Polydopamine-mediated polypyrrole/doxorubicin nanocomplex for chemotherapy-enhanced photothermal therapy in both NIR-I and NIR-II biowindows against tumor cells

Photothermal therapy (PTT) is featured by the desirable spatiotemporal controllability and excellent specificity, which has been identified as one of the important tumor treatment methods. Although promising, the efficacy of PTT is still limited and needs further improvement. In this work, a kind of PPy-PDA-PEG@DOX nanocomplex was designed and constructed for chemotherapy-enhanced PTT in both near-infrared (NIR)-I and NIR-II biowindows against tumor cells, which was integrated by the polypyrrole (PPy) core, polydopamine (PDA) shell, polyethylene glycol (PEG) linkage, and doxorubicin (DOX) payload. This constructed PPy-PDA-PEG@DOX nanocomplex was uniform in size around 56.3 nm, and with the optimized DOX loading content at 37.4%. The photothermal conversion efficiencies of this nanocomplex were calculated to be around 23.1 and 30.8% in NIR-I and NIR-II biowindows, respectively, showing good photothermal capacity and stability. The loaded DOX could be released in stimuli-responsive manners. The therapeutic efficacy was enhanced by PPy-PDA-PEG@DOX nanocomplex, indicating the high effectiveness of chemotherapy-enhanced phototherapy. This developed PPy-PDA-PEG@DOX nanocomplex shows promising applications in tumor treatment applications.     

Thermosensitive PMMA core/oligo(ethylene glycol)-based shell microgels as drug carriers in detoxification treatment

The core-shell structured polymer microgels were synthesized by coating the hydrophobic poly(methyl methacrylate) (PMMA) sphere cores with hydrophilic nonlinear poly(ethylene glycol)-based gel shell layer. The uniqueness of these core-shell microgels lies in the integration of the PMMA core microsphere with strong hydrophobicity and the novel oligo(ethylene glycol)-based gel layer with well-defined thermosensitivity for improving loading/release efficacy of two detoxification drugs (chlorpromazine and diltiazem). The hydrophilic shell is composed of hydrophilic copolymer of 2-(2-methoxyethoxy)ethyl methacrylate (MEO₂MA) with oligo(ethylene glycol) methyl ether methacrylates (MEO₅MA). It was found that the molar ratio of two shell monomers n(MEO₂MA)/n(MEO₅MA) of 1:6 was an ideal matching value for production of the P(MEO₂MA)/P(MEO₂MA-co-MEO₅MA) core-shell microgels with tunable volume phase transition temperature and excellent colloidal stability across the physiologically important temperature range. Moreover, chlorpromazine- and diltiazem-loaded microgels can show an obvious thermosensitive release and in vitro sustained-release characteristic up to 80 h.     

Enhancement of fibroblastic proliferation from photoreactive starch with immobilized epidermal growth factor

Carboxymethyl starch was modified by the incorporation of an azidophenyl group to prepare photoreactive starch, and characterized by Fourier transform infrared reflectance (FT‐IR), proton nuclear magnetic resonance (¹H‐NMR), and ultraviolet (UV) spectroscopy. Photo‐irradiation immobilized the Az‐starch on a polystyrene plate and it was stably retained on the surface. The protein containing immobilized Az‐starch was also immobilized on a stripe micropatterned plate. UV irradiation time and Az‐starch concentration were used to alter the physical properties of Az‐starch and consequently control the rate of epidermal growth factor (EGF) release. The Az‐starch that released growth factor was not cytotoxic to 3T3‐L1 fibroblast cells, and the immobilized EGF maintained its activity and induced cellular proliferation in vitro. These results suggest that Az‐starch could be useful as a clinical synthetic material for medical applications. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

p(AAm/TA)‐based IPN hydrogel films with antimicrobial and antioxidant properties for biomedical applications

Interpenetrating polymer networks (IPN), either semi‐IPN (s‐IPN) or full IPN, based on a natural polymer tannic acid (TA) and synthetic poly(acrylamide) (p(AAm)) were prepared by incorporation of TA during p(AAm) hydrogel film preparation with and without crosslinking of TA simultaneously. The synthesis of p(AAm/TA) s‐IPN and IPN hydrogels with different amounts of TA were prepared by concurrent use of redox polymerization and epoxy crosslinking. The p(AAm)‐based hydrogels were completely degraded at 37.5°C within 9 and 2 days at pHs 7.4 and 9, respectively. Biocompatibility of p(AAm), s‐IPN, and IPN were tested with WST assay and double staining, they had 75% cell viability up to almost 20 μg mL^?1 concentration against L929 fibroblast cell. Antioxidant properties of IPN and s‐IPN hydrogels were investigated with FC and ABTS^? methods. Antimicrobial properties of TA‐containing s‐IPN, and IPN hydrogels were determined against three common bacterial strains, Escherichia coli ATCC 8739, Staphylococcus aureus ATCC 6538, and Bacillus subtilis ATCC 6633, and it was found that p(AAm/TA)‐based s‐IPN and IPN hydrogels are effective antimicrobial and antioxidant materials. Moreover, almost up to day‐long linear TA release profiles were obtained from IPN and s‐IPN hydrogels in phosphate buffer solution at pH 7.4 at 37.5°C. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41876.     

