Preparation and evaluation of chitosan/β‐cyclodextrin magnetic nanoparticles as a photodegradable and hydrophobic drug delivery carrier

In this study, novel tumor targeting nanocarriers comprised of chitosan (CS)/β‐cyclodextrin (β‐CD) magnetic nanoparticles were prepared to improve the photodegradable stability and bioavailability of hydrophobic drug. Resveratrol (Res) with photodegradable and hydrophobic properties was selected as a model drug. The photodegradation rate of Res in Fe₃O₄ nanoparticles solution was 7.8 times lower than that in the ethanol solution_. In addition, the value of the saturation magnetization of CS/β‐CD nanoparticles was found to be 19.56 emu/g with characteristic of superparamagnetism. Approximately 90% Res was entrapped into the CS/β‐CD magnetic nanoparticles with the size distribution ranging from 200 to 359 nm, and the nanoparticles were spherical in shape with high zeta potentials. Furthermore, the formation of CS/β‐CD nanoparticles showed a sustained release in vitro. These results indicated that the obtained CS/β‐CD magnetic nanoparticles were a promising magnetic targeting carrier for photodegradable and hydrophobic drugs. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45076.     

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     

Synthesis and characterization of grafting β‐cyclodextrin with chitosan

Two new adsorbents [β‐cyclodextrin–chitosan (β‐CD–CTS) and β‐cyclodextrin‐6–chitosan (β‐CD‐6‐CTS)] were synthesized by the reaction of β‐cyclodextrin (β‐CD) with epoxy‐activated chitosan (CTS) and the sulfonation of the C‐6 hydroxyl group of β‐cyclodextrin with CTS, respectively. Their structures were confirmed by IR spectral analysis and X‐ray diffraction analysis, and their apparent amount of grafting was determined by ultraviolet spectroscopy. The adsorption properties of β‐CD‐CTS and β‐CD‐6‐CTS for p‐dihydroxybenzene were studied. The experimental results showed that the two new adsorbents exerted adsorption on the carefully chosen target. The highest saturated capacity of p‐dihydroxybenzene of β‐CD‐CTS and β‐CD‐6‐CTS were 51.68 and 46.41 mg/g, respectively. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 860–864, 2004     

Preparation and characterization of a temperature‐sensitive nonwoven poly(propylene) with increased affinity for guest molecules

A temperature‐sensitive hydrogel with the capability of inclusion complex formation with guest molecules was successfully grafted onto the surface of nonwoven polypropylene (nonwoven PP). This was carried out by the use of N‐isopropylacrylamide monomer and a modified cyclodextrin (acrylamidomethyl‐β‐cyclodextrin (β‐CD‐NMA)). Fourier‐transform infra red (FT‐IR) and elemental analyses confirmed the presence of poly(N‐isopropylacrylamide) (PNIPAAm) and β‐CD‐NMA components on the surface of the textile. Equilibrium swelling ratio measurements showed that the grafted hydrogel maintained its temperature‐sensitive property compared to a nongrafted hydrogel. The effect of β‐CD‐NMA and crosslink agent concentrations on the grafting yield was studied. The β‐CD‐NMA content into the PNIPPAM‐ β‐CD‐NMA grafted nonwoven PP (PNIPAAm‐β‐CD‐NMA‐PP) was estimated by FT‐IR through a new procedure. The estimated amounts of β‐CD‐NMA in PNIPAAm‐β‐CD‐NMA‐PP were determined to be 0.9, 1.9 mg g^?1 for 0.019M and 0.049M concentrations of β‐CD‐NMA in monomer solution, respectively. The PNIPAAm‐β‐CD‐NMA‐PP showed a remarkable increase in absorbance affinity of 8‐anilino‐1‐naphthalenesulfonic acid ammonium salt at 20°C from 0.93 to 3.33 µmol g^?1 compared to PNIPAAm‐PP. Furthermore, the results showed a temperature‐sensitive loading affinity for PNIPAAm‐β‐CD‐NMA‐PP in absorbance of guest molecules due to the presence of β‐CD‐NMA. The use of hydrophobic guest molecules such as fragrance oils and antibiotics in modified fabrics can provide new applications in textile and pharmaceutical industry. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40497.     

