Synthesis and in vitro biological evaluation as antitumour drug carriers of folate‐targeted N‐isopropylacrylamide‐based nanohydrogels

Copolymeric nanohydrogels based on N‐isopropylacrylamide, N‐(pyridin‐4‐ylmethyl)acrylamide and tert‐butyl‐2‐acrylamidoethyl carbamate, synthesized by microemulsion polymerization, were characterized using Fourier transform infrared spectroscopy and their size (38–52 nm) determined using quasielastic light scattering. Folic acid was covalently attached to the nanohydrogels (1.40 ± 0.07 mmol g^?1). Tamoxifen (6.7 ± 0.2–7.3 ± 1.2 µg TMX mg^?1 nanohydrogel), a hydrophobic anticancer drug, and 5‐fluorouracil (7.7 ± 0.7–10.14 ± 1.75 µg 5‐FU mg^?1 nanohydrogel), a hydrophilic anticancer drug, were loaded into the nanohydrogels. Maximum in vitro TMX release (77–84% of loaded drug) depended on interactions of the drug with hydrophobic clusters of the nanogels; however, no nanogel/5‐FU interactions allowed total release of the loaded drug. The cytotoxicity of unloaded nanohydrogels in MCF7, T47D and HeLa cells was low. Cell uptake of nanogels without bound folic acid took place in the three cell types by unspecific internalization in a time‐dependent process. Cell uptake increased for folic acid‐targeted nanohydrogels in T47D and HeLa cells, which have folate receptors. The administration of 10 and 30 µmol L^?1 TMX by TMX‐loaded nanogels and 10 µmol L^?1 5‐FU by 5‐FU‐loaded nanogels was effective on the three cell types, and the best results were obtained for folic acid‐targeted nanohydrogels. Copyright © 2012 Society of Chemical Industry     

Quinone propionic acid‐based redox‐triggered polymer nanoparticles for drug delivery: Computational analysis and in vitro evaluation

Redox‐responsive polymers with pendant quinone propionic acid groups as a redox trigger were optimized by computational modeling to prepare efficient redox‐triggered polymer nanoparticles (NPs) for drug delivery. Lipophilicities at complete reduction of redox‐responsive polymers (<5000 Da) constructed with adipic acid and glutaric acid were remarkably reduced to range from ?6.29 to ?0.39 compared with nonreduced state (18.87–32.46), suggesting substantial polymer solubility reversal in water. Based on this hypothesis, redox‐responsive NPs were prepared from the synthesized polymers with paclitaxel as model cancer drug. The average size of paclitaxel‐loaded NPs was 249.8 nm and their reconstitutions were stable over eight weeks. In vitro drug release profiles demonstrated the NPs to release >80% of paclitaxel over 24 h at a simulated redox‐state compared with 26.5 to 41.2% release from the control. Cell viability studies revealed that the polymer was nontoxic and the NPs could release paclitaxel to suppress breast cancer cell growth. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40461.     

Preparation and in vitro drug‐release behavior of 5‐fluorouracil‐loaded poly(hydroxybutyrate‐co‐hydroxyhexanoate) nanoparticles and microparticles

Poly(3‐hydroxybutyrate‐co‐3‐hydroxyhexanoate) (PHBHHx) copolymeric microparticles (MPs) and nanoparticles (NPs) were prepared by the double‐emulsion solvent‐evaporation technique. 5‐Fluorouracil (5‐Fu), an anticancer drug, was entrapped in PHBHHx NPs and MPs. A variety of parameters, including the species and concentration of different surfactants, power and time of ultrasonication for particle dispersion, and organic/aqueous solution ratio, that affected the production of the 5‐Fu‐loaded PHBHHx NP and MP particles and the release of 5‐Fu were studied. The results show that the prepared NPs and MPs were spherical in shape and about 160 nm and 3 μm in size, respectively, when cetyltrimethyl ammonium bromide was used as the emulsifier. The drug‐loading content (DLC) varied from 3.53 to 8.03% for 5‐Fu‐loaded NPs and from 4.83 to 18.87% for 5‐Fu‐loaded MPs and depended on the different initial feeding amounts of 5‐Fu. The encapsulation efficiency decreased with increasing DLC. The in vitro drug‐release characteristics appeared to have two phases with an initial burst effect occurring within the first 8 h; this was more obvious for the particles with low DLCs. The NPs with high DLC (8.03%) had the slowest release rate, 49.6% of 5‐Fu within 24 h. Therefore, PHBHHx copolymeric NPs and MPs can possibly be applied as drug‐delivery carrier materials in the future. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Self‐aggregated nanoparticles of N‐dodecyl,N′‐glycidyl(chitosan) as pH‐responsive drug delivery systems for quercetin

