Chitosan and chitosan/β‐cyclodextrin microspheres as sustained‐release drug carriers

The main aim of this study was to compare two microspheres, chitosan (CTS) and CTS/β‐cyclodextrin (β‐CD), made by spray‐drying, as pulmonary sustained drug‐delivery carriers. Theophylline (TH) was used as a model drug. The characteristics of the microspheres and in vitro release were studied. The yield of CTS/β‐CD microspheres was 46.1%, which was higher than that of the CTS microspheres (36.5%). The drug loads of the CTS and CTS/β‐CD microspheres were 22.7 and 21.1%, respectively, whereas the encapsulation efficiencies were 90.7 and 91.4%, respectively. The distribution of 50% [(diameter) d (0.5)] of the CTS microspheres was below 6.49 μm and that of the CTS/β‐CD microspheres was below 4.90 μm. Scanning electron microscopy showed that both microspheres yielded a spherical shape with smooth or wrinkled surfaces. Fourier transform infrared spectroscopy demonstrated that the carbonyl group of TH formed hydrogen bonds with the amide group of CTS and the hydroxyl group of β‐CD. The swelling ability of the two microspheres was more than three times their weight, and their humidity rates attained equilibrium within 24 h. The ciliary beat movement times of CTS and CTS/β‐CD microspheres were 493.00 and 512.33 min, respectively, which indicated that the two microspheres effectively reduced the ciliotoxicity and possessed better adaptability. In vitro release of TH from CTS/β‐CD microspheres was slower than that from CTS microspheres at pH 6.8 and provided a sustained release of 72.0% within 12 h. The results suggest that CTS/β‐CD microspheres are a promising carrier for sustained release for pulmonary delivery. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 1183–1190, 2007     

In vitro evaluation of spray‐dried chitosan microspheres crosslinked with pyromellitic dianhydride for oral colon‐specific delivery of protein drugs

Chitosan microspheres have been prepared using a spray‐drying method, and crosslinked with pyromellitic dianhydride. The chemical structure of the modified chitosan was characterized by FTIR spectroscopy and solid state 13C NMR analysis. The particle size and morphology of the crosslinked chitosan were investigated. These microspheres were evaluated for colon‐specific delivery of bovine serum albumin (BSA) as a model protein drug. The results indicate that the drug was released as follows: 37.1 ± 2.8% after 2 h in SGF, 73.1 ± 4.8% after 8 h (2 h in SGF+ 6 h in SIF), and 80.9 ± 4.1% after 12 h in SCF. The effect of β‐glucosidase on the drug release was also examined. The encapsulation efficiency was decreased from 88.4 ± 3.1% to 62.8 ± 2.9%, with increasing BSA concentration. Loading capacity was significantly increased from 6.3 ± 0.3% to 41.8 ± 4.1% by increasing the initial BSA concentration. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40514.     

Multiscale modeling for surface composition of spray‐dried two‐component powders

Spray drying is a primary process for manufacturing various powder products. One of the most important properties of powders is the ability to get wet. Surface chemical composition critically influences this property. Furthermore, surface composition also influences the efficiency of production as it affects the stickiness of the powder. This work is an attempt to analyze the surface compositions of spray‐dried two‐component powders produced under various conditions using an innovative multiscale modeling approach. A molecular‐level geometrical interpretation is seamlessly coupled with a continuum diffusion model. The predictions are compared with the measurements done on the protein–lactose system using X‐ray photoelectron spectroscopy. Sample calculations for the system have demonstrated that the new approach helps reveal surface formation mechanisms much better than that explained with the monoscale continuum approach. This work provides a good basis for a fruitful area of study toward surface composition‐focused powder quality control that will have a positive impact in industries. © 2014 American Institute of Chemical Engineers AIChE J, 60: 2416–2427, 2014     

Surface modification of monodisperse‐crosslinked polymeric microspheres using a redox initiation system