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,evaluation, and in vitro release study of O‐carboxymethyl chitosan nanoparticles loaded with gentamicin and salicylic acid

To inhibit the ototoxicity of gentamicin (GM) and overcome the drawback related to chitosan (CS) nanoparticles preparation in acid solution, O‐carboxymethyl chitosan (O‐CMC) nanoparticles loaded with GM and salicylic acid (SA) were prepared by ionic cross‐linking method using calcium chloride as crosslinking agent. The Fourier transform infrared (FTIR) spectroscopy and X‐ray diffraction (XRD) were used to analyze the reaction of O‐CMC and crosslinking agent. The parameters of preparation of the compound nanoparticles including the concentration of O‐CMC, the mass ratio of O‐CMC to calcium chloride, and the feed ratio of SA to GM were investigated. The results showed that the obtained nanoparticles had a high zeta potential and drug‐loading capacity. The nanoparticles were characterized by a spherical morphology, with average size ranging from 148 to 345 nm and a narrow particle size distribution. In vitro release studies in phosphate buffer saline (pH 7.4) evidenced a burst release in the first 1 h, followed by a sustained release in the residual time. The release amount of SA and GM were approximately equal in 24 h, which indicated that the SA‐ and GM‐loaded O‐CMC nanoparticles are a promising carrier system for inhibiting the ototoxicity of GM. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Drug‐delivery system based on core–shell‐type nanoparticles composed of poly(γ‐benzyl‐L‐glutamate) and poly(ethylene oxide)

A block copolymer based on poly(γ‐benzyl‐L ‐glutamate) (PBLG) as the hydrophobic part and poly(ethylene oxide) (PEO) as the hydrophilic part was synthesized and characterized. PBLG/PEO/PBLG (GEG) block copolymer nanoparticles were prepared using the dialysis technique. Fluorescence spectroscopy measurement suggested that GEG block copolymers were associated in water to form polymeric micelles and the critical micelle concentration (CMC) value of the GEG‐50 block copolymer was 0.0084 g/L. Particle‐size distribution of the GEG‐50 block copolymer based on the number average was 34.9 ± 17.6 nm. Also, the particle size and drug‐loading contents of GEG nanoparticles were significantly changed with the initial solvent used. From transmission electron microscope (TEM) observations, the GEG polymeric micelle was a nice spherical shape and the sizes ranged from approximately 20–60 nm in diameter. Results from assessing the drug‐loading contents against the initial solvent showed that the use of tetrahydrofuran (THF) or 1,4‐dioxane as the initial solvent resulted in higher drug‐loading contents than those of other solvents. In the drug‐release studies, the higher the molecular weight of the polymer and drug‐loading contents, the slower the drug release. Also, the initial solvent used was significantly affected not only in the drug‐loading contents but also in the drug‐release kinetics. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 75: 1115–1126, 2000     

Inclusion complex of cantharidin with β‐cyclodextrin: Preparation,characterization, in vitro and in vivo evaluation

Because of low aqueous solubility and slow dissolution rate, cantharidin has a low oral bioavailability. Our research aims to prepare the inclusion complex of cantharidin and β‐cyclodextrin (β‐CD) and accomplish characterization, in vitro and in vivo evaluation. CA‐β‐CD inclusion complex was prepared by saturated solution method. The CA was demonstrated by HPLC in vitro experiment and by GC‐MS in vivo experiment. CA‐β‐CD inclusion complex was characterized by differential scanning calorimetry (DSC), X‐ray diffractometry (XRD), and nuclear magnetic resonance (NMR). Through complexation with β‐CD, the solubility of CA in neutral aqueous solution was improved significantly. CA‐β‐CD inclusion complex also shows a significantly improved dissolution rate in comparison with free CA. Comparison of the pharmacokinetics between CA‐β‐CD inclusion complex and free CA was performed in rats. The in vivo results show that CA‐β‐CD inclusion complex has earlier t_max, higher C_max, and higher bioavailability than free CA after oral dosing. By comparing the AUC_0–t of CA and CA‐β‐CD inclusion complex, the relative bioavailability of CA‐β‐CD inclusion complex to free CA was 506.3%, which highlighted the evidence of significantly improved bioavailability of formulation of CA with β‐CD. Thus, this β‐CD‐based drug delivery system should be an effective oral dosage form to improve oral bioavailability of CA. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Surfactant‐free nanoparticles of poly(DL‐lactide‐co‐glycolide) prepared with poly(L‐lactide)/ poly(ethylene glycol)

