Use Of Drug Delivery Systems Research Articles

Chitosan-based Polymer Matrix for Pharmaceutical Excipients and Drug Delivery.

The development of innovative drug delivery systems, versatile to different drug characteristics with better effectiveness and safety, has always been in high demand. Chitosan, an aminopolysaccharide, derived from natural chitin biomass, has received much attention as one of the emerging pharmaceutical excipients and drug delivery entities. Chitosan and its derivatives can be used for direct compression tablets, as disintegrant for controlled release or for improving dissolution. Chitosan has been reported for use in drug delivery system to produce drugs with enhanced muco-adhesiveness, permeation, absorption and bioavailability. Due to filmogenic and ionic properties of chitosan and its derivative(s), drug release mechanism using microsphere technology in hydrogel formulation is particularly relevant to pharmaceutical product development. This review highlights the suitability and future of chitosan in drug delivery with special attention to drug loading and release from chitosan based hydrogels. Extensive studies on the favorable non-toxicity, biocompatibility, biodegradability, solubility and molecular weight variation have made this polymer an attractive candidate for developing novel drug delivery systems including various advanced therapeutic applications such as gene delivery, DNA based drugs, organ specific drug carrier, cancer drug carrier, etc.

Multicomponent self nano emulsifying delivery systems of resveratrol with enhanced pharmacokinetics profile

Resveratrol is a drug with high potential for clinical application based on experimental models. Though, resveratrol translation to clinical use has not been successful yet due to its poor pharmacokinetics, related to poor solubility and fast metabolism. The use of drug delivery systems, namely self-emulsifying drug delivery systems (SEDDS), may be a viable strategy to overcome the poor in vivo performance of resveratrol. In this work, a rational development of two different ternary SEDDS was conducted. Experimental data showed that quantitative variations on SEDDS composition impacted dispersion and robustness to dilution of SEDDS, as well as loading capacity and droplet size. Formulations composed of Lauroglycol® 90/Labrasol®/Capryol® PGMC (12.5/75.0/12.5) (Lau/Lab/Cap) and Tween® 80/Transcutol®/Imwitor® 742 (33.3/33.3/33.3) (T80/Trans/Imw) featured improved performance and were selected for further studies. T80/Trans/Imw formulation yield faster emulsification and originated smaller droplet size, with lower cumulative percentile of 90% of particles (D90) (below 200 nm), as compared to the than Lau/Lab/Cap formulation. Higher resveratrol permeation rate was observed in Caco-2 cell monolayer permeability studies for both formulations as compared to the free drug. Reduction of the metabolization and/or efflux of resveratrol was also noticed in the case of SEDDs, as suggested by the increased recovery of total drug. Plasmatic drug concentrations in rats observed after oral gavage indicate that both formulations provided faster resveratrol absorption than free drug, resulting in shorter Tmax values (30 min vs. 2 h). No statistically significant differences were observed for AUC0-t values of both formulations and the free drug. Still, Cmax for the Lau/Lab/Cap SEDDs formulation was 2-fold higher than for the free drug. These findings suggest that SEDDS can increase resveratrol solubility and reduce its metabolization, resulting in an overall improvement of its oral pharmacokinetics profile.

Pharmacokinetic and Pharmacodynamic Properties of Drug Delivery Systems.

The use of drug delivery systems (DDS) is an attractive approach to facilitate uptake of therapeutic agents at the desired site of action, particularly when free drug has poor pharmacokinetics/biodistribution (PK/BD) or significant off-site toxicities. Successful translation of DDS into the clinic is dependent on a thorough understanding of the in vivo behavior of the carrier, which has, for the most part, been an elusive goal. This is, at least in part, due to significant differences in the mechanisms controlling pharmacokinetics for classic drugs and DDSs. In this review, we summarize the key physiologic mechanisms controlling the in vivo behavior of DDS, compare and contrast this with classic drugs, and describe engineering strategies designed to improve DDS PK/BD. In addition, we describe quantitative approaches that could be useful for describing PK/BD of DDS, as well as critical steps between tissue uptake and pharmacologic effect.