In this study, pH‐responsive amphiphilic chitosan (CS) nanoparticles were used to encapsulate quercetin (QCT) for sustained release in cancer therapy. The novel CS derivatives were obtained by synthesis with 2,3‐epoxy‐1‐propanol, also known as glycidol, followed by acylation with dodecyl aldehyde. Characterization was performed by spectroscopic, viscosimetric, and size‐determination methods. Critical aggregation concentration, morphology, entrapment efficiency, drug release profile, cytotoxicity, and hemocompatibility studies were also carried out. The average size distribution of the self‐assembling nanoparticles measured by dynamic light scattering ranged from 140 to 300 nm. In vitro QCT release and Korsmeyer–Peppas model indicated that pH had a major role in drug release. Cytotoxicity assessments indicated that the nanoparticles were non‐cytotoxic. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay further revealed that QCT‐loaded nanoparticles could inhibit MCF‐7 cell growth. In vitro erythrocyte‐induced hemolysis indicated the good hemocompatibility of the nanoparticles. These results suggest that the synthesized copolymers might be potential carriers for hydrophobic drugs in cancer therapy. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45678.     

Preparation and characterization of poly‐DL‐lactide–poly(ethylene glycol) microspheres containing λDNA

Polylactide (PLA) and a block copolymer, poly‐DL ‐lactide–poly(ethylene glycol) (PELA) were synthesized by bulk ring‐opening polymerization initiated by stannous chloride. A linear DNA molecule, λDNA, was used as the model DNA. PLA, PELA, λDNA‐loaded PLA and PELA microspheres were prepared by the solvent‐extraction method based on the formation of multiple w₁/o/w₂ emulsion. The particle‐size distribution, surface morphology, and DNA loading characterized the microspheres. The mean diameter of λDNA‐loaded PELA microspheres was proved to be 3.5 μm. The integrity of the λDNA molecules, after preparing the microspheres, was determined by agarose gel electrophoresis. The result suggested that most of the λDNA molecules could retain their integrity after being encapsulated by PELA. The PELA microspheres could also prevent λDNA from being degraded by DNase. The in vitro degradation and release of PLA, PELA, and λDNA‐loaded PELA microspheres were carried out in a pH 7.4 buffer solution at 37°C. Quantitatively, evaluating the molecular weight reduction, the mass loss, the particle‐size changes, and the particle‐size distribution changes also monitored the degree of degradation. The release profile was assessed by measurement of the amount of λDNA present in the release medium at determined intervals. The degradation profiles of the PELA microspheres were quite different from those of the PLA microspheres. The introduction of the hydrophilic poly(ethylene glycol) domain in PLA and the presence of λDNA within the microspheres exhibit the apparent influence on the degradation and release profiles. A biphasic release profile was proved, that is, an initial burst release during the first days, then a gradual release. It was demonstrated that the PELA microspheres could be used potentially as a controlled release‐delivery system for λDNA. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 2557–2566, 2002     

Novel thermosensitive hydrogel composites based on poly(d,l‐lactide‐co‐glycolide) nanoparticles embedded in poly(n‐isopropyl acrylamide) with sustained drug‐release behavior

To reach sustained drug release, a new composite drug‐delivery system consisting of poly(d,l ‐lactide‐co‐glycolide) (PLGA) nanoparticles (NPs) embedded in thermosensitive poly(N‐isopropyl acrylamide) (PNIPAAm) hydrogels was developed. The PNIPAAm hydrogels were synthesized by free‐radical polymerization and were crosslinked with poly(ethylene glycol) diacrylate, and the PLGA NPs were prepared by a water‐in‐oil‐in‐water double‐emulsion solvent‐evaporation method. The release behavior of the composite hydrogels loaded with albumin–fluorescein isothiocyanate conjugate was studied and compared with that of the drug‐loaded neat hydrogel and PLGA NPs. The results indicate that we could best control the release rate of the drug by loading it to the PLGA NPs and then embedding the whole system in the PNIPAAm hydrogels. The developed composite hydrogel systems showed near zero‐order drug‐release kinetics along with a reduction or omission of initial burst release. The differential scanning calorimetry results reveal that the lower critical solution temperature of the developed composite systems remained almost unchanged (<1°C increase only). Such a characteristic indicated that the thermosensitivity of the PNIPAAm hydrogel was not distinctively affected by the addition of PLGA NPs. In conclusion, an approach was demonstrated for the successful preparation of a new hybrid hydrogel system having improved drug‐release behavior with retained thermosensitivity. The developed systems have enormous potential for many biotechnological applications. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40625.     