Surfactant‐free nanoparticles of poly(DL ‐lactide‐co‐glycolide) (PLGA) nanoparticles were prepared with or without poly(L ‐lactide)‐poly(ethylene oxide) (LE) diblock copolymer (abbreviated as PLGA/LE and PLGA nanoparticles) by dialysis method. LE diblock copolymer was used to make PLGA nanoparticles to alternate conventional surfactant. The size of PLGA and PLGA/LE nanoparticles was 295.3 ± 171.3 and 307.6 ± 27.2 nm, respectively, suggesting LE diblock copolymer might be coated onto the surface of nanoparticles. Observation of scanning electron microscope (SEM) showed that PLGA/LE nanoparticles have spherical shapes ranging ～ 200–500 nm. In ¹H‐NMR study, characteristic peaks of the methyl protons of PLGA disappeared in D₂O, whereas characteristic peaks of the methyl proton of both PEG and PLGA were shown in both CDCl₃ and D₂O, indicating that LE diblock copolymer coated on the surface of the PLGA nanoparticles. The higher the initial content of drug, the higher the drug contents and the lower the loading efficiency. PLGA/LE nanoparticles at higher drug contents resulted in slower adriamycin·HCl (ADR) release rate than that of lower drug contents. Also, slower release rate of ADR was achieved by entrapped into the PLGA/LE nanoparticles, whereas LE polymeric micelles showed rapid ADR release. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 1116–1123, 2003     

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     

Preparation and characterization of β‐cyclodextrin‐linked chitosan microparticles

Hydrophobically modified chitosan containing β‐cyclodextrin (CD) units was synthesized by using tosylated β‐CD. The final product was characterized by Fourier transform infrared (FTIR) spectroscopy, elemental analysis and TGA, and rheometry. The polymer bearing β‐CD moieties was used to obtain crosslinked microparticles by spray‐drying which could then be used in a controlled release system for drugs. FTIR confirmed the formation of an amide linkage between cyclodextrin and chitosan. As fluorescence spectroscopy demonstrated, hydrophobic microenvironments were formed by chitosan bearing cyclodextrin in solution at lower concentrations than for chitosan. Rheometry and FTIR showed the crosslinking of the new polymer using genipin, a molecule of natural origin. Microspheres (MS) obtained by spray‐drying showed narrow size distribution when β‐CD was grafted onto chitosan and ξ‐potential of MS was slightly lower although it remained positive. In conclusion, β‐CD linked chitosan polymer can be considered as a very promising controlled drug delivery system for drugs. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Development of ultrasmall chitosan/succinyl β‐cyclodextrin nanoparticles as a sustained protein‐delivery system

In this article, we introduce a new method for preparing ultrasmall chitosan (CS)/succinyl β‐cyclodextrin (SCD) nanoparticles (NPs) intended for loading bovine serum albumin (BSA) as a model protein. The proposed method is based on the complex coacervation technique followed by ionotropic gelation with tripolyphosphate. SCD, an anionic derivative of cyclodextrin, was synthesized and used in CS‐based NPs to enhance the entrapment efficiency of BSA. The results show that with this approach, ultrasmall, compact, and neutralized NPs with a mean particle size near 30 nm were obtained. A high degree of protein entrapment in the NPs led to a significant improvement in the BSA release profile with a low initial burst release (ca. 3% w/v of the initially loaded BSA) and a sustained release over time. This enabled a suitable nanocarrier for long‐term protein delivery (30% release over 120 h). © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39648.     

