Development of fibrin conjugated chitosan/nano β‐TCP composite scaffolds with improved cell supportive property for bone tissue regeneration

In the present study, an attempt has been made to improve cell supportive property of chitosan/nano beta tri‐calcium phosphate (β‐TCP) composite scaffolds by modification of scaffold surface with fibrin using ethyl‐3‐(3‐dimethylaminopropyl) carbodimide (EDC) as crosslinking agent. The developed fibrin conjugated chitosan/nano β‐TCP composite scaffolds possess desired pore size and porosity in the range of 45–151 µm and 81.4 ± 4.1%, respectively. No significant change in compressive strength of scaffolds was observed before and after fibrin conjugation. The calculated compressive strength of fibrin conjugated and non‐conjugated chitosan/nano β‐TCP scaffolds are 2.71 ± 0.14 MPa and 2.67 ± 0.11 MPa, respectively. Results of cell culture study have further shown an enhanced cell attachment, cell number, proliferation, differentiation, and mineralization on fibrin conjugated chitosan/nano β‐TCP scaffold. The uniform cell distribution over the scaffold surface and cell infiltration into the scaffold pores were assessed by confocal laser scanning microscopy. Furthermore, higher expression of osteogenic specific genes such as bone sialo protein, osteonectin, alkaline phosphatase, and osteocalcin (OC) on fibrin conjugated scaffolds was observed when compared to scaffolds without fibrin. Altogether, results indicate the potentiality of developed fibrin conjugated composite scaffolds for bone tissue engineering applications. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41534.     

Fabrication of PCL/β‐TCP scaffolds by 3D mini‐screw extrusion printing

Scaffolds of polycaprolactone (PCL) and PCL composites reinforced with β‐tricalcium phosphate (β‐TCP) were manufactured aiming potential tissue engineering applications. They were fabricated using a three‐dimensional (3D) mini‐screw extrusion printing, a novel additive manufacturing process, which consists in an extrusion head coupled to a 3D printer based on the Fab@Home equipment. Thermal properties were obtained by differential scanning calorimetry and thermogravimetric analyses. Scaffolds morphology were observed using scanning electron microscopy and computed microtomography; also, reinforcement presence was observed by X‐ray diffraction and the polymer chemical structure by Fourier transform infrared spectroscopy. Mechanical properties under compression were obtained by using a universal testing machine and hydrophilic properties were studied by measuring the contact angle of water drops. Finally, scaffolds with 55% of porosity and a pore size of 450 μm have shown promising mechanical properties; the β‐TCP reinforcement improved mechanical and hydrophilic behavior in comparison with PCL scaffolds. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43031.     

Surface‐engineered hydroxyapatite nanocrystal/ poly(ε‐caprolactone) hybrid scaffolds for bone tissue engineering

To achieve novel polymer/bioceramic composite scaffolds for use in materials for bone tissue engineering, we prepared organic/inorganic hybrid scaffolds composed of biodegradable poly(ε‐caprolactone) (PCL) and hydroxyapatite (HA), which has excellent biocompatibility with hard tissues and high osteoconductivity and bioactivity. To improve the interactions between the scaffolds and osteoblasts, we focused on surface‐engineered, porous HA/PCL scaffolds that had HA molecules on their surfaces and within them because of the biochemical affinity between the biotin and avidin molecules. The surface modification of HA nanocrystals was performed with two different methods. Using Fourier transform infrared, X‐ray diffraction, and thermogravimetric analysis measurements, we found that surface‐modified HA nanocrystals prepared with an ethylene glycol mediated coupling method showed a higher degree of coupling (%) than those prepared via a direct coupling method. HA/PCL hybrid scaffolds with a well‐controlled porous architecture were fabricated with a gas‐blowing/particle‐leaching process. All HA/PCL scaffold samples exhibited approximately 80–85% porosity. As the HA concentration within the HA/PCL scaffolds increased, the porosity of the HA/PCL scaffolds gradually decreased. The homogeneous immobilization of biotin‐conjugated HA nanocrystals on a three‐dimensional, porous scaffold was observed with confocal microscopy. According to an in vitro cytotoxicity study, all scaffold samples exhibited greater than 80% cell viability, regardless of the HA/PCL composition or preparation method. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Formulation of silver chloride/poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) (AgCl/PHBV) films for potential use in bone tissue engineering

