Preparation and characterization of three types of cefquinome-loaded microspheres

The polymers of poly (lactic-co-glycolic acid), gelatin, and ethyl cellulose were used to control the microscopic structure of microspheres prepared by spray drying. We investigated controlled release by varying material concentrations, sprayer inlet temperatures and air velocities, and optimized process parameters of yield, particle size, and distribution. Three types of polymeric microspheres with a mean particle size range of 13–25?µm were loaded with cefquinome and characterized. In vitro drug release studies determined that microspheres were the most suitable structures for controlling release due to their high entrapment capacities and release times greater than 24?h.     

一种两亲生物降解高分子-聚丙交酯-聚乙二醇嵌段共聚物的研究进展

PLA-PEG良好的生物相容和降解性能在生物医学领域受到了广泛关注，对其性能和应用已经有了深入的研究。就PLA-PEG这一类两亲生物降解高分子的合成、性能作一简介，并对其在组织工程，药物控释以及靶向载体等方面的应用和前景作一综述和展望。     

Biodegradable electrospun mat: Novel block copolymer of poly (p‐dioxanone‐co‐L‐lactide)‐block‐poly(ethylene glycol)

Ultrafine fibers of a laboratory‐synthesized new biodegradable poly(p‐dioxanone‐co‐L ‐lactide)‐block‐poly(ethylene glycol) copolymer were electrospun from solution and collected as a nonwoven mat. The structure and morphology of the electrospun membrane were investigated by scanning electron microscopy, differential scanning calorimetry (DSC), wide‐angle X‐ray diffraction (WAXD), and a mercury porosimeter. Solutions of the copolymer, ranging in the lactide fraction from 60 to 80 mol % in copolymer composition, were readily electrospun at room temperature from solutions up to 20 wt % in methylene chloride. We demonstrate the ability to control the fiber diameter of the copolymer as a function of solution concentration with dimethylformamide as a cosolvent. DSC and WAXD results showed the relatively poor crystallinity of the electrospun copolymer fiber. Electrospun copolymer membrane was applied for the hydrolytic degradation in phosphate buffer solution (pH = 7.5) at 37 °C. Preliminary results of the hydrolytic degradation demonstrated the degradation rate of the electrospun membrane was slower than that of the corresponding copolymers of cast film. © 2003 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 1955–1964, 2003     

Synthesis and properties of functional aliphatic polycarbonates

Two, functional, cyclic carbonate monomers, 5‐methyl‐5‐methoxycarbonyl‐1,3‐dioxan‐2‐one and 5‐methyl‐5‐ethoxy carbonyl‐1,3‐dioxan‐2‐one, were synthesized starting from 2,2‐bis(hydroxymethyl) propionic acid. The ring‐opening polymerization of the cyclic carbonate monomers in bulk with stannous 2‐ethylhexanoate as a catalyst under different conditions was examined. The results showed that the yield and molecular weight of polycarbonates were significantly influenced by the reaction conditions. The polycarbonates obtained were characterized by IR, ¹H NMR, and differential scanning calorimetry. Their molecular weight was measured by gel permeation chromatography. The in vitro biodegradation and controlled drug‐release properties of the polycarbonates were also investigated. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 4001–4006, 2003     

Effect of molecular weight and degree of deacetylation on controlled release of isoniazid from chitosan microspheres

Glutaraldehyde cross‐linked chitosan microspheres for controlled release of isoniazid were prepared using chitosan of different molecular weights (MWs) and degrees of deacetylation (DDAs). Chitosan microspheres were characterized for their size, hydrophobocity, degree of swelling and loading of isoniazid. Hydrophobicity of chitosan microspheres increased on increasing the degree of cross‐linking and MW of chitosan. Chitosan microspheres with high degree of deacetylation (DDA) (75 wt%), high MW chitosan (2227 kg mol^?1), and with 12 wt% concentration of glutaraldehyde showed optimum loading and release of isoniazid. The isoniazid from chitosan microspheres was released in two steps, i.e. burst (%R_B) and controlled (%R_C) steps. The microspheres with low MW chitosan (260 kg mol^?1) and low DDA (48 wt%) showed prominent burst release of isoniazid, but microspheres with high MW chitosan (2227 kg mol^?1) and high DDA (75 wt%) have released more isoniazid in a controlled manner (60 wt%) at 37°C in a solution of pH 5.0 ± 0.1. The burst step of drug release (%R_B) has followed first order kinetics, whereas controlled step of drug release (%R_C) followed zero order kinetics. The burst step of drug release was Fickian and controlled step was non‐Fickian in nature. The diffusion constant (D) for isoniazid release was influenced by the properties of chitosan and degree of cross‐linking. Copyright © 2007 John Wiley & Sons, Ltd.     