PLA–PEG‐grafted hollow magnetic silica microspheres as the carrier of iodinated contrast media

In this work, hollow magnetic silica microspheres (HMS) were synthesized by the template method, polyethylene glycol (PEG) and poly(lactic acid) (PLA)‐grafted hollow magnetic microspheres HMS@PLA–PEG were successfully prepared through ring‐opening polymerization method. Ioversol was loaded into HMS@PLA–PEG by physical coating, and the drug loading content was up to 39.4%. It also exhibited a slower and steady release than HMS and the cumulative release was up to 55.1% at physiological pH, which implied the PLA–PEG could prolong the circulation time. Meanwhile, to improve the efficiency of contrast, we have developed composite microspheres encapsulating superparamagnetic iron oxide (Fe₃O₄) as magnetic target for increasing the local concentration of the contrast media and expecting to put magnetic resonance imaging (MRI) and computed tomography (CT) technology together to apply in medical applications. Furthermore, the cytotoxicity assay in vitro was also investigated. The results revealed the ioversol‐loaded HMS@PLA–PEG exhibited low toxicity at a higher concentration, even it is up to 400 μg/mL. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44914.     

Preparation of new dendrimer‐like star‐shaped amphiphilic poly(ethylene glycol)–poly(ϵ‐caprolactone) copolymers for biocompatible and high‐efficiency curcumin delivery

Novel amphiphilic star‐shaped terpolymers comprised of hydrophobic poly(?‐caprolactone), pH‐sensitive polyaminoester block and hydrophilic poly(ethylene glycol) (M_n = 1100, 2000 g mol^?1) were synthesized using symmetric pentaerythritol as the core initiator for ring‐opening polymerization (ROP) reaction of ?‐caprolactone functionalized with amino ester dendrimer structure at all chain ends. Subsequently, a second ROP reaction was performed by means of four‐arm star‐shaped poly(?‐caprolactone) macromer with eight ‐OH end groups as the macro‐initiator followed by the attachment of a poly(ethylene glycol) block at the end of each chain via a macromolecular coupling reaction. The molecular structures were verified using Fourier transform infrared and ¹H NMR spectroscopies and gel permeation chromatography. The terpolymers easily formed core–shell structural nanoparticles as micelles in aqueous solution which enhanced drug solubility. The hydrodynamic diameter of these agglomerates was found to be 91–104 nm, as measured using dynamic light scattering. The hydrophobic anticancer drug curcumin was loaded effectively into the polymeric micelles. The drug‐loaded nanoparticles were characterized for drug loading content, encapsulation efficiency, drug–polymer interaction and in vitro drug release profiles. Drug release studies showed an initial burst followed by a sustained release of the entrapped drug over a period of 7days at pH = 7.4 and 5.5. The release behaviours from the obtained drug‐loaded nanoparticles indicated that the rate of drug release could be effectively controlled by pH value. Altogether, these results demonstrate that the designed nanoparticles have great potential as hydrophobic drug delivery carriers for cancer therapy. © 2015 Society of Chemical Industry     

Chitosan/alginate nanoparticles stabilized by poloxamer for the controlled release of 5‐fluorouracil

In this study, stable 5‐fluorouracil (5‐FU)‐loaded chitosan (CS)/alginate (Alg) nanoparticles (NPs) were prepared with poloxamer as a surfactant. The effects of the Alg concentration, CS/Alg weight ratio, and poloxamer concentration on the properties of the 5‐FU‐loaded CS/Alg NPs were studied. The results of dynamic light scattering and transmission electron microscopy indicated that stable 5‐FU‐loaded CS/Alg NPs of around 200 nm with low‐size polydispersities were achieved. Furthermore, the in vitro release of the 5‐FU‐loaded CS/Alg NPs was investigated in phosphate buffer solution at pH 7.4. The results show that the encapsulation efficiency of 5‐FU depended on the drug feeding amount (DFA), poloxamer concentration, Alg concentration, and CS concentration. However, the in vitro release rate of the 5‐FU‐loaded CS/Alg NPs was only related to the DFA, Alg concentration, and CS concentration and was independent of the poloxamer concentration. The time of 5‐FU release from the CS/Alg NPs could becontrolled to be sustained for more than 12 h. According to this study, CS/Alg NPs stabilized by poloxamer could serve as a suitable candidate for the controlled release of 5‐FU. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Micelles formed by self‐assembly of hyperbranched poly[(amine‐ester)‐co‐(D,L‐lactide)] (HPAE‐co‐PLA) copolymers for protein drug delivery