Orthopedic implant failure due to bacterial infection has been a concern in bone tissue engineering. Here, we have formulated a composite made of biodegradable polymer, i.e., poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) (PHBV), and silver chloride. Ag⁺ ions released from the AgCl/PHBV film can promote an aseptic environment by promoting inhibition of bacterial growth while maintaining bone cell growth, depending on AgCl loading. The objective of this study is to formulate AgCl/PHBV film(s) of varying composition so as to evaluate the dependence of AgCl loading in the film on antimicrobial activity and cytotoxicity. The release kinetics of silver ions from AgCl/PHBV film in aqueous and Dulbecco's Modified Eagle Medium showed similarity in the initial burst of ions during the first day of desorption followed by a gradual release of ions over extended time period. The antibacterial efficacy of AgCl/PHBV film against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa was evaluated by microbiological assay, while cytotoxicity of the film toward MC3T3‐E1 cells was determined by MTT assay. For all compositions studied, a clear zone of inhibition around AgCl/PHBV film was noticed on a modified Kirby‐Bauer disk diffusion assay. We established that MC3T3‐E1 cell attachment on AgCl/PHBV film is strongly related to loading of AgCl in the film. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45162.     

Characterization of ketoprofen‐loaded PEG‐CH semi‐IPN system for wound dressing application

Polymer systems, in the form of crosslinking networks, have been widely used in biomedicine. However, they are a challenge mainly due to the impact of their physicochemical properties on release kinetics of drugs. Ketoprofen is an analgesic anti‐inflammatory drug with short half‐life (<2 h) and quickly eliminated by the body. Topical administration of ketoprofen can reduce pain, accelerate the wound healing process, and minimize the risk of systemic side effects. Therefore, the aim was to synthesize, characterize, and evaluate a novel ketoprofen polymer system in the form of a semi‐interpenetrated network of poly(ethylene glycol)‐chitosan. The pore size studied by small‐angle X‐ray scattering showed the presence of nanoscale pores, 13.7 nm (dry state) and 26.18 nm (swollen form). The maximum swelling was 420 ± 45% at 24 h. Finally, the encapsulated ketoprofen (6.5%) was released at a constant concentration (0.12 ± 0.03 mg/mL, 8 h) and half of the doses up to 24 h. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46644.     

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.     

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     

Incorporation of chloramphenicol and captopril into poly(GL)‐b‐poly(GL‐co‐TMC‐co‐CL)‐b‐poly(GL) monofilar surgical sutures

Incorporation of chloramphenicol and captopril into coated and uncoated monofilament sutures was evaluated, as well as the derived bactericide and wound healing effects. To this end, a commercially available suture and an amorphous random copolymer constituted by trimethylene carbonate and lactide units were considered. The suture had a segmented architecture based on polyglycolide hard blocks and a soft block constituted by glycolide, trimethylene carbonate and ε‐caprolactone units. Chloramphenicol was better loaded when the coating copolymer was employed due to its protective effect whereas captopril showed an opposite behavior due to partial solubilization during immersion in the coating bath. Interestingly, the release behavior was very different for the two studied drugs since a significant retention of chloramphenicol was always detected, suggesting the establishment of interactions between drug and copolymers. On the other hand, delivery of captopril showed a typical dose dependent behavior. A low in vitro toxicity of the two drugs was determined considering both epithelial‐like and fibroblast‐like cells. Bactericide effect of chloramphenicol against Gram‐negative and Gram‐positive bacteria was demonstrated at a dose that was non‐toxic for all assayed cells. An accelerating wound healing effect of captopril was also demonstrated for early events. In this case, the use of a coating copolymer was fundamental to avoid cytotoxic effects on highly loaded sutures. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44762.     

