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.     

Investigation on characterization and transfection of a novel multi‐polyplex gene delivery system

pDNA was condensed by polycationic peptide polylysine (PLL) to form a core, and then encapsulated in biodegradable monomethoxy (poly ethylene glycol)-poly(lactide-co-glycolide)-monomethoxy (poly ethylene glycol) (PELGE) to form core-shell nanoparticles (NPs) as a novel multi-polyplex gene delivery system—PPD(PELGE-PLL-DNA). NPs were prepared by a double emulsification-solvent evaporation technique, using F68 (Pluronic F68, namely Poloxamer 188) as surfactant (not traditional stabilizer PVA), and characterized by morphology, particle size, zeta potential, nuclease, and sonication protection ability, as well as transfection efficiency. Results showed that PPD had a regular spherical shape, with an average diameter of 155 ± 2.97 nm and a zeta potential of −25.6 ± 1.35 mV. PPD could protect plasmid DNA from nuclease degradation and sonication during preparation, while the transfection efficiencies in HepG2 cells and Hela cells were much higher than that of NPs without PLL. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007     

Surface‐modified pliable PDLLA/PCL/β‐TCP scaffolds as a promising delivery system for bone regeneration

Surface‐modified poly(d , l ‐lactide)/polycaprolactone/β‐tricalcium phosphate complex scaffold was fabricated in this study and we hypothesized that pliable and mechanical strong scaffold would be achieved by regulation of ternary compositions; while superficial modification strategy conduced to preserve and controlled‐release of bioactive growth factors. Properties of the composite scaffolds were systematically investigated, including mechanical properties, surface morphology, porosity, wettability, and releasing behavior. Moreover, the representative cytokine, recombinant human bone morphogenetic protein‐2 (rhBMP‐2), was loaded and implanted into muscular pouch of mouse to assess bone formation in vivo. Improved osteogenesis was achieved ascribed to both amplified β‐tricalcium phosphate (β‐TCP) content and retarded initial burst release. Particularly, scaffold doped with hydroxypropyl methylcellulose (HPMC) displayed optimal osteogenic capability. The results indicated that the PDLLA/PCL/β‐TCP complex scaffold along with HPMC‐coating and rhBMP‐2 loading was a promising candidate for bone regeneration. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40951.     

Design and optimization of alginate−chitosan−pluronic nanoparticles as a novel meloxicam drug delivery system

The inflammation and pain associated with osteoarthritis are treated with nonsteroidal anti‐inflammatory drugs (NSAIDs). This treatment is accompanied by several side effects; therefore local intra articular (IA) NSAID injection can be more efficient and safe than systemic administration or topical use. In this study, alginate?chitosan?pluronic nanoparticles were considered as a new vehicle for IA meloxicam delivery. These novel nanoparticles were prepared using an ionotropic gelation method and were optimized for variables such as alginate to chitosan mass ratio, pluronic concentration, and meloxicam concentration using a 3‐factor in 3‐level Box‐Behnken design. To optimize the formulation, the dependent variables considered were particle size, zeta potential, entrapment efficiency, and mean dissolution time (MDT). The nanoparticles morphology was characterized by FESEM and AFM. The potential interactions of the drug‐polymers were investigated by ATR‐FTIR and DSC, and the delivery profile of meloxicam from the nanoparticles was obtained. The average particle size of the optimized nanoparticles was 283 nm, the zeta potential was ?16.9 mV, the meloxicam entrapment efficiency was 55%, and the MDT was 8.9 hours. The cumulative released meloxicam amount from the composite nanoparticles was 85% at pH 7.4 within 96 h. The release profile showed an initial burst release followed by a sustained release phase. The release mechanism was non‐Fickian diffusion. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42241.     

