as a colon drug delivery system and to evaluate the efficiency of the polymers for colon targeted drug delivery under the condition of a low redox potential. The disulphide cross-linked polymers were synthesised via air oxidation of 1,2-ethanedithiol and 3-mercapto-N-2-(3-mercaptopropionamide)-3-mercapto propionic anhydride (trithiol monomers) using different ratio combinations. Four types of polymers were synthesised: P10, P11, P151, and P15. All compounds synthesised were characterised by NMR, IR, LC-MS, CHNS analysis, Raman spectrometry, SEM-EDX, and elemental mapping. The synthesised polymers were evaluated in chemical reduction studies that were performed in zinc/acetic acid solution. The suitability of each polymer for use in colon-targeted drug delivery was investigated in vitro using simulated conditions. Chemical reduction studies showed that all polymers were reduced after 0.5–1.0 h, but different polymers had different thiol concentrations. The bacterial degradation studies showed that the polymers were biodegraded in the anaerobic colonic bacterial medium. Degradation was most pronounced for polymer P15. This result complements the general consensus that biodegradability depends on the swellability of polymers in an aqueous environment. Overall, these results suggest that the cross-linked disulphide-containing polymers described herein could be used as coatings for drugs delivered to the colon.     

Drug‐loaded polyurethane/clay nanocomposite nanofibers for topical drug‐delivery application

In this study, polyurethane/nanoclay nanocomposite nanofibrous webs were prepared by electrospinning. An antiseptic drug, chlorhexidine acetate (CA), was loaded onto montmorillonite clay and was then incorporated into polyurethane nanofibers. For comparison, the CA drug was loaded directly into the polyurethane solution dope used to electrospin the nanofibers. The emphasis was on investigating the effect of the drug loading into the nanoclay vis‐à‐vis direct drug loading on the drug‐release behavior of nanofibrous webs. The nanofibrous webs were also evaluated for other properties, such as moisture vapor transmission, porosity determination, contact angle measurement, and antibacterial activity, which are important for topical drug‐delivery application. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40230.     

Microwave‐Assisted Preparation of Hydrogel‐Forming Microneedle Arrays for Transdermal Drug Delivery Applications

A microwave (MW)‐assisted crosslinking process to prepare hydrogel‐forming microneedle (MN) arrays was evaluated. Conventionally, such MN arrays are prepared using processes that includes a thermal crosslinking step. Polymeric MN arrays were prepared using poly(methyl vinyl ether‐alt‐maleic acid) crosslinked by reaction with poly(ethylene glycol) over 24 h at 80 °C. Polymeric MN arrays were prepared to compare conventional process with the novel MW‐assisted crosslinking method. Infrared spectroscopy was used to evaluate the crosslinking degree, evaluating the area of the carbonyl peaks (2000–1500 cm^?1). It was shown that, by using the MW‐assisted process, MN with a similar crosslinking degree to those prepared conventionally can be obtained in only 45 min. The effects of the crosslinking process on the properties of these materials were also evaluated. For this purpose swelling kinetics, mechanical characterisation, and insertion studies were performed. The results suggest that MN arrays prepared using the MW assisted process had equivalent properties to those prepared conventionally but can be produced 30 times faster. Finally, an in vitro caffeine permeation across excised porcine skin was performed using conventional and MW‐prepared MN arrays. The release profiles obtained can be considered equivalent, delivering in both cases 3000–3500 μg of caffeine after 24 h.

     

A Comparison of Electric‐Field‐Driven and Pressure‐Driven Fiber Generation Methods for Drug Delivery

Polymeric fibers are prepared by using electric field driven fiber production technology—electrospinning and pressure driven fiber production technology—pressurized gyration. Fibers of four different polymers: polyvinylidene fluoride (PVDF), poly(methyl methacrylate (PMMA), poly(N‐isopropylacrylamide), and polyvinylpyridine (PVP), are spun by both techniques and differences are analyzed for their suitability as drug carriers. The diameters of electrospun fibers are larger in some cases (PVDF and PMMA), producing fibers with lower surface area. Pressurized gyration allows for a higher rate of fiber production. Additionally, drug‐loaded PVP fibers are prepared by using two poorly water‐soluble drugs (Amphotericin B and Itraconazole). In vitro dissolution studies show differences in release rate between the two types of fibers. Drug‐loaded gyrospun fibers release the drugs faster within 15 min compared to the drug‐loaded electrospun fibers. The findings suggest pressurized gyration is a promising and scalable approach to rapid fiber production for drug delivery when compared to electrospinning.     