The surface modification of monodisperse‐crosslinked polymeric microspheres was carried out by introducing hydroxyl groups on the surface and utilizing the redox initiation system. The emulsions of the second monomer mixture were swollen into the monodisperse PS seed particles. The hydroxyl groups were introduced by hydrolysis of the acetate groups on the surface of microspheres. Ceric ammonium sulfate in sulfuric acid solution was employed to graft the acrylic monomer onto the polymeric microspheres. The surface characteristics of the surface‐modified particles were confirmed by FTIR, SEM, and TGA measurements. From the FE‐TEM image, a uniform coating layer was confirmed on the surface of microsphere. In DSC analysis, only an exothermal peak appeared when high content of DVB was used in the seeded polymerization, while, T_gs emerged after hydrolysis and graft polymerization using the low content of DVB in the second monomer. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 1349–1356, 2006     

Fabrication and drug release properties of poly(5‐benzyloxy‐trimethylene‐co‐glycolide) microspheres

Poly(5‐benzyloxy‐trimethylene carbonate‐co‐glycolide) random copolymers were synthesized through the ring‐opening polymerization of 5‐benzyloxy‐trimethylene carbonate and glycolide (GA). The copolymers with different compositions, PBG‐1 with 17% GA units and PBG‐2 with 45% GA units, were obtained. Using these copolymers, microsphere drug delivery systems with submicron sizes were fabricated using an “ultrasonic assisted precipitation method.” The in‐vitro drug release from these microspheres was investigated. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Crystallization behavior of spray‐dried and freeze‐dried graphene oxide/poly(trimethylene terephthalate) composites

Two types of graphene oxide (GO) powders were prepared by freeze‐drying or spray‐drying method, and their composites with poly(trimethylene terephthalate) (PTT) were prepared by melt blending. The influence of GO powders' type and content on crystallization behavior of PTT was investigated by differential scanning calorimeter (DSC) and polarized optical microscopy (POM). DSC results indicated that the overall crystallization rate of PTT was accelerated by well‐dispersed GO material which acts as a heterogeneous nucleation agent, since the Avrami parameter obtained is near 3. On the contrary, large GO aggregates which is in the minority will hinder the nucleation. Interestingly, large and well‐defined PTT spherulites instead of tremendous stunted spherulites were observed from POM, which means only a small portion of GO powders was acted as nucleation agent. Meanwhile, GO powders had no effect on PTT spherulites growth rate. In addition, the band spacing of PTT spherulites became weaker and wider with increasing GO content. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40332.     

肺部给药用高分子多孔微球的制备及改性研究进展

肺部给药作为一种非入侵式的给药方式,在蛋白质、多肽类药物的给药研究中具有很大的发展潜力。高分子多孔微球是最适合肺部给药的药物载体之一,本文首先阐述了高分子多孔微球的几种传统制备方法,分析了这些制备方法在不同的条件下存在的优点及缺点。随后本文针对传统的高分子多孔微球制备条件难以单独控制,药物不能有效包封等问题,对近年来研究者们为了提高多孔微球的性能对其进行的物理化学改性进行了综述并提出了观点。最后对肺部给药用高分子多孔微球不同的制备方法的相互结合以及在生物医学领域的应用价值进行了展望。     

Liver‐targeting doxorubicin‐conjugated polymeric prodrug with pH‐triggered drug release profile

The aim of the research presented was to develop a potential liver‐targeting prolonged‐circulation polymeric prodrug of doxorubicin (Dox) with a pH‐triggered drug release profile. In particular, linear dendritic block copolymers composed of polyamidoamine dendrimer (PAMAM) and poly(ethylene glycol) (PEG; number‐average molecular weight of 2000 g mol^?1) with or without galactose (Gal) were synthesized. Dox was coupled to the copolymers via an acid‐labile hydrazone linker. These prodrugs, designated Gal‐PEG‐b‐PAMAM‐Dox_n and mPEG‐b‐PAMAM‐Dox_m, showed accelerated Dox release as the pH decreased from 8.0 to 5.6. Cytotoxicity of the prodrugs was lower than that of free Dox due to the gradual drug release nature. Compared to mPEG‐b‐PAMAM‐Dox_m, Gal‐PEG‐b‐PAMAM‐Dox_n showed rather high cytotoxicity against Bel‐7402, suggestive of its galactose receptor‐mediated enhanced tumor uptake. This galactose receptor‐mediated liver‐targeted profile was further confirmed by the prolonged retention time in hepatoma tissue monitored using magnetic resonance imaging. Gal‐PEG‐b‐PAMAM‐Dox_n showed better in vivo antitumor efficacy than free Dox, suggesting its great potential as a polymeric antitumor prodrug. Copyright © 2010 Society of Chemical Industry     