Synthesis and characterization of a new amphiphilic copolymer containing multihydroxyl segments for drug carrier

A new amphiphilic copolymer (copoly‐(MR‐BMA‐HEA‐MAA), PRBHM) containing multihydroxyl segments was designed and synthesized for application in drug carrier. PRBHM can be dissolved in water to form aggregates directly with a critical aggregate concentration (CAC) of 0.0138 mg mL^?1. The chains of PRBHM can be collapsed into hydrophobic globules when pH decreases from neutral to slightly acid condition (pH = 5.0–7.0) in water. Since the hydrophilic hydroxyl group is independent on pH, PRBHM can keep stable both in neutral and slightly acid aqueous solutions. The hydrophobic small molecules such as 5‐(4‐(4‐vinylbenzyloxy) phenyl)‐4,5‐dihydro‐1,3‐diphenyl‐1H‐pyrazole (PY) can be loaded into PRBHM aggregates via ultrasonic treatment in water, and can be internalized into BEL‐7402 cancer cells. The cytotoxicity determination also indicates the good biocompatibility of PRBHM in potential application as a drug carrier. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Investigations of amphiphilic butylglyceryl-functionalized dextran nanoparticles for topical delivery

Toward the development of colloidal systems that can enhance transdermal permeation of hydrophilic actives, a material combining the non-toxic of dextran with alkylglycerols permeation enhancing property has been designed. To this purpose, a range of amphiphilic butylglyceryl dextrans (DEX-OX4) was synthesized via modification with n-butylglycidyl ether with a degree of functionalization in the range 6.3%–35.7%. A reduced viscosity and an increased molecular weight of DEX-OX4 were recorded when compared to the starting material. DEX-OX4 was formulated into nanocarriers and loaded with α-arbutin prior to characterization—the nanoparticles (180–220 nm size) were found to be close-to-spherical, stable at pH 5 and 7, with a loading capacity of 11.7%. Slower release of α-arbutin from the nanoparticles was demonstrated when tested in acidic media. Lack of toxicity at application-relevant concentrations and increased permeation were demonstrated by nanoparticles in vitro results against immortalized skin human keratinocytes cells (HaCaT).     

Amide pectin: A carrier material for colon‐targeted controlled drug release

In order to deliver bioactive components to the colon, an oral colon‐targeted bioadhesive microparticle delivery system based on pectin was developed. Unmodified pectin exhibited a poor hydrophobicity and weak tablet‐crushing strength. Pectin was modified by an amide reaction, which results in a dramatic decrease in water solubility and viscosity, as well as favorable controlled release properties. Amide pectin (AP) were characterized by Fourier transform infrared spectroscopy (FTIR), Nuclear magnetic resonance (¹H‐NMR), and Differential scanning calorimetry (DSC). Results of FTIR and ¹H‐NMR revealed that amide groups were introduced into the pectin molecules; DSC analysis exhibited that the thermal stability of pectin was decreased. An in vitro release assay demonstrated that matrix tablets prepared by AP could deliver bioactive components to the colon when the pectin content and hydrophobicity were properly controlled. The relationship between the structure and in vitro release properties of amide pectin suggests that an optimal tablet structure and composition can be responsible for a suitable BSA release rate. The optimal tablets making conditions were using methylcellulose (MC) as tablet adhesive, amidation reaction time of 60 min, drug loading of 0.008 g and tableting pressure of 8 kg/mm. The results indicated that matrix tablets made by AP exhibited good colon‐targeted drug release. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43697.     

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     

Self-assembled poly(ethylene glycol) methyl ether-grafted gelatin nanogels for efficient delivery of curcumin in cancer treatment

Curcumin (CUR) is a natural active ingredient that attracted much attention for its chemotherapeutic activity against tumors without causing toxicity in healthy cells. However, it has certain limitations for being used in chemotherapy such as low aqueous solubility and hydrolytic instability in the physiological environment. In this study, self-assembled poly(ethylene glycol) methyl ether-grafted gelatin (Gel-mPEG) nanogels were fabricated as delivery systems to improve the applicability of CUR in cancer treatment. CUR-loaded Gel-mPEG nanogels exhibited desired size range, relatively colloidal stability, and provided enhanced CUR stability in aqueous solutions. Especially, they showed significant high CUR loading capacity and better anticancer activity than free CUR as compared to previously reported CUR-loaded nanogels according to the best of our knowledge. Moreover, the in vitro release of CUR from the nanogels was controlled and prolonged up to 96 h. These results demonstrated that Gel-mPEG nanogels are the promising modality for the efficient delivery of CUR in cancer treatment. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47544.     