5‐Fluorouracil encapsulated magnetic nanohydrogels for drug‐delivery applications

For the first time, green‐tea (GT)‐based magnetic nanohydrogels were developed for drug‐delivery purposes. The hydrogel matrices were fabricated via the in situ polymerization of acrylamide with GT molecules. Magnetic nanoparticles were synthesized by the reduction of the 1:2 molar ratio mixture of ferrous sulfate heptahydrate and ferric chloride hexahydrate with an ammonia solution. A chemotherapeutic drug, 5‐fluorouracil, was chosen as a model drug, and its releasing profiles in the presence and absence of the external magnetic field were evaluated at a pH of 7.4. We observed that in the presence of the applied magnetic field, these magnetic nanohydrogels released 2.86% more drug than in the absence of a magnetic field. The magnetic nanohydrogels were characterized by X‐ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, vibrating sample magnetometry, and transmission electron microscopy. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43921.     

Herbally derived polymeric nanofibrous scaffolds for bone tissue regeneration

Hydroxyapatite (HA), the bone mineral and Cissus quadrangularis (CQ), a medicinal plant with osteogenic activity, are attaining increasing interest as a potential therapeutic agent for enhanced bone tissue regeneration. In the present study a synergistic effect of these two agents were analyzed by fabricating PCL‐CQ‐HA nanofibrous scaffolds by electrospinning and compared with PCL‐CQ and PCL (control) nanofibrous scaffolds. Morphology, composition, hydrophilicity, and mechanical properties of the electrospun PCL, PCL‐CQ, PCL‐CQ‐HA nanofibrous scaffolds were examined by Field emission scanning electron microscopy (FESEM), Fourier transform infrared spectroscopy (FTIR), Contact angle and Tensile tests, respectively. The response of human foetal osteoblast cells on these scaffolds were evaluated using MTS assay, alkaline phosphatase activity, alizarin red staining, and osteocalcin expression for bone tissue regeneration. While the observed cellular response to both groups of scaffolds was better than for the control PCL scaffold, the PCL‐CQ‐HA nanofibrous scaffolds provided the most favorable substrate for cell proliferation and mineralization. The results showed that PCL‐CQ‐HA nanofibrous scaffolds had appropriate surface roughness for the osteoblast adhesion, proliferation, and mineralization comparing with other scaffolds. The observed investigation of physicochemical and biological properties suggests that the CQ‐HA loaded PCL nanofibrous scaffolds serve as a potential biocomposite material for bone tissue engineering. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39835.     

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.     

Multifunctional ternary drug‐loaded electrospun scaffolds

Multifunctional electrospun scaffolds were prepared from two polylactide (PLA) grades having slightly different d ‐lactide content (4.2 wt % and 2.0 wt %). Triclosan (TCS), ketoprofen (KTP), and p‐coumaric acid (CUM) were selected as bactericide, anti‐inflammatory, and antioxidant agents, respectively. Single, binary, and ternary drug‐loaded microfibers having a unimodal diameter distribution could be prepared using a common chloroform:acetone:dimethylsulfoxide mixture and similar operational parameters (i.e., voltage, flow rate, and tip–collector distance). FTIR spectra were sensitive to the low amount of drugs loaded and even showed slight differences in PLA conformation. DSC heating scans clearly demonstrated the ability of electrospinning to induce molecular orientation of PLA and also the nucleation effect of incorporated drugs to induce crystallization. Thus, crystallinity of binary drug‐loaded scaffolds was significantly higher than observed for unloaded samples. Release behavior of the three drugs from loaded scaffolds and PLA matrices in PBS:ethanol medium was evaluated. A rapid release was always detected, together with partial drug retention which was higher when the more stereoregular PLA matrix was employed. A strong bactericidal effect was found when scaffolds were loaded with 3 wt/vol % of TCS, but incorporation of a small percentage of KTP (i.e., 1 wt/vol %) had a bacteriostatic effect even in the absence of TCS. The inherent cytotoxicity of TCS could be well neutralized by enhancing cell viability by incorporation of CUM and/or KTP. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 42751.     

