Synergistic effect and drug‐resistance relief of paclitaxel and cisplatin caused by Co‐delivery using polymeric micelles

Combination therapy of paclitaxel (PTX) and cisplatin has been used to treat several cancers in clinic practice, but often causes serious systemic toxicity. Co‐delivery of PTX and cisplatin by means of polymeric micelles can reduce the systemic toxicity, but often needs two carrier polymers because of the solubility difference between them. Therefore, a strategy is developed to co‐deliver both PTX and cisplatin with only one carrier polymer by encapsulating PTX in the core of a polymeric micelle and cross‐linking the micelle with cisplatin. The PTX and Pt contents in the micellar formulation M(PTX/Pt) were 10 and 14 wt %, respectively. In vitro cytotoxicity of M(PTX/Pt) was evaluated via 3‐(4,5‐dimethylthiazol‐2‐yl)?2,5‐diphenyltetrazolium bromide assay in comparison with PTX and its micelle M(PTX), cisplatin and its micelle M(Pt), and PTX/cisplatin combination towards human hepatocarcinoma (SMMC‐7721) cells and chemoresistant SMMC‐7721(SMMC‐7721R) cells. The M(PTX/Pt) exhibited a high synergistic effect in the inhibition of cell growth and proliferation of both SMMC‐7721 and SMMC‐7721R cells and showed reasonable drug‐resistance relief. The synergistic effect and resistance relief were further supported or explained by intracellular uptake measurement of dye‐labeled micelles and by the confocal laser scanning microscopy observation of SMMC‐7721 and SMMC‐7721R cells treated with various formulations. Therefore, M(PTX/Pt) micelles were expected to find potential application in cancer chemotherapy. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41440.     

Investigations on porous PLA composite scaffolds with amphiphilic block PLA‐b‐PEG to enhance the carrying property for hydrophilic drugs of excess dose

To address concern of the dispersion property of hydrophilic drugs of excess dose loaded in a hydrophobic poly(lactic acid) (PLA) matrix, this work developed a PLA and PLA‐b‐polyethylene glycol (PEG) composite scaffold ( ) and studied its carrier properties for aspirin as a model hydrophilic drug. The porous functional scaffolds were prepared from PLA and PLA‐b‐PEG solutions with the dose of 5, 10, and 15 wt % aspirin preloaded. The products and control samples of pure PLA with the same loading amount for comparison were characterized by scanning electron microscopy and X‐ray diffraction to examine the miscibility and porous structure. Rapid degradations in a strongly basic solution were performed to determine the actual loading amount and the encapsulation ratio. The in vitro release in phosphate buffer saline (PBS) at 37.5 °C indicated that the addition of amphiphilic block polymer may efficiently enhance the dispersion property and stabilize the release of hydrophilic drugs, especially with a high loading dose. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44489.     

Synthesis of a novel pH‐sensitive polyurethane–alginate blend with poly(ethylene terephthalate) waste for the oral delivery of protein

With the aim of using poly(ethylene terephthalate) (PET) waste for the synthesis of a value added product, we prepared polyurethane (PU) from bishydrohxyethylene terephthalate (BHET), a byproduct obtained from the glycolysis of PET. Biodegradable, water‐swelling PU was synthesized by the reaction of BHET, hexamethylene diisocyanate, and poly(ethylene glycol) (PEG). Both BHET and PU were characterized by Fourier transform infrared spectroscopy, and the formation of PU was further confirmed by NMR analysis. The swelling behavior of PU in water was examined in terms of the various molecular weights of PEG. Semi‐interpenetrating network beads of PU and sodium alginate were prepared with calcium chloride (CaCl₂) as a crosslinker to attain a pH sensitivity for successful oral protein/drug delivery. Bovine serum albumin (BSA) was used as a model protein. The pH‐responsive swelling behavior and protein (BSA) release kinetics in different pH media corresponding to the gastrointestinal tract (pH 1.2 and 7.4) were investigated. The degree of swelling in the case of the PU–alginate beads at pH 1.2 was found to be at a minimum, whereas the degree of swelling was significantly elevated (1080%) at pH 7.4. This substantiated the pH sensitivity of the polymeric beads with a minimum loss of encapsulated protein in the stomach and the almost complete release of encapsulated protein in the intestine. This revealed good opportunities for oral protein/drug delivery with a polymer derived from waste PET. Moreover, the fungal biodegradation study confirmed its compatibility with the ecological system. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40650.     