Effects of drug and polymer molecular weight on drug release from PLGA‐mPEG microspheres

This study investigated the effects of drug and polymer molecular weight on release kinetics from poly (g ‐co‐glycolic acid)‐methoxypoly(ethyleneglycol) (PLGA‐mPEG) microspheres. Bovine serum albumin (BSA, 66 kDa), lysozyme (LZ, 13.4 kDa), and vancomycin (VM, 1.45 kDa) were employed as the model drugs, and encapsulated in PLGA‐mPEG microspheres of different molecular weight. Release of macromolecular BSA was mainly dependent on diffusion of drug at/ near the surface of the matrix initially and dependent on degradation of matrix at later stages, while, the small drug of vancomycin seemed to depend totally on diffusion for the duration of the release study. The release behavior of lysozyme was similar to bovine serum albumin, except a shorter lag period. PLGA‐mPEG molecular weight also affected the release behavior of bovine serum albumin and lysozyme, but not obviously. PLGA‐mPEG microspheres in smaller molecular weight seemed to degrade more quickly to obtain a mass lose and matrix erosion, and thus, an accelerated release rate of bovine serum albumin and lysozyme. Vancomycin released much faster than bovine serum albumin and lysozyme, and exhibited no lag period, as it is thought to be diffusion‐controlled. Besides, vancomycin showed no difference in release behavior as PLGA‐mPEG molecular weight change. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41431.     

Chitosan hydrogel‐coated cotton fabric: Antibacterial,pH‐responsiveness,and physical properties

In this work, chitosan hydrogel has been synthesized and used to impart pH‐sensitivity and antimicrobial finish to cotton fabric. In order to enhance the incorporation rate of hydrogel, anionic, and cationic activation of the textile surface was applied and then compared. The antibacterial activity of the fabric was then studied. The results revealed an enhancement of the antibacterial activities of the modified fabrics against Escherichia coli, Listeria monocytogene, and Staphylococcus aureus bacteria's. The capacity of material to respond to pH change was studied and confirmed using contact angle method. The anionic fabric treated with hydrogel showed a better pH‐responsiveness. Scanning electron microscopic testing results has also confirmed that the deposition of hydrogel was clearly better with the anionic activation. The characteristics of breathability of the fabrics were analyzed. The results show that the moisture management behavior of the finished materials is significantly better than the control one. Although the permeability to air has reduced by 10%, the permeability to water vapor remained practically unchanged. Furthermore, the effects of the antibacterial finishing on the physical properties of the cotton fabrics were also investigated. It was established that the functionalized samples have changed structure parameters, thickness, air permeability, tensile strength, and resistance to wrinkles. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46645.     

Spray‐dried microspheres as a route to clay/polymer nanocomposites

A new strategy for the preparation of well‐dispersed clays in a polymer matrix by a spray‐drying method is presented. Scanning electron microscopy and transmission electron microscopy measurements show that the spray‐drying process produces clay/polymer microspheres in which the clay is trapped in a well‐dispersed state throughout the polymer matrix. The microspheres have been successfully extruded into clay/poly(methyl methacrylate) nanocomposite bulk structures without any perturbation of the well‐dispersed clay nanostructure in the original microspheres. Transmission electron microscopy and small‐angle X‐ray scattering show that the clay particles in the extruded materials range from single platelets to simple tactoids composed of a few stacked clay platelets, indicating an excellent degree of dispersion. The results show that sprayed microspheres are very good precursors for further processing such as extrusion or melt blending with other polymers for bulk nanocomposite fabrication. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Preparation of novel amphiphilic copolymer microspheres and their drug‐release and glucose‐sensitive properties

A novel amphiphilic copolymer was prepared by the copolymerization of N‐acryloyl‐3‐aminophenylboronic acid with β‐cyclodextrin containing maleic anhydride. The copolymer was fully characterized with ¹³C‐NMR, ¹H‐NMR, IR, and scanning electron microscopy. The self‐assembling mechanism of the copolymer in H₂O–CH₃OH cosolvents was studied. Gliclazide as a model drug was loaded inside the copolymer microspheres, and the drug‐release behavior of the microspheres was studied. The results of in vitro oscillating release tests indicated that the microspheres responded to glucose rapidly in 30 min, and the microspheres exhibited self‐regulated on–off release behavior four to six times in 6 h between the solution with 3 g/L glucose and the medium without glucose; this met the clinical requirements of multidrug delivery. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Synthesis and modification of epoxy‐ and hydroxy‐functional microspheres