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.     

Effects of micro and nano β‐TCP fillers in freeze‐gelled chitosan scaffolds for bone tissue engineering

Tissue engineering holds an exciting promise in providing a long‐term cure to bone‐related defects and diseases. However, one of the most important prerequisites for bone tissue engineering is an ideal platform that can aid tissue genesis by having biomimetic, mechanostable, and cytocompatible characteristics. Chitosan (CS) was chosen as the base polymer to incorporate filler, namely beta‐tri calcium phosphate (β‐TCP). This research deals with a comparative study on the properties of CS scaffolds prepared using micro‐ and nano‐sized β‐TCP as filler by freeze gelation method. The scaffolds were characterized for their morphology, porosity, swelling, structural, chemical, biodegradation, and bioresorption properties. Rheological behavior of polymer and polymer‐ceramic composite suspensions were analyzed and all the suspensions with varying ratios of β‐TCP showed non‐Newtonian behavior with shear thinning property. Pore size, porosity of micro‐ and nano‐sized composite scaffolds are measured as 48–158 μm and 77% and 43–155 μm and 81%, respectively. The scaffolds containing nano β‐TCP possess higher compressive strength (～2.67 MPa) and slower degradation rate as compared to composites prepared with micro‐sized β‐TCP (～1.52 MPa). Bioresorbability, in vitro cell viability by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay, proliferation by Alamar blue assay, cell interaction by scanning electron microscope, and florescence microscopy further validates the potentiality of freeze‐gelled CS/β‐TCP composite scaffolds for bone tissue engineering applications. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41025.     

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     

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.     

Preparation of ibuprofen‐loaded HDPE tubular devices for application as urinary catheters

In this study, high‐density polyethylene tubes with the incorporation of ibuprofen (IBP) were investigated with a view to their application as urinary catheters. The melt extrusion process was used to prepare the urinary catheters, and the influence of the manufacturing parameters on the material properties was evaluated. Samples prepared at lower temperature resulted in a more homogeneous material with a smoother surface, lower crystallinity, and better mechanical properties. The drug release was faster in the first 4 days, due to the accumulation of the drug on the outer surface of tubes. The concentration of IBP released was similar to the drug content in commercially available topic formulations (5%). Furthermore, after 2 days of immersion, the release achieved the concentration known to inhibit bacterial growth (6 mg/mL). These characteristics indicate that this material has good potential for application in urinary catheters. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45661.     

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.     

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.     

Temperature stimuli-responsive nanoparticles from chitosan-graft-poly(N-vinylcaprolactam) as a drug delivery system

This work describes the preparation of thermosensitive chitosan-graft-poly(N-vinylcaprolactam) nanoparticles by ionic gelation and their potential use as a controlled drug delivery system, using doxorubicin as a model drug. A systematic study of the effect of the main processing parameters on both the size and thermoresponsive behavior of nanoparticles was investigated. The size of the particles is strongly dependent on the length of the poly(N-vinylcaprolactam) grafted chains and the concentration of the copolymer and crosslinking agent solutions. The molecular structure of the copolymer plays an essential role in the phase transition temperature of the particles, which decreases with the length of PVCL grafted chain. The system displayed proper drug-association parameters, and the drug-loaded nanoparticles exhibited dose-dependent cytotoxicity. A significant increase in the doxorubicin delivery rate was observed above the phase transition temperature (40 °C). These features indicate that these nanoparticles are suitable for the development of a new thermally controlled anti-cancer drug delivery system. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47831.