Adsorption of guanosine,cytidine, and uridine on a β‐cyclodextrin derivative grafted chitosan

A β‐cyclodextrin derivative grafted chitosan (CDD‐C) was synthesized with chitosan and carboxymethyl‐β‐cyclodextrin (β‐CD). Its structure was characterized by elemental, infrared spectra, and X‐ray diffraction analyses. The degree of substitution by the carboxymethyl‐β‐CD moiety achieved 0.27 with the addition of DMF to the reaction solution. The results are in agreement with the expectations. The static adsorption properties for guanosine, cytidine, and uridine were studied. Experimental results demonstrated that CDD‐C had higher adsorption capability for guanosine than cytidine and uridine, and the adsorption capacity for guanosine was 74.20 mg/g. The adsorption capacity was greatly influenced by pH, time, and temperature. The introduction of chitosan enhanced the adsorption ability and adsorption selectivity of β‐CD for guanosine. This novel derivative of chitosan is expected to have wide applications in separation, concentration, and analysis of guanosine, cytidine, and uridine in biological sample. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 3050–3055, 2007     

Adsorption and drug release based on β‐cyclodextrin‐grafted hydroxyapatite composite

In this study, β‐cyclodextrin (β‐CD) was covalently grafted on hydroxyapatite (HA) using a coupling agent to improve the drug loading capacity and prolong the drug release. The binding of β‐CD on the HA surface was confirmed by Fourier transformation infrared spectroscopy, thermal gravimetric analysis, and X‐ray powder diffraction. The adsorption capacity of ofloxacin on β‐CD‐grafted hydroxyapatite (β‐CD‐g‐HA) composite was found to be 30 mg g^?1 at 37°C and 24 h. The adsorption process is spontaneous, given the negative values of free energy change. Compared with the release of ofloxacin loaded on HA, the release of ofloxacin loaded on β‐CD‐g‐HA was slowed down 28% and 21% in pH 2.0 and pH 7.4 buffer media at 2 h, respectively. Biocompatibility of β‐CD‐g‐HA was assessed by MTT assay, and the result showed that it had no cytotoxicity. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

β‐cyclodextrin‐conjugated hyaluronan hydrogel as a potential drug sustained delivery carrier for wound healing

In order to develop a potential drug sustained delivery carrier suitable for wound healing, a series of β‐cyclodextrin conjugated hyaluronan hydrogels (β‐CD‐HA) with adjustable crosslink densities were synthesized and characterized, meanwhile the delivery kinetics and mechanism of diclofenac as a model anti‐inflammatory drug from these hydrogels were investigated. By controlling the feeding molar ratio of β‐CD/HA, a β‐CD substitution degree of 4.65% was obtained by ¹H‐NMR analysis. The incorporation of β‐CD modification had little effect on the internal porous structure, water swelling ratio, and rheological property of HA hydrogel, which however were influenced by the crosslink density. Although the crosslink density had an influence on the drug loading and release profile by altering the water swelling property, the interaction between β‐CD and drug was the primary factor for the high loading capacity and long‐term sustained delivery of diclofenac. The semiempirical equation fit showed that the release of diclofenac from HA‐based hydrogels followed a pseudo‐Fickian diffusion mechanism. By the aid of β‐CD and controlled crosslink density, a β‐CD‐HA hydrogel with a diclofenac sustained delivery period of over 28 days and desirable physicochemical properties was achieved, which will be a promising drug sustained delivery carrier for wound healing. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43072.     

Influence of polymer morphology on the adsorption behaviors of molecularly imprinted polymer‐methacrylic acid functionalized β‐cyclodextrin