Biodegradable and antibacterial poly(azomethine‐urethane)‐chitosan hydrogels for potential drug delivery application

In this study, biodegradable and antibacterial poly(azomethine‐urethane) (PAMU)‐ and chitosan (CS)‐based hydrogels have been prepared for controlled drug delivery applications. Structural and morphological characterizations of the hydrogels were performed via Fourier transform‐infrared and scanning electron microscopy analyses. Thermal stability, hydrophilicity, swelling, mechanical, biodegradation, protein absorption properties, and drug delivery application of PAMU‐ and CS‐based hydrogels were also investigated. The swelling performance of the hydrogels was studied in acidic, neutral, and alkaline media. Swelling results showed that the hydrogels have higher swelling capacity in acidic and alkaline media than neutral medium. Biodegradation experiments of the hydrogels were also studied via hydrolytic and enzymatic experiments. The drug release property of the hydrogel was carried out using 5‐fluoro uracil (5‐FU), and 5‐FU release capacity of the hydrogels was found in the range from 40.10% to 58.40% after 3 days.     

Pinosylvin‐Based Polymers: Biodegradable Poly(Anhydride‐Esters) for Extended Release of Antibacterial Pinosylvin

Pinosylvin is a natural stilbenoid known to exhibit antibacterial bioactivity against foodborne bacteria. In this work, pinosylvin is chemically incorporated into a poly(anhydride‐ester) (PAE) backbone via melt‐condensation polymerization, and characterized with respect to its physicochemical and thermal properties. In vitro release studies demonstrate that pinosylvin‐based PAEs hydrolytically degrade over 40 d to release pinosylvin. Pseudo‐first order kinetic experiments on model compounds, butyric anhydride and 3‐butylstilbene ester, indicate that the anhydride linkages hydrolyze first, followed by the ester bonds to ultimately release pinosylvin. An antibacterial assay shows that the released pinosylvin exhibit bioactivity, while in vitro cytocompatibility studies demonstrate that the polymer is noncytotoxic toward fibroblasts. These preliminary findings suggest that the pinosylvin‐based PAEs can serve as food preservatives in food packaging materials by safely providing antibacterial bioactivity over extended time periods.

     

The effects of melt annealing and counterpart's molecular weight on the thermal properties and phase morphology of poly(L‐lactide)‐based blends

The thermal properties and phase morphology of poly(L ‐lactide) (PLLA)‐based blends have been studied. Two poly(ethylene glycol)s (PEGs) with molecular weight (MW) of about 1,500 (1.5k) g/mol and 2,000,000 (2M) g/mol, respectively, were used as counterparts. The blends were annealed at a preselected temperature of 200 °C for either 2 min or 30 min before the characterizations. Both PEGs were determined to enhance the crystallizability of PLLA. After a 2‐min process of annealing, the PEG(1.5k)'s crystallization efficiency on PLLA has been noted to increase with the increase of its content. Conversely, PEG(2M)'s crystallization efficiency declined with the increase of its content. Extending the annealing time has evidently changed the PEGs' crystallization effect on PLLA. Moreover, the PEG(1.5k) has, to a greater extent, brought about the depression of PLLA's melting temperature by increasing its content, and this depression increased with the annealing time. The blends exhibited lower thermal stability than those of the parent components, particularly for the PEG(1.5k)‐included system with a higher PEG content. Regardless of the annealing time, the PEG(1.5k)‐included blends have shown homogeneous melt morphology under light microscope, whereas the PEG(2M)‐included blends have displayed phase‐separated melt morphology. In addition to the composition, PEG's MW and annealing time influence the crystalline morphology of the blends. The ringed PLLA spherulites have appeared mostly in the 2‐min annealed PEG(1.5k)‐included blends. © 2009 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 47: 1497–1510, 2009     

Novel ‘Nano in Nano’ Composites for Sustained Drug Delivery: Biodegradable Nanoparticles Encapsulated into Nanofiber Non‐Wovens

Novel ‘nano in nano’ composites consisting of biodegradable polymer nanoparticles incorporated into polymer nanofibers may efficiently modulate drug delivery. This is shown here using a combination of model compound‐loaded biodegradable nanoparticles encapsulated in electrospun fibers. The dye coumarin 6 is used as model compound for a drug in order to simulate drug release from loaded poly(lactide‐co‐glycolide) nanoparticles. Dye release from the nanoparticles occurs immediately in aqueous solution. Dye‐loaded nanoparticles which are encapsulated by electrospun polymer nanofibers display a significantly retarded release.