Sustained Releasing of Methotrexate from Injectable and Thermosensitive Chitosan-Carbon Nanotube Hybrid Hydrogels Effectively Controls Tumor Cell Growth.

Injectable thermosensitive hydrogels have been widely investigated for drug delivery systems. Chitosan (CH) is one of the most abundant natural polymers, and its biocompatibility and biodegradability make it a favorable polymer for thermosensitive hydrogel formation. The addition of nanoparticles can improve its drug release behavior, remote actuation capability, and biological interactions. Carbon nanotubes (CNTs) have been studied for the use in drug delivery systems, and they can act as drug delivery vehicles to improve the delivery of different types of therapeutic agents. In this work, carbon nanotubes were incorporated into a thermosensitive and injectable hydrogel formed by chitosan and β-glycerophosphate (β-GP) (CH−β-GP–CNTs). The hybrid hydrogels loaded with methotrexate (MTX) were liquid at room temperature and became a solidified gel at body temperature. A number of tests including scanning electron microscopy, Fourier transform infrared spectroscopy, Raman spectroscopy, and X-ray diffraction were utilized to characterize the MTX-loaded CH−β-GP–CNT hybrid hydrogels. The cell viability (alamarBlue) assay showed that hydrogels containing CNT (0.1%) were not toxic to the 3T3 cells. In vitro MTX release study revealed that CNT-containing hydrogels (with 0.1% CNT) demonstrated a decreased MTX releasing rate compared with control hydrogels without CNT. The cultured MCF-7 breast cancer cells were used to evaluate the efficacy of CH−β-GP–CNT hybrid hydrogels delivering MTX on the control of tumor cell growth. Results demonstrated that CNT (0.1%) in the hydrogel enhanced the MTX antitumor function. Our study indicates that a thermosensitive CH−β-GP–CNT hybrid hydrogel can be used as a potential breast cancer therapy system for controlled delivery of MTX.

Starch nanoparticles in drug delivery: A review.

The uptake and specificity of drugs and the bioavailability of poorly soluble drugs has been improved by means of targeted drug delivery using nanoparticles. Many platforms have been used for nanoparticulate drug delivery and these include liposomes, polymer conjugates, metallic nanoparticles, polymeric micelles, dendrimers, nanoshells, and protein and nucleic acid-based nanoparticles. Starch is the 2nd most abundant natural polymer and has found wide use in drug delivery systems as binder, disintegrant and filler. However, its application is limited by the poor functional properties of native starch. Starch nanocrystals of different shapes and sizes can be obtained based on the starch origin and isolation process involved. Nanocrystals with varying morphology have been reported; from nanocrystals of platelet-like shaped waxy maize starch with 5-7 nm thickness and 15-40 nm diameters, to those with round and grape-like shape from potato starch granules, with sizes ranging from 40 nm to 100 nm. This review describes different methods of obtaining starch nanoparticles, their modification and application in drug delivery.

Aggregation behavior of self-assembled nanoparticles made from carboxymethyl-hexanoyl chitosan and sodium dodecyl sulphate surfactant in water

Biopolymers can be used to produce nano-objects in solution and they are generally of low cost and biocompatible. However, they commonly have low kinetic stability and form aggregates with a broad particle size distribution, characteristics that hinder their use in drug delivery systems. Herein, we report the thermodynamics and mechanisms underlying the formation of nanostructures through the self-assembly of carboxymethyl-hexanoyl chitosan (ONCHC) and the effect of the presence of the surfactant sodium dodecyl sulfate (SDS). The pre- and post-aggregation regimes were monitored using several techniques and indicated that self-assembly is thermodynamically favorable. The presence of SDS decreased the hydrodynamic radius and surface charge of the SDS-ONCHC nanoaggregates and increased the kinetic stability in aqueous solution over a period of 150 days. The SDS-ONCHC interaction is driven mainly by a hydrophobic effect and the addition of SDS increases the number and strength of the hydrophobic domains, where the integral enthalpy change for the aggregate formation is −2.11 kJ mol−1.