Preparation of bioactive glycosylated glial cell‐line derived neurotrophic factor‐loaded microspheres for medical applications

Poly (lactic‐co‐glycolic acid) (PLGA)‐coated gelatin microspheres containing glial cell‐line derived neurotrophic factor (GDNF) were developed by thermal gelation through a water‐in‐oil emulsion technique. Gelatin types (A and B) at four different pH levels were investigated for their influences on the morphology, the microsphere size, the zeta potential, and the swelling ability. The encapsulation of GDNF and the release characteristics of GDNF were also determined using enzyme‐linked immunosorbent assay (ELISA). The maximum cumulative released amounts of GDNF from the microspheres were increased from 50 to 90% after 4 d (based on the actual amount of the GDNF). Thus, the release of the GDNF contents in the microspheres depends on the amount of GDNF. Trigeminal ganglion cells (TGCs) were used to study the bioactivity of GDNF released from the microspheres, which was proven to retain its bioactivity in promoting the TGCs' neurite outgrowth. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40167.     

Fluorescent microspheres of poly(ethylene glycol)–poly(lactic acid)–fluorescein copolymers synthesized by Ugi four‐component condensation

Microparticles formed by poly(lactic acid) (PLA) and poly(ethylene glycol) (PEG) diblock copolymers containing fluorescein grafted to the polymer chain were synthesized by a Ugi four‐component condensation (UFCC) reaction. To synthesize these copolymers, lactide was first polymerized by a ring‐opening polymerization with alcohol initiators containing functional groups to give carboxyl‐ and aldehyde‐end‐functionalized PLA. Two different fluorescent block copolymers (FCPs) of PEG–PLA conjugated to fluorescein (FCP 1 and FCP 2) were then synthesized by UFCC; they gave yields in the range 65–75%. These copolymers were characterized well according their chemical structures and thermal properties, and we prepared fluorescent microspheres (FMSs) from them with the single emulsion–solvent evaporation method (FMS 1 and FMS 2). A new application of UFCC in the preparation of biomasked drug‐delivery systems is proposed. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 42994.     

Facile fabrication of double‐walled polymeric hollow spheres with independent temperature and pH dual‐responsiveness for synergetic drug delivery

A dual‐responsive double‐walled polymeric hollow sphere (PHS) serving as a candidate for synergetic drug delivery platform is prepared by a simple and green template polymerization in aqueous medium. The PHS, comprised of thermo‐responsive crosslinked poly(N‐isopropylacrylamide) (PNIPAM) as the inner shell and pH‐responsive crosslinked poly(methacrylic acid) (PMAAc) as the outer shell, is assembled through self‐removal of the thermo‐responsive template from a core‐triple shell structure by free radical polymerization with sequential addition of reactants. The discrete double‐shell structure renders the PHS independent temperature and pH‐controlled swelling/shrinking capability. Taking the advantage of two compartmentalized internal spaces (the core and the interlayer spaces) with independent temperature‐ and pH‐dependent behaviors, two model drugs representing the small molecule and the macromolecule are loaded in selective locations of the PHS. Two drugs show dramatically different release profiles according to environmental temperature and pH, due to the localization of drugs and the stimuli‐dependent property of its protective shells. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 44335.     

Chitosan/nanocellulose-based bionanocomposite films for controlled betamethasone and silver sulfadiazine delivery

Bionanocomposite films based on chitosan and nanocellulose (nanocrystals or nanofibrils) have gained considerable attention for biomedical applications, especially for wound dressings. However, the development of these films as controlled drug release dressings is still under-exploited. Therefore, this work aimed to design chitosan/nanocellulose-based bionanocomposite films, loaded by betamethasone or silver sulfadiazine, as functional dressings. The films were obtained by solvent casting and characterized by physicochemical, mechanical, barrier properties, in vitro drug release, and antimicrobial activity. The nanocellulose type, physical state, and content caused influence on the film's properties providing different physical, barrier, and drug release profiles. They are semi-occlusive and mechanically resistant; the drug release is controlled, and possesses antimicrobial activity. In conclusion, the developed biodegradable bionanocomposite films are promising as active dressings for controlled drug delivery in the wound site and have specific applications according to their features to treat inflamed and purulent wounds, non-infectious dry wounds, and infectious wounds.     