Electrospun scaffolds for wound healing applications from poly(4-hydroxybutyrate): A biobased and biodegradable linear polymer with high elastomeric properties

Electrospun scaffolds of the biodegradable and biocompatible poly-4-hydroxybutyrate (P4HB) polyester have been prepared using horizontal and vertical set-up configurations of electrospinning. Specifically, it has been evaluated the influence of solvent, polymer concentration, and processing parameters, such as applied voltage, flow rate, and needle tip-collector distance. Scaffolds obtained under the most favorable conditions were characterized in terms of crystallinity, lamellar supramolecular order, thermal (including calorimetric and thermogravimetric data), mechanical, and surface properties. Results pointed out significant differences with respect to commercial sutures (based in P4HB, e.g., MonoMax®) and demonstrated that electrospun scaffolds were constituted by crystalline microfibers with a tangled distribution that leads to high modulus Young modulus (4 MPa), maximum strength (28 MPa), and elongation (360%). Furthermore, new scaffolds had thermal stability and a rough surface that led to a hydrophobic character (105°). Scaffolds could also be successfully loaded during the electrospinning process with a peptide analog to the fibroblast growth factor (e.g., CYRSRKYSSWYVALKRC), giving rise to fully biocompatible samples with a clear acceleration in wound healing.     

Aloe vera gel influence on the micellization behavior of copolymer Pluronic F127: A potential photosensitizer carrier for topical application

This work describes the influence of aloe vera gel on Pluronic F127 triblock copolymer (F127) micellization behavior. Aloe vera gel was obtained from aloe vera mucilage found in leaf pulp. F127 (20% w/w) gel and the aloe vera/F127 blend gel were obtained by using the cold method. Fourier transform infrared spectroscopy and X‐ray diffraction analyses of lyophilized samples did not show any important copolymer interaction between aloe vera gel and F127. However, in aqueous medium, the dynamic light scattering data showed that there was an important reduction in micelle size with increasing temperature of the aloe vera/F127 blend hydrogel. The differential scanning calorimetry results indicate that the aloe vera/F127 blend has a higher micellization temperature, affected by the lower dehydrating effect of the poly(propylene oxide) blocks during the micelle formation in comparison to F127 gel. The texture analyses (hardness and adhesiveness) showed that the addition of aloe vera gel did not change the Pluronic F127 gel texture properties. The photosensitizer zinc phthalocyanine (ZnPC) was incorporated into the aloe vera/F127 blend, and the results suggest that this formulation is suitable as a ZnPC delivery system for photodynamic therapy. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46191.     

A rechargeable drug delivery system based on pNIPAM hydrogel for the local release of curcumin

This study was designed to develop a drug delivery system based on poly(N-isopropylacrylamide) (pNIPAM) hydrogel and a suitable solvent to enhance solubility and local release of curcumin. pNIPAM hydrogel was synthesized by radical polymerization. The chemical, mechanical and physical properties and biocompatibility of pNIPAM hydrogel were investigated as an implantable and rechargeable drug reservoir. Curcumin was loaded within pNIPAM hydrogel during swelling by using two different solvents; methanol, an organic solvent, and low molecular weight polyethylene glycol (PEG200), a polymeric solvent. The results of drug solubility showed that using PEG200 can increase curcumin solubility more than commonly used organic solvents such as methanol. Also, the release profile of drug-loaded hydrogels demonstrated that PEG200 has a superior effect on the cumulative amount of released curcumin (33.163 ± 0.319 μg/ml) compared to methanol (8.765 ± 0.544 μg/ml) during 1 week. Based on our results, curcumin-loaded hydrogels did not show any cytotoxicity, and pNIPAM/PEG combination represented an antibacterial effect within 12 hours. Accordingly, it can be concluded that pNIPAM hydrogel in combination with low molecular weight PEG200 could be used as an efficient drug delivery system to preserve and provide sustained release of curcumin as a hydrophobic drug.     

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     

Chondrogenic stimulation in mesenchymal stem cells using scaffold-based sustained release of platelet-rich plasma

Developing minimal invasive strategies via injectable hydrogels for effective repairing of cartilage defects is highly desired. Injectable hydrogels, which can simultaneously embed cell and growth factors (GFs), serve as in situ formed scaffolds and could support an accelerated tissue regeneration process. The purpose of this study is to fabricate a composite injectable hydrogel, based on alginate (Alg)/polyvinyl alcohol (PVA) incorporating platelet rich plasma (PRP)-encapsulated Alg sulfate (AlgS) microbeads, as a localized sustained release system of GFs, for the articular cartilage regeneration. The results show that synthesized AlgS microbeads support the sustained release of PRP GFs during 14 days, where preserve the bioactivity of them more than the free PRP. Rabbit adipose-derived mesenchymal stem cells in contact with PRP-loaded AlgS beads show more proliferation (2.7 folds) and have obviously higher deposition of collagen type ΙΙ and GAGs than free PRP treated ones. In addition, cells encapsulated into the hydrogel including PRP sustained release system show upregulated expression of collagen type ΙΙ (61 folds), Aggrecan (294 folds) and SOX9 (71.5 folds), as cartilage-critical genes, compared to the direct treatment by PRP. To summarize, the developed hybrid Alg/PVA hydrogel embedding with PRP-encapsulated AlgS microbeads is suggested as a potential in situ formed scaffold for cartilage regeneration.     