BACKGROUND: The aim of the work presented was to synthesize a series of amphiphilic hyperbranched poly[(amine‐ester)‐co‐(D ,L ‐lactide)] (HPAE‐co‐PLA) copolymers and study the formation of copolymeric micelles. These copolymeric micelle systems are expected to be potential candidates for applications in protein drug delivery. RESULTS: The chemical structures of the copolymers were confirmed by Fourier transform infrared spectroscopy, ¹³C NMR and thermogravimetric analysis. Fluorescence spectroscopy and dynamic light scattering confirmed the formation of copolymeric micelles of the HPAE‐co‐PLA copolymers. The maintenance of stability of bovine serum albumin (BSA) during release from micelles in vitro was also measured using circular dichroism and fluorescence spectrometry. CONCLUSION: Novel hyperbranched HPAE‐co‐PLA copolymers have been synthesized. Conjugation of PLA to HPAE was proved to be an available method for the preparation of micelles for protein delivery. The BSA‐loaded micelles showed enhanced encapsulation efficiency and the structural stability of BSA was retained during the release process. The hyperbranched polymeric micelles could be useful as drug carriers for protein drug delivery systems. Copyright © 2008 Society of Chemical Industry     

Development of antimicrobial‐loaded polyurethane films for drug‐eluting catheters

To prepare antibacterial, polymeric catheters for preventing catheter‐induced infections, sulfathiazole was loaded into polyurethane by solubilizing with solvents and the resultant films were cast. Fourier transform infrared spectroscopy confirmed the presence of sulfathiazole in the drug‐loaded polyurethane films. The thermal and mechanical properties of the films were assessed using differential scanning calorimetry and dynamic mechanical analysis. The drug‐loaded films were immersed in constantly stirred, deionized water at 37 °C for in vitro drug release study. The experimental data obtained from the in vitro drug release study were fit into mathematical models. Antibacterial efficiency of released sulfathiazole was evaluated by Escherichia coli growth inhibition test. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46467.     

Zein nanoparticle‐embedded electrospun PVA nanofibers as wound dressing for topical delivery of anti‐inflammatory diclofenac

Bioactive wound dressings from poly(vinyl alcohol) (PVA) and zein nanoparticles (NPs) loaded with diclofenac (DLF) were prepared successfully by the single jet electrospinning method. DLF‐loaded zein NPs with an average diameter of ～228 nm were prepared using anti‐solvent precipitation method. The formulation of zein:DLF 1:1 exhibited optimum encapsulation efficiency of 47.80%. The NPs were characterized by dynamic light scattering, zeta‐potential measurement, and differential scanning calorimetry. In vitro, drug release profiles of the DLF‐loaded zein NPs, and PVA–zein NPs were also studied within 120 h and showed the release efficiency of nearly 80% from zein NPs. A more controlled release of DLF was achieved by embedding the zein NPs in the PVA nanofibers. Fourier transform infrared spectroscopy was used to analyze possible interactions between different components of the fabricated dressings. The mechanical properties of the developed dressings were also evaluated using uniaxial tensile testing. Young's modulus (E) of the dressings decreased after inclusion of zein NPs within the PVA nanofibers. Moreover, fibroblast culturing experiments proved that the composite dressings supported better cell attachment and proliferation compared to PVA nanofibers, by exhibiting moderate hydrophilicity. The results suggested that the electrospun composite dressing of PVA nanofibers and zein NPs is a promising topical drug‐delivery system and have a great potential for wound healing application. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46643.     