The influence of molecularly imprinted polymer‐methacrylic acid functionalized β‐cyclodextrin (MIP(MAA‐β‐CD)) morphology on the adsorption behavior studies towards benzylparaben (BzP) was explored. The effects of time, concentration, and temperature towards BzP uptake were extensively evaluated. The adsorption performance of MIP(MAA‐β‐CD) was compared with that on the molecularly imprinted polymer‐methacrylic acid (MIP(MAA)) synthesized without β‐CD. The MIP(MAA‐β‐CD) was synthesized to obtain a spherical and spongy‐porous texture with a broad pore size distribution. The MIP(MAA‐β‐CD) showed fast kinetic and the intra‐particle diffusion model demonstrated a three step (surface and pore) adsorption process. The Koble‐Corrigan isotherm was the most suitable model for data fitting, which indicated that MIP(MAA‐β‐CD) had homogeneous and heterogeneous surfaces. This finding clearly demonstrated that the large uptake and strong affinity of MIP(MAA‐β‐CD) did not only probably result from the monomer‐template interactions, but also due to the morphological MIP(MAA‐β‐CD) structure. In contrary to MIP(MAA‐β‐CD), MIP(MAA) synthesized with uniform morphology and narrow pore size distribution had lower adsorption capacities and its kinetic data fitted the pseudo‐second order diffusion model, indicating a two‐step (surface only) adsorption process. The MIP(MAA) adsorption process followed the Langmuir isotherm model referred to solely homogeneous uptake. The calculated thermodynamic parameters showed that the BzP uptake was exothermic, spontaneous, and physisorption process onto MIPs, which supported the results of kinetics and isotherm adsorption data. This study clearly revealed that the presence of β‐CD improved the morphology of synthesized MIP, and automatically enhanced the adsorption behavior of MIP. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42720.     

pH‐sensitive Podophyllotoxin carrier for cancer cells specific delivery

A pH‐sensitive drug targeting system for solid tumors was established based on N‐isopropylacrylamide (NIPAAm) and chitosan conjugates. The mass ratio of NIPAAm and chitosan was adjusted to obtain super pH‐sensitive characteristic and the structure was studied by using Fourier transform infrared spectroscope to confirm the successful synthesis of the nanoparticles. The pH‐sensitive and drug release characteristics in vitro were studied as well. Human lung cancer cells A‐549 and human fibroblast were used to test the biocompatibility of blank and Podophyllotoxin (POD) loaded nanoparticles further to certificate the reliability of targeting acidic tumor extracellular pH. Results revealed that when charge ratio between NIPAAm and CS achieve 4:1(w/w), the drug‐loaded nanoparticles, which diameters ranged from 50 to 150 nm, exhibited super pH‐sensitive responses to tumor pH. Encapsulation and loading efficiencies were 63.7% and 2.4%, respectively. The cumulative release rate of POD, which significantly enhanced at pH 6.8 while decreased rapidly either below pH 6.5 or above pH 6.9 at 37°C. At pH 6.8, POD‐loaded nanoparticles showed cytotoxicity in MTT test and fluorescence microscopic study, comparable to that of free POD at the same POD concentrations, whereas at pH 7.4 there was little cytotoxicity at the tested concentration range. Thereby, the atoxic PNIPAAm‐g‐chitosan nanoparticle has the potentiality as a novel anticancer drugs carrier. POLYM. COMPOS., 2010. © 2009 Society of Plastics Engineers     

Controlled co‐delivery of hydrophilic and hydrophobic drugs from thermosensitive and crystallizable copolymer nanoparticles

Functionalized amphiphilic block copolymers poly(N‐isopropyl acrylamide)‐b‐poly(stearyl methacrylate) (PNIPAM‐PSMA) are synthesized. Their self‐assembled core‐shell nanoparticles have the hydrophilic thermosensitive shell and hydrophobic crystallizable core. Nanoparticles exhibit volume phase transition at temperature of 38 °C and its poly(stearyl methacrylate) (PSMA) moiety could form nano size crystals to retain drugs, making them good carriers for drug co‐delivery system. Thermosensitivity and crystallinity of nanoparticles are characterized with dynamic light scattering (DLS), differential scanning calorimetry (DSC), small‐angle X‐ray scattering (SAXS), and atomic force microscopy (AFM). The interactions and relationship between chemical structures of copolymer nanoparticles and loading drugs are discussed. Different loading techniques and combined loading of hydrophobic/hydrophilic drugs are studied. Nanoparticles show a good and controllable drug loading capacity (DL) of hydrophilic/hydrophobic drugs. The drugs release kinetics is analyzed with Fick's law and Weibull model. A general method for analyzing drug release kinetics from nanoparticles is proposed. Weibull model is well fitted and the parameters with definite physical meaning are analyzed. PNIPAM‐PSMA nanoparticles show a quite different thermal response, temporal regulation, and sustained release effect of hydrophilic and hydrophobic drugs, suggesting a promising application in extended and controlled co‐delivery system of multi‐drug. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 44132.     