This article describes the synthesis and surface modification of epoxy‐ and hydroxy‐functional polymeric microspheres. The functionalized microspheres were synthesized using aqueous and nonaqueous cationic suspension photopolymerizations using multifunctional silicon‐containing epoxy monomers with iodonium salt photoinitiators. Although generally solid microspheres were obtained using these techniques, macroporous spheres could be obtained though the use of porogens. Various rapid and facile acid‐ and base‐catalyzed ring‐opening addition reactions were performed on the epoxy‐functional microspheres. These reactions include the additions of mercaptans, acid chlorides, isocyanates, amines, sodium azide, water, and alcohols. Similar functionalization reactions were performed on the hydroxy‐functional microspheres. The particle size and size distribution were determined using scanning electron microscopy. Fourier transform infrared spectroscopy was used to monitor the functionalization reactions. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 97: 1574–1585, 2005     

Surface modification and physical properties of various UHMWPE‐fiber‐reinforced modified epoxy composites

Two surface modification methods—plasma surface treatment and chemical agent treatment—were used to investigate their effects on the surface properties of ultrahigh‐molecular‐weight polyethylene (UHMWPE) fibers. In the analyses, performed using electron spectroscopy for chemical analysis, changes in weight, and scanning electron microscope observations, demonstrated that the two fiber‐surface‐modified composites formed between UHMWPE fiber and epoxy matrix exhibited improved interfacial adhesion and slight improvements in tensile strengths, but notable decreases in elongation, relative to those properties of the composites reinforced with the untreated UHMWPE fibers. In addition, three kinds of epoxy resins—neat DGEBA, polyurethane‐crosslinked DGEBA, and BHHBP‐DGEBA—were used as resin matrices to examine the tensile and elongation properties of their UHMWPE fiber‐reinforced composites. From stress/strain measurements and scanning electron microscope observations, the resin matrix improved the tensile strength apparently, but did not affect the elongation. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 655–665, 2007     

Determination of mechanical properties of polymeric microspheres used in controlled drug delivery systems by nanoindentation

In this study, we synthesized poly (vinyl acetate-co-divinyl benzene) microspheres with various monomer/cross-linker contents for oral/topical sustained drug release applications and determined the micromechanical properties by nanoindentation. Compression elastic moduli of materials were calculated by using the limited depth of indentation according to Hertz elastic deformation model and presented as the histogram of multiple data. In terms of drug release practices, poly (VAc-co-DVB) microspheres with a high DVB content, especially in topical applications, are expected to carry drugs under mechanical stresses of less than 1.0 GPa.     

Rheological properties and drug release characteristics of pH‐responsive hydrogels

Rheological properties, blend compatibility, and gel‐forming capacity of carbopol 940 (CP‐940), sodium alginate (NaAlg), and guar gum (GG) have been studied. These matrices have been used in delivery of timolol maleate for ophthalmic applications. Aqueous solutions of CP‐940, NaAlg, and GG in concentrations between 0.1 and 1% (wt/vol) and their blends have been prepared. In situ gel forming polymeric solutions have shown an increase in viscosity upon exposure to specific pH, ions, and temperature of the eyeball. Blend miscibility was studied by calculating polymer–polymer interaction parameters using viscosity data. Rheological properties viz., torque, viscosity, shear stress, and shear rate were obtained using a Brookfield rheometer. Viscosities of polymer solutions were obtained by a Schott Gerate viscometer. Rheological data were analyzed using Bingham, Casson Standard, and Casson Chocolate equations. The hydrogels were subjected to ex vivo release studies on timolol maleate through the excised bovine cornea using a modified Franz diffusion cell. Results were compared with the conventional drug solution. The release could be extended when the drug is incorporated into hydrogel‐forming solution. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 2057–2064, 2004     

Influence of microstructure of lactone‐based triblock copolymers on drug release behavior of their microspheres