     

基于改性多糖交联的生物可降解水凝胶的合成及其释药性

在4-二甲氨基吡啶(DMAP)的催化下,天然高分子海带多糖(Lam)与甲基丙烯酸缩水甘油酯(GMA)发生亲核取代反应,制备出一种新型水溶性生物可降解交联剂——甲基丙烯酸缩水甘油酯接枝海带多糖(Lam-GMA)。以Lam-GMA为交联剂,与丙烯酰胺(AM)单体共聚制备水凝胶。在生理条件与脂肪酶的作用下,对凝胶的溶胀特性和降解行为进行研究。以牛血清白蛋白(BSA)为模型高分子药物,包埋在水凝胶中,研究其降解释药行为。结果表明,GMA接枝到Lam链的反应转化率很高,并且接枝率可控;交联剂用量越大,水凝胶降解所需时间越长;随着水凝胶的降解BSA缓慢释放。     

Ordered and Kinetically Discrete Sequential Protein Release from Biodegradable Thin Films

Multidrug regimens can sometimes treat recalcitrant diseases when single‐drug therapies fail. Recapitulating complex multidrug administration from controlled release films for localized delivery remains challenging because their release kinetics are frequently intertwined, and an initial burst release of each drug is usually uncontrollable. Kinetic control over protein release is demonstrated by cross‐linking layer‐by‐layer films during the assembly process. We used biodegradable and naturally derived components and relied on copper‐free click chemistry for bioorthogonal covalent cross‐links throughout the film that entrap but do not modify the embedded protein. We found that this strategy restricted the interdiffusion of protein while maintaining its activity. By depositing a barrier layer and a second protein‐containing layer atop this construct, we generated well‐defined sequential protein release with minimal overlap that follows their spatial distribution within the film.     

Biodegradable poly(trimethylene carbonate‐b‐(L‐lactide‐ran‐glycolide)) terpolymers with tailored molecular structure and advanced performance

The macroinitiator of poly(1,3‐trimethylene carbonate) (PTMC) with number‐average molecular weight ( ) of 9.6 × 10³ g mol⁻¹ was synthesized by ring‐opening polymerization at 120°C. Then, the novel terpolymer P(TMC‐b‐(LLA‐ran‐GA)) consisting of PTMC homopolymer segment attached with various monomer molar ratios of L‐lactide (LLA) and glycolide (GA) random copolymerization block was prepared with about 5.0 × 10⁴ g mol⁻¹ by ring‐opening polymerization in bulk at 140°C. The tailored molecular structures of P(TMC‐b‐(LLA‐ran‐GA)) were characterized by ¹H nuclear magnetic resonance, ¹³C NMR, FTIR, and gel permeation chromatography, and chain microstructure analysis was performed in detail with ¹³C NMR spectroscopy. The effect of GA units on the thermal and crystallization behaviors, mechanical properties, as well as biodegradability of terpolymers was investigated by differential scanning calorimetry, wide‐angle X‐ray diffraction, stress‐strain measurements, and in vitro tests in comparison with corresponding poly(trimethylene carbonate‐block‐L‐lactide) copolymer P(TMC‐b‐LLA). The results show that amorphous PTMC segments have a significant effect on condensed state behavior of the terpolymers, and the incorporation of GA units strongly decreases the crystallinity and crystallization ability of LLA segment within terpolymers because of more random LLA‐GA sequence and shorter average LLA block length. Meanwhile, the toughness of materials is greatly improved, and in vitro degradation is also accelerated. Peripheral vascular stents were 3D printed for the first time and met the requirements for application. The results show totally biodegradable terpolymers with unique molecular structure, and modifiable properties are promising new biomaterials with advanced performance for biomedical application.     

Biodegradable amphiphilic block copolymers containing functionalized PEO blocks:Controlled synthesis and biomedical potentials

A series of controllable amphiphilic block copolymers composed of poly(ethylene oxide)(PEO) as the hydrophilic block and poly(ε-caprolactone)(PCL) as the hydrophobic block with the amino terminal group at the end of the PEO chain(PCL-b-PEO-NH2) were synthesized.Based on the further reaction of reactive amino groups,diblock copolymers with functional carboxyl groups(PCL-b-PEO-COOH) and functional compounds RGD(PCL-b-PEO-RGD) as well as the triblock copolymers with thermosensitive PNIPAAm blocks(PCL-b-PEO-b-P...     