Preparation and release kinetics of carboxymethyl chitosan/cellulose acetate microspheres as drug delivery system

Carboxymethyl chitosan, a water soluble chitosan derivative, was prepared from chitosan using monochloroacetic acid. Carboxymethyl chitosan/cellulose acetate microspheres (CCM) were prepared using the method of W/O/W and emulsification solvent evaporation as drug delivery system. The CCMs prepared were spherical, free‐flowing, and nonaggregated with the smooth appearance and many small pores on the surface. All CCMs prepared had sustained release efficiency for acetaminophen and the optimal formulation was that carboxymethyl chitosan of 2.0% and 1360 KD. In addition, the release rate of drug from CCMs in dilute hydrochloric acid was much slower than that in phosphate buffer saline (pH 6.8) during 24 h. It is illustrated that the drug loaded in CCMs released slower in simulated gastric fluid than that in simulated intestinal fluid. Furthermore, the drug release data showed better fitness with the first order model which indicated that the drug release from CCMs was depended on the drug concentration in the polymeric networks. And the release of drug from CCMs indicated diffusion‐controlled drug release based on Fickian diffusion and accompanied with anomalous transport (i.e., non‐Fickian diffusion) according to the values obtained from Higuchi model and Peppas models. So it was shown that the CCMs might be an ideal sustained release system for acid‐labile drugs both for the solubility of carboxymethyl chitosan and the release media. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42152.     

Biodegradable polymeric injectable implants for long‐term delivery of contraceptive drugs

Development of injectable, long‐lasting, contraceptive drug delivery formulations, and implants are highly desired to avoid unplanned pregnancies while improving patient compliance and reducing adverse side effects and treatment costs. The present study reports on the fabrication and characterization of two levonorgestrel (LNG) microsphere injectable formulations. Poly(?‐caprolactone) (PCL) with 12.5% and 24% (w/w) LNG were fabricated into microspheres, measuring 300 ± 125 µm, via the oil‐in‐water (o/w) emulsion solvent evaporation technique. Formulations showed sustained drug release up to 120 days. FTIR, XRD, DSC, and TGA confirmed the absence of LNG chemical interaction with PCL as well as its molecular level distribution. The in vitro release of LNG was calculated to be Fickian diffusion controlled and properly characterized. The inclusion of multiple elevated release temperatures allowed for the application of the Arrhenius model to calculate drug release constants and representative sampling intervals, demonstrating the use of elevated temperatures for accelerated‐time drug release studies. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46068.     

Lanolin‐based organogels as a matrix for topical drug delivery

The current study deals with the development of lanolin‐based emulsion gels by hot emulsification method. Bright‐field, phase contrast, and fluorescent micrographs of the gels have shown the uniform distribution of circular water droplets in the formulations. Coalescence of water droplets was observed in gels containing higher proportion of water. Fourier transform infrared spectrophotometric studies indicated absence of Ln‐drug chemical interactions. X‐ray diffraction studies suggested an increase in amorphousness of the gels with the incorporation of water into the gel structure. The salicylic acid (SA), model drug, release from the gels was found to follow Higuchi kinetics. Krossmeyer–Peppas model fitting indicated non‐Fickian release of the drug. As the water content of the gels increased, there was a corresponding increase in the rate of release of the drug. The gels showed non‐Newtonian and thixotropic flow behavior. The gel to sol transition and melting temperatures of the gels were identified by differential scanning calorimetric (DSC) thermal analysis and falling ball method. DSC thermograms indicated an increase in thermal stability with the increase of water content in the gels. The gels showed sufficient spreadability and biocompatibility characteristics to be used as topical formulations. SA loaded gels showed good antimicrobial efficacy against Bacillus subtilis, a Gram‐positive bacterium. Based on the preliminary studies, the developed gels may be regarded as carriers in topical drug delivery. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

A review of the developments of characteristics of PEI derivatives for gene delivery applications

Redox‐active stimuli have gained a great deal of interest as an indicating factor for designing bioresponsive matrices in gene delivery. Hence, a wide range of gene carriers has been designed incorporating the redox‐stimuli characteristics. The most important type of gene carriers is the class of redox responsive polymers. Among them, disulfide incorporated redox‐responsive polyethyleneimine (PEI) and its derivatives, as a result of their outstanding DNA entrapping characteristics and their intrinsic endosomolytic activity, have attracted considerable attention in recent studies. The review presents the main developments of the characteristics of PEI derivatives and their applications in gene delivery. It is found that despite the uniquely stated characteristics, the noncleavable structure of conventional PEI (high molecular weight PEI: 25k), which makes it a nondegradable material, as well as the frequent inclusion of positively charged amino groups, which reduces its blood circulation period, render conventional PEI a very toxic material for gene‐delivery applications. The extremely high cellular toxicity of conventional PEI has restricted its administration for real in‐vivo physiological media. Recent studies have shown that employing low molecular weight PEI cross‐linked by disulfide linkages (SS‐PEI) and assembling low molecular weight disulfide linkages PEI (LMW SS‐PEI) with bio‐detachable anionic groups were two successful approaches for increasing bioavailability of the PEI‐based gene carriers, while keeping outstanding cellular transfection. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42096.     