The current work focuses on the influence of microstructure of different lactone‐based triblock copolymers on drug delivery, where the middle segment was δ‐valerolactone or ?‐caprolactone and the terminal segment was d ,l ‐lactide or cis ‐lactide. Microspheres were fabricated from the triblocks using salicylic acid as the model drug. The microsphere formation and drug release were investigated by scanning electron microscopy, ultraviolet–visible spectroscopy, X‐ray diffraction, and thermogravimetry. The size of the microspheres ranged from 2 to 20 µm in diameter. The diffusion coefficient values showed that replacement of the middle segment, δ‐valerolactone with ?‐caprolactone, retarded the diffusion of the drug molecules. The diffusion coefficient was lowered when d ,l ‐lactide content was decreased in the triblock. Mathematical models were used to predict the drug release from the microspheres of different triblocks. The modeling study on drug release profiles revealed that the biodegradable nature of the triblock played a crucial role in determining the drug release kinetics. The diffusion and degradation reaction justified the drug release from microsphere. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134 , 45284.     

Tamoxifen‐loaded microspheres based on mixtures of poly(D,L‐lactide‐co‐glycolide) and poly(D,L‐lactide) polymers: Effect of polymeric composition on drug release and in vitro antitumoral activity

Mixtures of different bioerosionable polyesters were used to prepare microparticulated tamoxifen delivery systems to achieve anticancer effects in breast malignant cancer cells. Tamoxifen (TMX) was included into microspheres (MS) formulated via spray‐drying. Mixtures of poly(D ,L ‐lactide‐co‐glycolide) (PLGA) of different lactide/glycolide proportions (50 : 50 and 75 : 25) and poly(D ,L ‐lactic acid) (PLA) were used. The average diameter of the resultant TMX‐loaded microparticles was in the range 1.04 ± 0.51–1.55 ± 0.95 μm. The encapsulation efficiency of TMX was between 97.8% [48.9 ± 0.1 TMX (μg)/MS (mg)] and 69.6% [36.6 ± 0.1 TMX (μg)/MS (mg)] depending on the polymeric composition of the formulation. Drug burst effect was not observed. TMX was released from the polymeric matrices in a sustained release manner between 11 and 58 days depending on polymeric composition of microspheres. TMX‐loaded microspheres showed high efficacy in causing cell death in MCF7 breast malignant cancer cells. Thus, these TMX‐loaded PLGA‐based microspheres hold potential to treat breast malignant cancer cells. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Preparation of ethyl cellulose microcapsules containing perphenazine and polymeric perphenazine based on acryloyl chloride for physical and chemical studies of drug release control

The preparation of microcapsules containing perphenazine by solvent evaporation using ethyl cellulose is described. The microparticles are formed after solvent evaporation and polymer precipitation. The drug was dissolved in a polymer solution and emulsified into an aqueous phase to form microcapsules. To study the effects on particle size, encapsulation efficiency and morphology, three different molecular weights of ethyl cellulose (M_w=47000, 71000 and 99000) were used. Covalent bonding of drugs to polymers via hydrolytically or enzymatically cleavable covalent bond was achieved for sustained drug delivery. The release rate of perphenazine from these systems was investigated. © 1998 Society of Chemical Industry     

Processing and properties of polymeric nano‐composites

Polymeric nano‐composites are prepared by melt intercalation in this study. Nano‐clay is mixed with either a polymer or a polymer blend by twin‐screw extrusion. The clay‐spacing in the composites is measured by X‐ray diffraction (XRD). The morphology of the composites and its development during the extrusion process are observed by scanning electron microscopy (SEM). Melt viscosity and mechanical properties of the composites and the blends are also measured. It is found that the clay spacing in the composites is influenced greatly by the type of polymer used. The addition of the nano‐clay can greatly increase the viscosity of the polymer when there is a strong interaction between the polymer and the nano‐clay. It can also change the morphology and morphology development of nylon 6/PP blends. The mechanical test shows that the presence of 5–10 wt.% nano‐clay largely increases the elastic modulus of the composites and blends, while significantly decreases the impact strength. The water absorption of nylon 6 is decreased with the presence of nano‐clay. The effect of nano‐clay on polymers and polymer blends is also compared with Kaolin clay under the same experimental conditions.