Zein‐based micro‐ and nano‐particles for drug and nutrient delivery: A review

Zein is the major storage protein from corn with strong hydrophobicity and unique solubility and has been considered as a versatile food biopolymer. Due to the special tertiary structures, zein can self‐assemble to form micro‐ and nano‐particles through liquid–liquid dispersion or solvent evaporation approaches. Zein‐based delivery systems have been particularly investigated for hydrophobic drugs and nutrients. Recently, increasing attention has been drawn to fabricate zein‐based advanced drug delivery systems for various applications. In this review, the molecular models of zein tertiary structure and possible mechanisms involved in zein self‐assembly micro‐ and nano‐particles are briefly introduced. Then, a state‐of‐the‐art introduction and discussion are given in terms of preparation, characterization, and application of zein‐based particles as delivery systems in the fields of food science, pharmaceutics, and biomedicine. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40696.     

Development of ionic and non‐ionic natural gum‐based bigels: Prospects for drug delivery application

Recently, much attention has been focused on the development of gel based formulations for controlled drug delivery applications. Herein, we report the effect of the ionic (gum acacia) and the non‐ionic (guar gum) gums on the properties of the bigels prepared with fluid‐filled organogels. The microscopic study suggested the presence of flocculated structure in guar gum bigel, whereas, a de‐flocculated structure was observed in gum acacia bigel. Infrared spectroscopy suggested the presence of polysaccharides in the bigels. The mechanical properties of the guar gum bigel were better than gum acacia bigel. The conductivity and the release properties suggested superior properties of gum acacia bigel. This indicated that the ionic nature of acacia bigel played a major role in controlled drug delivery, making it a potential bigel for desired pharmaceutical applications. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42561.     

Green fabrication of porous chitosan/graphene oxide composite xerogels for drug delivery

Porous chitosan (CS)/graphene oxide (GO) composite xerogels were prepared through a simple and “green” freeze‐drying method. Scanning electron microscopy, Fourier transform infrared spectrometry, powder X‐ray diffraction, and compressive strength measurements were performed to characterize the microstructures and mechanical properties of as‐prepared composite xerogels. The results show that the incorporation of GO resulted in an observable change in the porous structure and an obvious increase in the compressive strength. The abilities of the composite xerogels to absorb and slowly release an anticancer drug, doxorubicin hydrochloride (DOX), in particular, the influence of different GO contents, were investigated systematically. The porous CS/GO composite xerogels exhibited efficient DOX‐delivery ability, and both the adsorption and slow‐release abilities increased obviously with increasing GO content. Additionally, the best adsorption concentration of DOX was 0.2 mg/mL, and the cumulative release percentage of DOX from the xerogels at pH4 much higher than that at pH 7.4. Therefore, such porous CS/GO composite xerogels could be promising materials as postoperation implanting stents for the design of new anticancer drug‐release carriers. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2014 , 131, 40006.     

How to circumvent untoward drug crystallization during emulsion‐templated microencapsulation process

Unwanted drug crystals often form on the surface of PLGA microspheres or in an aqueous phase when a hydrophobic drug undergoes emulsion‐templated microencapsulation processes. In our study, over 70% of progesterone crystallizes in the aqueous phase when microencapsulation proceeds with a typical oil‐in‐water solvent evaporation process. During filtration employed for microsphere recovery, unentrapped drug crystals are collected alongside with progesterone‐containing microspheres. This phenomenon accompanies unfavorable consequences on the microsphere quality. In contrast, when microspheres are prepared with a new solvent extraction‐evaporation hybrid process, it is possible to completely avoid drug crystallization. Consequently, the new microencapsulation technique yields high drug encapsulation efficiencies of ≥ 90.8%, and the resultant microspheres show a homogeneous size distribution pattern. Also, the microsphere surface is free of drug crystals. For loading hydrophobic drugs into PLGA microspheres, the new microencapsulation process reported in this study has distinct advantages over commonly used emulsion‐templated solvent evaporation processes. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43768.     

Gastro‐resistant controlled release of OTC encapsulated in alginate/chitosan matrix coated with acryl‐EZE® MP in fluidized bed

A gastro‐resistant system of acryl‐EZE® MP coated alginate/chitosan microparticles was developed to improve the controlled release of oxytetracycline (OTC). Microparticles were obtained by complex coacervation and, thereafter, were coated using fluidized polymer dispersion with acryl‐EZE® MP solution. OTC distribution inside the microparticles was determined by multiphoton confocal microscopy, demonstrating the efficiency of encapsulation process. In vitro OTC release kinetic was performed in order to obtain the release profile in gastric and intestinal simulated fluids. A fast initial release, or burst effect, was observed with uncoated microparticles loaded with OTC in gastric conditions. When a 50% mass increase in acryl‐EZE® MP coating was achieved, OTC release in acidic medium was greatly reduced, resulting in the expected gastro‐resistant effect. Different mathematical models were applied to describe the drug diffusion across the polymer matrix. The Logistic model was the best tool to interpret the experimental data in most of the systems studied. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40444.     