Near‐infrared‐active and pH‐responsive fluorescent polymer‐integrated hybrid graphene oxide nanoparticles for the detection and treatment of cancer

Hybrid nanoparticles for theragnosis have great potentiality to bring desire functionalities in one integrated system. The development of bioimaging guided photothermal therapy (PTT) is pivotal in optimizing cytotoxic cancer therapy. We report near‐infrared (NIR)‐active and pH‐responsive fluorescent, catechol‐conjugated, reduced graphene oxide (rGO)‐anchored hybrid nanoparticles that can sharply increase the photothermal heat in response to NIR exposure and exhibit pH‐dependent fluorescence emission for the detection of tumor areas without causing cell toxicity. The optoelectronic absorption property of poly(3,4‐ethylenedioxythiophene) [PEDOT]:dopamine‐conjugated poly(4‐styrenesulfonate‐co‐maleic acid) [D‐PSM] and 3′,4′‐dihydroxyacetophenone/boron‐dipyrromethene [CCDP/BODIPY]‐quaternized polyethylene glycol grafted poly(dimethylaminoethyl methacrylate) (C/B‐PgP) present in this hybrid nanoparticles resulted in efficient photothermal conversion with pH‐tunable fluorescence that exerted sufficient photothermal cytotoxicity to cancer cells. The in vitro cellular uptake was measured by confocal laser scanning microscopy, allowing the therapeutic efficiency and bioimaging effects to be explored. We expect that the broad optical absorption property of PEDOT:D‐PSM with BODIPY‐conjugated polymers on rGO sheets would get tremendous attraction in this enormous rising PTT with cancer detectable biomarker. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43791.     

Thermal,electrical, and mechanical properties of tween 80/span 80–based organogels and its application in iontophoretic drug delivery

The present study describes the preparation and characterization of the Tween 80/Span 80 and sunflower oil–based organogels. Organogels were characterized using microscopy, X‐ray diffraction, thermal, mechanical, and electrical techniques. The properties were found to be dependent on the proportion of the water : surfactant mixture. The in vitro drug release studies were performed under electrical potential. The drug release in the presence of electrical current was compared with the passive drug release. The drug release from the organogels followed the zero‐order kinetics suggesting diffusion mediated release. The preliminary results suggested that the organogels may be used as drug carriers in iontophoretic drug delivery. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41419.     

Hydrophobic and hydrophilic modifications of polyethylenimine towards gene delivery applications

Non-viral gene delivery has emerged as a promising approach for therapy in cancer treatment. Polyethylenimine (PEI) is a prominent transfecting agent, but due to toxicity and poor hemocompatibility, its usage for in vivo applications is limited. However, modification of PEI with different chemical groups can lead to conjugates with good transfection efficiency and better cytocompatibility. In this study, the efficiency of PEI derivatives, namely, PEI succinate (PEIS), PEI lauryl succinate (PEILS), PEI laurate (PEIL) was analyzed for gene delivery applications. Apart from biophysical characterization such as size, zeta potential, nanoplex stability and buffering capacity, cellular internalization, polymer trafficking and p53 transgene expression in C6 cell lines were also investigated. The results indicate that PEI conjugated with lauryl succinate act as better transfecting agent with high efficiency compared to other derivatives, and such balanced hydrophilic-hydrophobic modification of PEI can render it to be a cytocompatible and effective nucleic acid delivery system.     