PEGylated polylysine derived copolymers with reduction‐responsive side chains for anticancer drug delivery

Reduction‐responsive drug delivery systems have recently gained intense attention in intracellular delivery of anticancer drugs. In this study, we developed a PEGylated polypeptide, poly(ethylene glycol)‐block‐poly(?‐propargyloxycarbonyl‐l ‐lysine) (PEG₁₁₃‐b‐PPAL), as a novel clickable substrate for conjugation of reduction‐responsive side chains for antineoplastic drug delivery. PEG₁₁₃‐b‐PPAL was synthesized through ring‐opening polymerization of alkyne‐containing N‐carboxyanhydride monomers. A designed disulfide‐containing side chain was introduced onto the PEGylated polypeptide by click reaction. The obtained copolymer PEG₁₁₃‐b‐P(Lys‐DSA) formed micelles by self‐assembly, which exhibited reduction‐responsive behavior under the stimulus of 10 mmol L^–1 glutathione (GSH) in water. A small molecule intermediate, compound 2 , was used as a model to investigate the thiol reduction mechanism of PEG₁₁₃‐b‐P(Lys‐DSA) copolymers. The anticancer drug doxorubicin (DOX) was then loaded into the micelles with a drug loading content of 6.73 wt% and a loading efficiency of 40.3%. Both the blank and the drug‐loaded micelles (DOX‐loaded polylysine derived polymeric micelles (LMs/DOX)) adopted a spherical morphology, with average diameters of 48.0 ± 13.1 and 63.8 ± 20.0 nm, respectively. The in vitro drug release results indicated that DOX could be released faster from the micelles by the trigger of GSH in phosphate buffered saline. Confocal laser scanning microscopy and flow cytometer analysis further proved the intracellular delivery of DOX by LMs/DOX and their GSH‐sensitive release behavior. A 3‐(4,5‐dimethyl‐thiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide assay showed that the polymers exhibited negligible cytotoxicity towards normal L929 cells or cancer MCF‐7 cells with a treated concentration up to 1.0 mg mL^–1. In conclusion, our synthesized biocompatible and biodegradable PEGylated polypeptides hold great promise for intracellular antineoplastic drug delivery. © 2019 Society of Chemical Industry     

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 and release characteristics of dexamethasone acetate loaded organochlorine‐free poly(lactide‐co‐glycolide) nanoparticles

Dexamethasone‐loaded poly(lactide‐co‐glycolide) (PLGA) devices are commonly used as model systems for controlled release. In this study, PLGA nanoparticles containing dexamethasone acetate were prepared by a nanoprecipitation technique in the absence of organochlorine solvents and were characterized by their mean size, ζ potential, scanning electron microscopy, and differential scanning calorimetry to develop a controlled release system. The analytical method for the quantification of dexamethasone acetate by high‐performance liquid chromatography was validated. The results show that it was possible to prepare particles at a nanometric size because the average diameter of the drug‐loaded PLGA particles was 540 ± 4 nm with a polydispersity index of 0.07 ± 0.01 and a ζ potential of ?2.5 ± 0.3 mV. These values remained stable for at least 7 months. The drug encapsulation efficiency was 48%. In vitro tests showed that about 25% of the drug was released in 48 h. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41199.     

Surfactant chain length effects on nanoparticles of biodegradable polymers for targeted drug delivery

Folic acid‐conjugated nanoparticles (NPs) of biodegradable polymer poly(lactic‐co‐glycolic acid) (PLGA), which were emulsified by long‐chain D ‐α‐tocopheryl polyethylene glycol succinate (vitamin E TPGS or simply TPGS) for targeted delivery of anticancer drugs, are prepared. The NPs were characterized for their size and size distribution, surface morphology, surface charge, drug encapsulation efficiency, and surface chemistry. The cellular uptake and the cytotoxicity of the drug‐loaded PLGA NPs were assessed in vitro with MCF7 breast cancer cells in close comparison with the corresponding Short‐chain TPGS (TPGS2k)‐coated PLGA NPs and the original drug. The long‐chain TPGS 2000 (TPGS2k)‐emulsified PLGA NPs showed great advantages over the short‐chain TPGS 1000 (TPGS1k)‐emulsified and the nude PLGA NPs. The folic acid‐conjugated TPGS2k‐emulsified PLGA NPs showed significant advantages in cellular uptake and therapeutic effects in vitro. The IC₅₀ value showed 90.4% less than that of the original drug. © 2012 American Institute of Chemical Engineers AIChE J, 2012     

Polyurethane/doxorubicin nanoparticles based on electrostatic interactions as pH‐sensitive drug delivery carriers