POLY(HYDROXYBUTYRATE-CO-HYDROXYVALERATE) MICRONIZATION BY SOLUTION ENHANCED DISPERSION BY SUPERCRITICAL FLUIDS TECHNIQUE

ABSTRACT Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) is a biodegradable polymer used for a wide range of applications, especially in biomedical and food industry, for which bioactive compound encapsulation is noteworthy. This work aimed to micronize PHBV by Solution Enhanced Dispersion by Supercritical Fluids technique and evaluate possible changes in polymer crystallinity. A 23 Central Composite Design with 3 central points was used to analyze the influence of pressure, temperature and PHBV concentration on particle size produced. Micronized particles were mostly spherical with sizes from 210 to 720 nm, and free of organic solvents. PHBV crystallinity degree was approximately 20% higher when polymer was processed at 8 MPa compared to that processed at 10 and 12 MPa, as well as to the raw polymer. Results suggest versatility in PHBV application according to SEDS process parameters and the possibility of its use in drug delivery systems.

Temperature–Light Dual‐Responsive Au@PNIPAm Core‐Shell Microgel‐Based Optical Devices

AbstractAu nanoparticle (AuNP) core particles coated with a poly(N‐isopropylacrylamide) (pNIPAm) shell (Au@pNIPAm) are synthesized by seed mediated free radical polymerization. Subsequently, a temperature–light‐responsive photonic device is fabricated by sandwiching the Au@pNIPAm particles between two thin layers of Au. The optical device exhibits visual color and characteristic multipeak reflectance spectra, where peak position is primarily determined by the distance between two Au layers. Dual responsivities of the photonic device are achieved by combining the photothermal effect of AuNPs core (localized surface plasmon resonance (LSPR) effect) and the temperature responsivity of the pNIPAm shell. That is, the pNIPAm shell collapses as the temperature is increased above pNIPAm's lower critical solution temperature, either by direct heat input or heat generated by AuNPs' LSPR effect. To investigate the effect of AuNPs distribution in the microgels on the devices' photothermal responsivity, the Au@pNIPAm microgel‐based etalon devices are compared with that fabricated by AuNP‐doped pNIPAm‐based microgels; in terms of response kinetics and optical spectrum homogeneity. The uniform Au@pNIPAm microgel‐based devices show a fast response and exhibit a comparatively homogeneous spectrum over the whole slide. These materials can potentially find use in drug delivery systems, active optics, and soft robotics.

Release behavior of a polyanion‐crosslinked chitosan‐poly(N‐isopropylacrylamide) gel thermoresponsive material

ABSTRACTA novel type of temperature‐responsive hydrogel with sensitive release performance of an encapsulated compound was obtained. The temperature‐responsive hydrogel with a sensitive state change between 32 °C and 29 °C was prepared by physically crosslinking chitosan with a polyanion of tripolyphosphate and linear poly(N‐isopropylacrylamide) (PNIPAAm). Cyanocobalamin was used as a model drug and was encapsulated in the prepared hydrogel. The swelling ratio and release behavior of cyanocobalamin were evaluated. Hydrogels containing 3.0% chitosan and 3.0% PNIPAAm had the best swelling ratio and the maximum amount of released encapsulated cyanocobalamin. The amount of released cyanocobalamin was quantified at 25 °C and 40 °C to evaluate the release behavior. The encapsulated cyanocobalamin remained within the hydrogels at 25 °C and was rapidly released at 40 °C. After 1 min at 40 °C, the released amount was approximately 50% of the encapsulated cyanocobalamin. The temperature‐responsive hydrogels obtained have good performance for use in drug delivery systems. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46732.