Polyvinyl alcohol‐polyethylene oxide‐carboxymethyl cellulose membranes for drug delivery

The purpose of this research was to develop blends of poly(vinyl alcohol) (PVA)‐poly(ethylene oxide) (PEO) and carboxymethyl cellulose (CMC) by two approaches: solvent casting and freeze‐drying to develop membranes for various biomedical applications. The PVA/PEO/CMC blends in different compositions of 90/10/20, 80/20/20, 70/30/20, 60/40/20, and 50/50/20 were prepared and were coated on polyester (PET) nonwoven fabric and were subsequently freeze‐dried (FD). The influence of PEO concentration on the blend membranes was investigated and characterized by X‐ray diffraction (XRD), differential scanning calorimetry, and attenuated total reflectance‐fourier transform infra‐red (ATR–FTIR) techniques. The water vapor transmission rate (WVTR), swelling behavior, and surface morphology of the FD membranes was also investigated. It was observed that an increase of PEO concentration in blends makes the membranes more fragile. However, the coating of this blend on PET fabric helps in developing the stable membrane. Swelling of the membranes decreased with the increase in the PEO concentration. XRD showed decrease in crystallinity with increase in concentration of PEO. Morphological studies showed a highly porous structure with interconnected pores. The total porosity of the membranes was found to be in the range 89–92%. The FD membranes were found to have WVTR in the range 2000–3000 g/m²/day. A model drug, ciprofloxacin hydrochloride was also incorporated in the matrix and drug release was studied. The antimicrobial nature of the membranes was monitored against E. coli by zone of inhibition method. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Palm oil‐based organogels and microemulsions for delivery of antimicrobial drugs

This study has been designed to develop palm oil (PO) based organogels using span 80/tween 80 mixture (OG) as a gelator system by fluid‐filled structure mechanism. The results suggested formation of organogels, emulsions, and microemulsions as the proportions of PO, OG and water were varied. The emulsions were found to be thermodynamically unstable as compared to the organogels and the microemulsions. Accelerated thermal stability test suggested that all the microemulsions and the organogels of only eight compositions were stable. The organogels showed viscoelastic property while the microemulsions showed viscous flow behavior. Both the organogels and the microemulsions were found to be highly hemocompatible and nonirritant. The antimicrobial efficiency of the ciprofloxacin HCl‐loaded formulations showed equivalent efficiency as compared to marketed formulations. The rates of drug release from the organogels were found to be relatively slower as compared to the microemulsions. The preliminary studies suggested that the developed organogel and microemulsion‐based formulations may be tried for topical delivery of antimicrobials. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2014 , 131, 39979.     

Complex aggregates formed with a hyperbranched polyglycerol derivative for drug delivery

An amphiphilic hyperbranched polyglycerol derivative (HPG‐C18) was synthesized by the anionic ring‐opening copolymerization with glycidol and 1,2‐epoxyloctadecane as the monomers. This hyperbranched polymer formed large complex aggregates as confirmed by dynamic light scattering and transmission electron microscopy tests. Because of its amphiphilic properties, HPG‐C18 was explored to load hydrophobic docetaxel, a clinical antitumor drug, and deliver it into breast cancer cell line (MCF‐7) cells. To investigate the application of the aggregates in drug delivery, blood compatibility was studied by hemolysis analysis, red blood cell observation, and thromboelastography assay. These results indicate that HPG‐C18 inhibited MCF‐7 proliferation effectively with good blood compatibility, and this suggested a potential application in tumor therapy. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 42895.     

Preparation of zinc-coordinated-DPA functionalized polyesters for gene condensation

Cationic polyesters have been widely utilized as efficient gene delivery carriers. Their ability in binding genes was majorly based on the electrostatic effect between the positive charges of polymers and the negatives charges of genes. It has been well known that large numbers of positive charges on the polymers would lead to undesired toxicity although strong gene binding capability. It was of great interest to developed a polymer with reduced positive charges while enhanced gene condensation ability. In this work, a library of polyesters functionalized by zinc-coordinated-dimethylpyridinium amine (DPA-Zn) have been successfully prepared by the polycondensation method starting from dimethyl 1,3-acetonedicarboxylate and 10 diols, followed by the post-modification using dimethylpyridinium amine and zinc nitrate. The post-modification efficiency was systemically evaluated and the optimized functionalization efficiency could reach around 50%. The gene condensation ability of the targeting polymers was also evaluated using gel retardation assay and dynamic light scatting. The results indicated that DPA-Zn functionalized polyesters could bind gene into nanocomplexes with the sizes around 200 nm.