Amphiphilic Interpenetrating Polymer Networks for the Oral Delivery of Chemotherapeutics

New interpenetrating polymer networks (IPNs) composed of hydrophilic, pH‐responsive poly(methacrylic‐grafted‐ethylene glycol), and hydrophobic poly(n‐butyl acrylate) were formed for the oral delivery of chemotherapeutics. These amphiphilic IPNs were synthesized to express variations in swelling and hydrophobic properties to try and develop an optimized material for the loading and release of doxorubicin, a hydrophobic chemotherapeutic. Release profiles modeling the gastrointestinal (GI) transit from the stomach to the small intestine were investigated. Mucoadhesion was determined using fresh porcine small intestine, polymer samples, and a tensile tester. The biocompatibility of the materials was assessed against Caco‐2 and HT29‐MTX cell models representing the GI tract and SW620 cells serving as a colon cancer cell model. © 2013 American Institute of Chemical Engineers AIChE J, 59: 1472–1478, 2013     

Characterization of Magnesium Orotate‐Loaded Chitosan Polymer Nanoparticles for a Drug Delivery System

The drug release properties of magnesium orotate (MgOr) encapsulated in the chitosan (CS) cavity and the complexation behavior between MgOr and CS were investigated. The MgOr‐loaded CS nanoparticles (MgOrCSNPs) were characterized by differential scanning calorimetry, Fourier transform infrared spectroscopy, X‐ray diffraction, transmission electron microscopy, and scanning electron microscopy with energy‐dispersive X‐ray spectroscopy. MgOr was successfully encapsulated into the CS cavity. Results with 3‐(4,5‐dimethylthiazol‐2‐yl)2,5‐diphenyl tetrazolium bromide indicated that MgOrCSNPs retained their cytotoxic activity against the liver cancer cell line (HepG2) and breast cancer cell line (MCF‐7), and low toxicity against the human cell line (3T3) and human retinal epithelial cell line (ARPE‐19).     

Folic‐Acid‐Targeted Self‐Assembling Supramolecular Carrier for Gene Delivery

A targeting gene carrier for cancer‐specific delivery was successfully developed through a “multilayer bricks‐mortar” strategy. The gene carrier was composed of adamantane‐functionalized folic acid (FA‐AD), an adamantane‐functionalized poly(ethylene glycol) derivative (PEG‐AD), and β‐cyclodextrin‐grafted low‐molecular‐weight branched polyethylenimine (PEI‐CD). Carriers produced by two different self‐assembly schemes, involving either precomplexation of the PEI‐CD with the FA‐AD and PEG‐AD before pDNA condensation (Method A) or pDNA condensation with the PEI‐CD prior to addition of the FA‐AD and PEG‐AD to engage host–guest complexation (Method B) were investigated for their ability to compact pDNA into nanoparticles. Cell viability studies show that the material produced by the Method A assembly scheme has lower cytotoxicity than branched PEI 25 kDa (PEI‐25KD) and that the transfection efficiency is maintained. These findings suggest that the gene carrier, based on multivalent host–guest interactions, could be an effective, targeted, and low‐toxicity carrier for delivering nucleic acid to target cells.     