Acute toxicity study of a polysaccharide based hydrogel from linseed for potential use in drug delivery system

ABSTRACT Linseed hydrogel (LSH) was evaluated by acute toxicity for its potential application in oral drug delivery design. White albino mice and rabbits were divided in four groups (I-IV) and different doses of LSH (1, 2 and 5 g/kg body weight) were given except to the control group (I) that was left untreated. Rabbits were monitored for eye irritation, acute dermal toxicity and primary dermal irritation, whereas, body weight, food and water consumption, hematology and clinical biochemistry, gross necropsy and histopathology of vital organs were scrutinized in mice. LSH was considered safe after eye irritation test as no adverse signs or symptoms were seen in the eye. In dermal toxicity and irritation study, skin of treated rabbits was found normal in color without any edema or erythema. After oral administration, there was no sign of any abnormalities in treated group animals (II-IV). The hematology and clinical biochemistry of treated group animals was comparable with the control group. Histopathology of vital organs has not shown any lesion or abnormalities. In the light of these outcomes, it can be concluded that LSH is not a hazardous biomaterial and could be incorporated as an excipient in oral and dermal preparations.

Primary biocompatibility tests of poly(lactide-co-glycolide)-(poly-L-orithine/fucoidan) core-shell nanocarriers.

Layer-by-layer (LbL) self-assembly is the technology used in intermolecular static electricity, hydrogen bonds, covalent bonds and other polymer interactions during film assembling. This technology has been widely studied in the drug carrier field. Given their use in drug delivery systems, the biocompatibility of these potential compounds should be addressed. In this work, the primary biocompatibility of poly(lactide-co-glycolide)-(poly-L-orithine/fucoidan) [PLGA-(PLO/fucoidan)] core–shell nanoparticles (NPs) was investigated. Atomic force microscopy revealed the PLGA-(PLO/Fucoidan)4 NPs to be spherical, with a uniform size distribution and a smooth surface, and the NPs were stable in physiological saline. The residual amount of methylene chloride was further determined by headspace gas chromatography, in which the organic solvent can be volatilized during preparation. Furthermore, cell viability, acridine orange/ethidium bromide staining, haemolysis and mouse systemic toxicity were all assessed to show that PLGA-(PLO/fucoidan)4 NPs were biocompatible with cells and mice. Therefore, these NPs are expected to have potential applications in future drug delivery systems.

Effect of detonation nanodiamond surface composition on physiological indicators of mitochondrial functions

For the first time, an effect of detonation nanodiamonds (NDs) with different surface compositions on the main functional characteristics of isolated rat liver mitochondria was studied. The response of membrane potential, calcium retention capacity, and redox state of pyridine nucleotides have been monitored upon the administration of NDs functionalized with carboxyl, hydroxyl, amine, hydrogen, and chlorine surface groups. Hydrogenated and chlorinated NDs caused reduction of the membrane potential and calcium retention capacity of mitochondria. An aminated ND caused an even greater decrease in calcium retention capacity (at a concentration of 0.75 mg/ml), reducing it to 65% of the control. The use of cyclosporine A prevented a decrease in membrane potential and calcium retention capacity indicating the induction of non-specific mitochondrial membrane pores during the NDs incubation with mitochondria. Hydrogenated and chlorinated NDs had no significant effect on the redox state of mitochondrial pyridine nucleotides. Other NDs studied had no effects on functional characteristics of mitochondria, even at high concentrations (up to 1.5 mg/ml). High activity of chlorinated and hydrogenated NDs may be due to the greater hydrophobicity of their surface and its interaction with mitochondrial pores components. Thus, isolated rat liver mitochondria can be used as a biomodel for initial testing of ND samples to assess the possibility of their use in drug delivery systems.