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.     

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.     

Sustained release of potassium diclofenac from a pH‐responsive hydrogel based on gum arabic conjugates into simulated intestinal fluid

This work describes the preparation, the swelling properties and the potassium diclofenac (KDF) release profile of hydrogels of gum arabic (GA), N′,N′‐dimethylacrylamide, and methacrylic acid. In order to convert GA into a hydrogel, the polysaccharide was vinyl‐modified with glycidyl methacrylate. The hydrogels showed pH‐responsive swelling changes, which were more expressive in the basic environment. Release data of KDF were adjusted to a diffusion‐based kinetic model that provides an important insight on affinity of the drug for hydrogel and solvent, which may be the leading parameter for release of guest molecules from polymers. The KDF release from the hydrogels into simulated intestinal fluid decreases when the amount of modified GA increases. This was demonstrated to be due to the higher affinity of KDF for GA‐richer hydrogel, which makes the anti‐inflammatory release less favorable. The analysis of released drug half‐time (t_1/2 = 16.10 and 21.51 h) indicated sustained release characteristics. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43319.     

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.     

In vitro and in vivo evaluation of degradability and biocompatibility of poly(p-dioxanone) hemostatic clips for laparoscopic surgery

For the clinical application of biodegradable hemostatic surgical clips in laparoscopic surgery, it is necessary to determine their degradability and biocompatibility. Herein, in vitro and in vivo studies were undertaken to evaluate the degradability and biocompatibility of bioabsorbable clips made of poly(p-dioxanone). Changes in weight loss, pull-off force, differential scanning calorimetry (DSC), and scanning electron microscopy (SEM) of the poly(p-dioxanone) clips were determined after they were degraded in deionized water and phosphate buffer saline for the in vitro experiment and in laparoscopic models of bile duct ligation(BDL) and right gastroepiploic artery ligation(GEAL) using New Zealand white rabbits for the in vivo experiment. Changes in weight loss and pull-off force were greater in the in vivo experiment than the in vitro experiment. DSC showed the greatest variation in the degree of crystallinity of the clips degraded in deionized water. Stark differences in SEM were observed after 4 weeks of degradation both in vitro and in vivo. Furthermore, the cytocompatibility of the clips was considered satisfactory because the L929 cells could adhere to the clips and proliferate adequately in the presence of the clip extract. Biocompatibility was inferred based on the histological analysis of BDL and GEAL, no significant inflammatory responses were observed after 4 weeks of ligation.     

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.     

Novel electrospun nanofibers incorporating polymeric prodrugs of ketoprofen: Preparation,characterization, and in vitro sustained release

A facile and efficient protocol for the preparation of nanofibers incorporating polymeric ketoprofen prodrugs and polyvinylpyrrolidone was developed. Polymeric ketoprofen prodrugs were constructed by a two‐step chemo‐enzymatic synthetic route, and nanofibers prepared by electrospinning from dimethylformamide/ethanol (1 : 1, v/v) solutions. The morphological characteristics of the fibers were influenced by the concentration of active agent in the spinning solution; average diameters varied from 196 to 370 nm. In vitro release studies indicated that the ketoprofen release rate from the electrospun fibers was significantly higher than that from the pure polymeric prodrugs. Cumulative drug release from the electrospun fibers reached 40–70% after 3 h and 75–100% after 12 h, while the pure polymeric prodrug released only 7–9% of the active agent over 12 h. Functional nanofibers incorporating polymeric prodrugs therefore comprise potentially effective drug delivery systems for sustained release. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 1570–1577, 2013     

Electrospun curcumin/polycaprolactone/copolymer F-108 fibers as a new therapy for wound healing

The application of fibers associated with drugs is a promising alternative to meet the clinical needs of tissue repair. Curcumin exhibits great cicatricial potential because it has numerous pharmacological properties. This research aimed to produce fibers of polycaprolactone and copolymer F-108 associated with curcumin and to evaluate in vivo their action on the process of wound healing. The fibers were produced by electrospinning technique and characterized by scanning electron microscopy (SEM), X-ray diffractometry (XRD), and fluorescence microscopy. They were applied in cutaneous wounds of rats for the analysis of photoacoustic permeation and histological study. The characterization showed that the electrospinning allowed the preparation of homogeneous material with curcumin. The fibers benefited healing of the wounds and allowed the permeation of curcumin at all stages. The use of PCL/F-108 fibers allowed the elaboration of a new curcumin delivery system, improving its bioavailability and action in the healing of excisional wound. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48415.     

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.     

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.