Fabrication of galactosylated chitosan–5‐fluorouracil acetic acid based nanoparticles for controlled drug delivery

In this study, a novel type of macromolecular prodrug, N‐galactosylated chitosan (GC)?5‐fluorouracil acetic acid (FUA) conjugate based nanoparticles, was designed and synthesized as a carrier for hepatocellular carcinoma drug delivery. The GC–FUA nanoparticles were produced by an ionic crosslinking method based on the modified ionic gelation of tripolyphosphate with GC–FUA. The structure of the as‐prepared GC–FUA was characterized by Fourier transform infrared and ¹H‐NMR analyses. The average particle size of the GC–FUA nanoparticles was 160.1 nm, and their drug‐loading content was 21.22 ± 2.7% (n = 3). In comparison with that of the freshly prepared nanoparticles, this value became larger after 7 days because of the aggregation of the GC–FUA nanoparticles. An in vitro drug‐release study showed that the GC–FUA nanoparticles displayed a sustained‐release profile compared to 5‐fluorouracil‐loaded GC nanoparticles. All of the results suggest that the GC–FUA nanoparticles may have great potential for anti‐liver‐cancer applications. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42625.     

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.     

Microemulsion of erythromycine for transdermal drug delivery

The aim of this work was to prepare an erythromycin (EM) microemulsion (EM‐ microemulsion) for transdermal EM delivery using isotropic mixtures of oil and aqueous phases. The prepared EM‐microemulsion is a white dispersion, with a suitable viscosity for transdermal delivery. In stability experiments, the EM‐microemulsion showed no marked change in appearance for up to 3 weeks at 25°C. In accelerated stability experiments at 37 and 60°C, however, precipitated crystalline EM particles were observed in the EM‐microemulsion. Diffusion of EM into the skin exhibited a first order release profile. Fluorescein (FL)‐microemulsion penetrated to the dermis layer of skin. In conclusion, we confirmed that EM‐microemulsion could serve as an excellent transdermal carrier of EM. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Imprinted microspheres doped with carbon nanotubes as novel electroresponsive drug‐delivery systems

Novel molecularly imprinted polymers (MIPs) suitable for the electroresponsive release of diclofenac were synthesized by precipitation polymerization in the presence of carbon nanotubes (CNTs). Both conventional and electroresponsive imprinted polymers were synthesized with methacrylic acid as the functional monomer and ethylene glycol dimethacrylate as the crosslinker. Preliminary experiments were performed to fully characterize the conventional MIPs and composite materials in terms of their morphological properties, recognition behavior, and electric resistivity. In vitro release experiments were performed in aqueous media to elucidate the ability of the MIPs and spherical imprinted polymers doped with CNTs to release the loaded template in a sustained manner over time in comparison to the that of the corresponding nonimprinted materials. Furthermore, a 20‐V direct‐current voltage was applied through the releasing media to evaluate how the electric field influenced the drug release to demonstrate the suitability of the proposed macromolecular system as an electroresponsive drug‐delivery device. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 829‐834, 2013     

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.     

Synthesis and characterization of star‐shaped PLLA with sorbitol as core and its microspheres application in controlled drug release

The purpose of this study was to investigate the suitability of a six‐arm star‐shaped poly(l ‐lactide)s (s‐PLLA) as controlled drug carriers for hydrophobic drug molecules. First, s‐PLLA was synthesized by ring‐opening polymerization of l ‐lactide using sorbitol as initiator and stannous octoate as catalyst. The structure and molecular weight (M_w) of s‐PLLA was characterized with ¹H NMR, ¹³C NMR, and GPC. Second, rifampicin (RIF) used as a model drug was encapsulated within the microspheres of s‐PLLA via oil‐in‐water emulsion/solvent evaporation technique. The morphology, drug encapsulation efficiency (EE), and in vitro release behavior of the prepared microspheres were studied in details. Results indicated that the average diameters of s‐PLLA microspheres can be controlled between 8 and 20 µm by varying the copolymer's concentration or M_w . The EE of RIF was mainly determined by the concentration of s‐PLLA. The in vitro study showed that the burst release behavior can be depressed by increasing the M_w of the s‐PLLA. Present work suggests that the synthesized s‐PLLA could be used as a new material for drug delivery. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42213.