Drug‐loaded microparticles prepared by the one‐step deposition of calcium carbonate/alginate onto cotton fabrics

Calcium carbonate (CaCO₃)/alginate inorganic–organic hybrid particles were synthesized and deposited on to the surface of cotton fabrics with a novel one‐step procedure. The effects of the Ca²⁺/CO₃^2?/alginate molar ratio on the cotton matrix were investigated. The optimization of the process resulted in a regular shaped hybrid microparticles, and scanning electron microscopy revealed that the particles were uniformly distributed on the surface of the fibers. Dynamic light scattering showed that the particles were about 2 μm in diameter. Moreover, transmission electron microscopy images demonstrated that the core–shell structure of the particles existed along with CaCO₃ evenly enfolded into the alginate layer. An X‐ray diffraction pattern displayed that the alginate/CaCO₃ hybrid microparticles were a mixture of calcite and vaterite crystal. Fourier transform infrared spectroscopy indicated that CaCO₃/alginate hybrid particles formed in situ were the only deposited materials. The thermogravimetric analysis curve indicated a certain mass ratio of the alginate and CaCO₃ in the hybrid particles. Furthermore, the drug‐loading and drug‐release properties of the hybrid microspheres were studied, and the results show that the water‐soluble diclofenac sodium could be effectively loaded in the hybrid microparticles and the drug release could be effectively sustained. Finally, both of the microparticles and modified fabrics had good cytocompatibility. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42618.     

Roles of Albumin‐Binding Proteins in Cancer Progression and Biomimetic Targeted Drug Delivery

Nutrient transporters have attracted significant attention for their promising application in biomimetic delivery. Due to the active consumption of nutrients, cancer cells generally overexpress nutrient transporters to meet their increased need for energy and materials. For example, albumin‐binding proteins (ABPs) are highly overexpressed in malignant cells, stromal cells, and tumor vessel endothelial cells responsible for albumin uptake. ABP (e.g., SPARC) is a promising target for tumor‐specific drug delivery, and albumin has been widely used as a biomimetic delivery carrier. Apart from the transportation function, ABPs are closely associated with neoplasia, invasion, and metastasis. Herein, a summary of the roles of ABP in cancer progression and the application of albumin‐based biomimetic tumor‐targeted delivery through the ABP pathway is presented.     

Design of Gelatin-Capped Plasmonic-Diatomite Nanoparticles with Enhanced Galunisertib Loading Capacity for Drug Delivery Applications

Inorganic diatomite nanoparticles (DNPs) have gained increasing interest as drug delivery systems due to their porous structure, long half-life, thermal and chemical stability. Gold nanoparticles (AuNPs) provide DNPs with intriguing optical features that can be engineered and optimized for sensing and drug delivery applications. In this work, we combine DNPs with gelatin stabilized AuNPs for the development of an optical platform for Galunisertib delivery. To improve the DNP loading capacity, the hybrid platform is capped with gelatin shells of increasing thicknesses. Here, for the first time, full optical modeling of the hybrid system is proposed to monitor both the gelatin generation, degradation, and consequent Galunisertib release by simple spectroscopic measurements. Indeed, the shell thickness is optically estimated as a function of the polymer concentration by exploiting the localized surface plasmon resonance shifts of AuNPs. We simultaneously prove the enhancement of the drug loading capacity of DNPs and that the theoretical modeling represents an efficient predictive tool to design polymer-coated nanocarriers.     

Quantum Dot‐Based Nanotools for Bioimaging,Diagnostics, and Drug Delivery

Quantum dots (QDs) are highly fluorescent nanocrystals with advanced photophysical and spectral properties: high brightness and stability against photobleaching accompanied by broad excitation and narrow emission spectra. Water‐soluble QDs functionalized with biomolecules, such as proteins, peptides, antibodies, and drugs, are used for biomedical applications. The advantages of QD‐based approaches to immuno‐histochemical analysis, single‐molecule tracking, and in vivo imaging (over traditional methods with organic dyes and fluorescent proteins) are explained. The unique spectral properties of QDs offer opportunities for designing systems for multiplexed analysis by multicolor imaging for the simultaneous detection of multiple targets. Conjugation of drug molecules with QDs or their incorporation into QD‐based drug‐delivery particles makes it possible to monitor real‐time drug tracking and carry out image‐guided therapy. Because of the tunability of their photophysical properties, QDs emitting in the near‐infrared have become an attractive tool for deep‐tissue mono‐ and multiphoton in vivo imaging. We review recent achievements in QD applications for bioimaging, targeting, and drug delivery, as well as challenges related to their toxicity and non‐biodegradability. Key and perspectives for further development of advanced QD‐based nanotools are addressed.