In order to obtain a pH‐sensitive delivery carrier for doxorubicin (DOX), DOX‐loaded polyurethane (PU·DOX) nanoparticles were readily prepared in water by electrostatic interactions between amphiphilic polyurethane with carboxyl pendent groups (PU‐COOH) and doxorubicin hydrochloride (DOX·HCl). The structures of the products obtained were characterized by Fourier transform infrared spectroscopy, ¹H NMR spectroscopy, gel permeation chromatography, UV–visible spectroscopy, dynamic light scattering and transmission electron microscopy. The average hydrodynamic size of the PU·DOX nanoparticles was around 182 nm with negative surface charge (?1.1 mV) and a spherical or rodlike shape. PU·DOX nanoparticles had a higher drug‐loading content of 14.1 wt%. The in vitro drug release properties of PU·DOX nanoparticles were investigated at pH 4.0, 5.0 and 7.4, respectively. PU·DOX nanoparticles exhibited a good pH‐sensitive drug release property, but there was almost no release of DOX from PU·DOX nanoparticles at pH 7.4. The in vitro cellular uptake assay and the Cell Counting Kit‐8 assay demonstrated that PU·DOX nanoparticles had a higher level of cellular internalization and higher inhibitory effects on the proliferation of human breast cancer (MCF‐7) cells than pure DOX. The enhancement of the inhibition effects resulted from increasing apoptosis‐inducing effects on MCF‐7 cells, which was related to the enhancement of Bax expression and the reduction of Bcl‐2 expression confirmed by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay, real‐time polymerase chain reaction (PCR) assay and western blot assay. © 2018 Society of Chemical Industry     

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.     

Poly‐D,L‐lactide and levofloxacin‐blended beads: A sustained local releasing system to treat osteomyelitis

Osteomyelitis is the inflammation of bone which is treated by a high dose of antibiotics given intravenously for 4–6 weeks. However, at present locally administered antibiotic such as gentamicin poly (methyl methacrylate) (PMMA) bead is nonbiodegradable and a secondary surgery is often inevitable. This study described the biodegradable material poly‐D , L ‐lactide (PLA) with 80 kDa molecular weight that could be used as a potential antibiotic carrier for local drug release. PLA was first dissolved in tetrahydrofuran followed by blending with levofloxacin (LFX) in a physical way. The blend was then molded into beads. The optimized weight ratio between PLA and LFX was designated as 45 : 15. Glass transition temperature and surface ultramicrostructure of the beads were measured. In vitro tests of drug release and bacteriostasis demonstrated that the PLA–LFX beads released high concentrations of antibiotic for the period of time (i.e., 6 weeks), which is needed to treat bone infection. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Thermosensitive polymeric micelles based on the triblock copolymer poly(d,l‐lactide)‐b‐poly(N‐isopropyl acrylamide)‐b‐poly(d,l‐lactide) for controllable drug delivery

A thermosensitive amphiphilic triblock copolymer, poly(d,l ‐lactide) (PLA)‐b‐poly(N‐isopropyl acrylamide) (PNIPAAM)‐b‐PLA, was synthesized by the ring‐opening polymerization of d,l ‐lactide; the reaction was initiated from a dihydroxy‐terminated poly(N‐isopropyl acrylamide) homopolymer (HO‐PNIPAAM‐OH) created by radical polymerization. The molecular structure, thermosensitive characteristics, and micellization behavior of the obtained triblock copolymer were characterized with Fourier transform infrared spectroscopy, ¹H‐NMR, gel permeation chromatography, dynamic light scattering, and transmission electron microscopy. The obtained results indicate that the composition of PLA‐b‐PNIPAAM‐b‐PLA was in good agreement with what was preconceived. This copolymer could self‐assemble into spherical core–shell micelles (ca. 75–80 nm) in aqueous solution and exhibited a phase‐transition temperature around 26 °C. Furthermore, the drug‐delivery properties of the PLA‐b‐PNIPAAM‐b‐PLA micelles were investigated. The drug‐release test indicated that the synthesized PLA‐b‐PNIPAAM‐b‐PLA micelles could be used as nanocarriers of the anticancer drug adriamycin (ADR) to effectively control the release of the drug. The drug‐delivery properties of PLA‐b‐PNIPAAM‐b‐PLA showed obvious thermosensitive characteristics, and the release time of ADR could be extended to 50 h. This represents a significant improvement from previous PNIPAAM‐based drug‐delivery systems. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45304.