嵌段共聚物核交联胶束的制备与载药性能研究

在DMAP的催化和DIPC的作用下,丙烯酸的双键被引入聚乙二醇-聚己内酯嵌段共聚物的疏水链段上,制备胶束过程中使用过硫酸铵催化位于胶束内核部分的双键交联,得到的核交联胶束。在包载甲氨喋呤释放过程中,核交联胶束的累积释放率明显比非核交联胶束的小,具有良好的缓释效果。     

Superparamagnetic pH‐sensitive multilayer hybrid hollow microspheres for targeted controlled release

The superparamagnetic multilayer hybrid hollow microspheres have been fabricated using the layer‐by‐layer assembly technique by the electrostatic interaction between the polyelectrolyte cation chitosan (CS) and the hybrid anion citrate modified ferroferric oxide nanoparticles (Fe₃O₄‐CA) onto the sacrificial polystyrene sulfonate microspheres templates after etching the templates by dialysis. The saturation magnetization and magnetite contents of the superparamagnetic multilayer hybrid hollow microspheres were 32.46 emu/g and 51.3%, respectively. The hybrid hollow microspheres showed pH‐sensitive characteristics. The adsorption and release of the basic dye (methylene blue) were applied to investigate the interaction between the amino groups of CS and the carboxyl groups of the Fe₃O₄‐CA nanoparticles in different pH media. The superparamagnetic pH‐sensitive multilayer hybrid hollow microspheres are expected to be used for the targeted controlled release of drugs or in diagnostics. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3135–3144, 2010     

PEG-PLA block copolymer as potential drug carrier: preparation and characterization

Diblock and multiblock copolymers composed of a poly(D,L-lactide) (PLA) or poly(trimethylene carbonate) (PTMC) core with a hydrophilic chain of poly(ethylene glycol) (PEG) were prepared. These copolymers, in which the core is connected to PEG through a polyfunctional molecule such as citric, mucic, or tartaric acid, may be used to form nanoparticles for drug delivery applications. Branched copolymers were prepared by direct amidation between the polyfunctional acid and methoxy PEGamine, followed by ring-opening polymerization of lactide or trimethyl carbonate to form the PLA and PTMC block copolymers. In addition, a complex multiblock copolymer of biotin-PEG-poly[lactic-co-(glycolic acid)] (PLGA) for application in an avidin-biotin system was prepared for possible design of nanospheres with targeting properties. Studies of drug release from polymeric systems containing multiblock copolymers and studies of polymer degradation were also performed.     

Biodegradable hyaluronic acid/n-carboxyethyl chitosan/protein ternary complexes as implantable carriers for controlled protein release

An ampholytic N-carboxyethyl chitosan (CEC), with various isoelectric points (IPs), was synthesized by grafting acrylic acid on chitosan utilizing Michael's reaction. Compared to native chitosan, CEC has enhanced water solubility and dramatically accelerated enzymatic degradation; the rate of degradation is proportional to the degree of substitution (DS). The results from turbidimetric titration and fluorescence studies revealed that CEC formed complexes with either hyaluronic acid (HA) or bovine serum albumin (BSA) within a certain pH range. The HA/CEC/BSA ternary complexes could be prepared by colloid titration with quantitative yield and BSA entrapment. The rate of BSA release from the complexes was affected by pH, ionic strength, DS of CEC, and the molecular weight (MW) of HA. The endurance of BSA release from the complexes could be extended up to 20 d by formulating them with high-MW HA and CEC with low DS.BSA release profiles from HA/CEC-2/BSA complexes.     

Effect of Silk Protein Processing on Drug Delivery from Silk Films

Sericin removal from the core fibroin protein of silkworm silk is a critical first step in the use of silk for biomaterial‐related applications, but degumming can affect silk biomaterial properties, including molecular weight, viscosity, diffusivity and degradation behavior. Increasing the degumming time (10, 30, 60, and 90 min) decreases the average molecular weight of silk protein in solution, silk solution viscosity, and silk film glass‐transition temperature, and increases the rate of degradation of a silk film by protease. Model compounds spanning a range of physical‐chemical properties generally show an inverse relationship between degumming time and release rate through a varied degumming time silk coating. Degumming provides a useful control point to manipulate silk's material properties.

     

Effect of PLGA block molecular weight on gelling temperature of PLGA‐PEG‐PLGA thermoresponsive copolymers

Thermoresponsive, biodegradable polymeric hydrogel networks are used widely in medicinal applications. Poly(d ,l ‐lactic acid‐co‐glycolic acid)‐b‐poly(ethylene glycol)‐b‐poly(d ,l ‐lactic acid‐co‐glycolic acid) (PLGA‐PEG‐PLGA) triblock copolymers exhibit a sol–gel transition upon heating. The effect of PLGA block and PEG chain molecular weights (MWs) on the gelling temperature of polymer aqueous solution (20% w/w) is described. All polymer solutions convert into a hard gel within 2 °C of the gelling temperature. The release properties of the gels were displayed using paracetamol as a representative drug. A linear relation is described between the gelling temperature and PLGA block MW. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 35–39