Chitosan‐modified d‐α‐tocopheryl poly(ethylene glycol) 1000 succinate‐b‐poly(ε‐caprolactone‐ran‐glycolide) nanoparticles for the oral chemotherapy of bladder cancer

Oral chemotherapy is quickly emerging as an appealing option for cancer patients. It is less stressful because the patient has fewer hospital visits and can still maintain a close relationship with health care professionals. Three kinds of nanoparticles made from commercial poly(ε‐caprolactone) (PCL) and self‐synthesized d‐α‐tocopheryl poly(ethylene glycol) 1000 succinate ‐b‐poly(ε‐caprolactone‐ran‐glycolide) [TPGS‐b‐(PCL‐ran‐PGA)] diblock copolymer were prepared in this study for the oral delivery of antitumor agents, including chitosan‐modified PCL nanoparticles, nonmodified TPGS‐b‐(PCL‐ran‐PGA) nanoparticles, and chitosan‐modified TPGS‐b‐(PCL‐ran‐PGA) nanoparticles. First, the TPGS‐b‐(PCL‐ran‐PGA) diblock copolymer was synthesized and structurally characterized. Chitosan was adopted to extend the retention time at the cell surface and thus increase the chance of nanoparticle uptake by the gastrointestinal mucosa and improve the absorption of drugs after oral administration. The resulting TPGS‐b‐(PCL‐ran‐PGA) nanoparticles were found to be of spherical shape and around 200 nm in diameter with a narrow size distribution. The surface charge of the TPGS‐b‐(PCL‐ran‐PGA) nanoparticles could be reversed from anionic to cationic after surface modification. The chitosan‐modified TPGS‐b‐(PCL‐ran‐PGA) nanoparticles displayed a significantly higher level of cellular uptake compared with the chitosan‐modified PCL nanoparticles and nonmodified TPGS‐b‐(PCL‐ran‐PGA) nanoparticles. In vitro cell viability studies showed the advantages of the chitosan‐modified TPGS‐b‐(PCL‐ran‐PGA) nanoparticles over Taxol in terms of their cytotoxicity against human RT112 cells. In summary, the oral delivery of antitumor agents by chitosan‐modified TPGS‐b‐(PCL‐ran‐PGA) nanoparticles produced results that were promising for the treatment of patients with bladder cancer. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 2118–2126, 2013     

Preparation and characterization of poly{[α‐maleic anhydride‐ω‐methoxy‐poly(ethylene glycol)]‐co‐(ethyl cyanoacrylate)} copolymer nanoparticles

Poly{[α‐maleic anhydride‐ω‐methoxy‐poly(ethylene glycol)]‐co‐(ethyl cyanoacrylate)} (PEGECA) copolymers were prepared by radical polymerization of macromolecular poly(ethylene glycol) monomers (PEGylated) and ethyl 2‐cyanoacrylate in solvent. The structures of the copolymer were characterized by Fourier‐transform infrared (FTIR) and proton nuclear magnetic resonance (¹H‐NMR). The morphology and size of the PEGECA nanoparticles prepared by nanoprecipitation techniques were investigated by transmission electron microscopy (TEM) and photon correlation spectroscopy (PCS) methods. The results show that the PEGECA can self‐assemble into highly stable nanoparticles in aqueous media, and inner core and outer shell morphology. The size of the nanoparticles was strongly influenced by the solvent character and the copolymer concentration in the organic solvents. A hydrophobic drug, ibuprofen, was effectively incorporated into the nanoparticles, which provides a delivery system for ibuprofen and other hydrophobic compounds. Copyright © 2005 Society of Chemical Industry