MPEG-co-PCL nanoparticles: The influence of hydrophobic segment on methotrexate drug delivery

The use of drug delivery system based on polymeric nanoparticles (PNP) has been investigated due to its capacity to carrier hydrophobic drugs across natural barriers and to access new sites in the human body to release drugs at different tissues or cells. In the present work, polyethylene glycol monomethyl ether – co – polycaprolactone copolymer (mPEG-co-PCL) was synthesized by ring opening polymerization of the ε-caprolactone in the presence of polyethylene glycol monomethyl ether (mPEG) as a macroinitiator and tin(II) 2-ethylhexanoate (Sn (Oct)2), as a catalyst. On this step, three syntheses were realized to increase the polycaprolactone (PCL) hydrophobic segment of the copolymer. PNP of mPEG-co-PCL were obtained by emulsion – solvent evaporation method, which the surfactant concentration (Tween80®), cosurfactant (dodecane) and water/oil ratio were studied to control the size of nanoparticles. The PNP ability to loading and releasing drugs was evaluated with methotrexate (MTX), a drug commonly used for cancer treatment. The copolymers were synthesized with different chain length, increasing PCL hydrophobic segment, resulting in molecular weight between 2,000 to 13,000 g mol−1. The lowest hydrodynamic diameter (79.5 nm) of PNP was obtained with a solution of 1 × 10-4 mol L−1 Tween80® solution and 500 u L of dodecane. The water/oil ratio showed insignificant influence on hydrodynamic diameter, according to factorial design results. The copolymers showed a loading efficiency of MTX higher than 80.0%. The MTX releases from mPEG-co-PCL platform had occurred by anomalous transport mechanism in the first hours. After 16 h the release rate of MTX decrease drastically and its behavior was governed by PCL degradation process. As PCL ratio is increased on copolymer, the drug release decrease, suggesting an interaction of MTX with PNP hydrophobic segment. Thus, the MTX release could be controlled by copolymer chain length through hydrophilic and hydrophobic segment composition ratio, being a good candidate for hydrophobic drug delivery systems.

Insulating chitosan/casein multilayers on corona charged polylactic acid substrates

The influence of the structure and physico-chemical properties of chitosan/casein multilayer films on their potential use for drug delivery systems was investigated. The multilayer films were prepared using layer-by-layer self-assembly, whereby chitosan and casein were deposited onto poly(lactic acid) substrates pretreated with either a positive or a negative corona. The corona discharge system consisted of a corona electrode, a grounded plate and a grid. The deposition was studied by ATR FT-IR, AFM, and surface energy measurements. ATR FT-IR spectra proved the formation of polyelectrolyte chitosan — casein complexes. The increasing content of chitosan and casein with increasing number of bilayers was further confirmed by XPS analysis. The surface topography was examined by AFM and the average roughness was evaluated. A comparative analysis of the experimental results was performed and the most appropriate substrate corona treatment for the irreversible binding of the chitosan/casein polyelectrolytes was determined.

Preparation and Characterization of Electrostatically Crosslinked Polymer⁻Liposomes in Anticancer Therapy.

pH-sensitive polymer–liposomes can rapidly release their payloads. However, it is difficult to simultaneously achieve stability and pH-responsiveness in the polymer–liposomes. In this study, stable and pH-sensitive crosslinked polymer–liposomes were fabricated through electrostatic interactions. The pH-sensitive copolymer methoxy poly(ethylene glycol)-block-poly(methacrylic acid)-cholesterol (mPEG-b-P(MAAc)-chol) and crosslinking reagent poly(ethylene glycol) with end-capped with lysine (PEG-Lys2) were synthesized and characterized. At physiological conditions, the pH-sensitive copolymers were anionic and interacted electrostatically with the cationic crosslinker PEG-Lys2, forming the electrostatically-crosslinked polymer–liposomes and stabilizing the liposomal structure. At pH 5.0, the carboxylic groups in mPEG-b-P(MAAc)-chol were neutralized, and the liposomal structure was destroyed. The particle size of the crosslinked polymer–liposomes was approximately 140 nm and the polymer–liposomes were loaded with the anticancer drug doxorubicin. At pH 7.4, the crosslinked polymer–liposomes exhibited good stability with steady particle size and low drug leakage, even in the presence of fetal bovine serum. At pH 5.0, the architecture of the crosslinked polymer–liposomes was damaged following rapid drug release, as observed by using transmission electron microscopy and their apparent size variation. The crosslinked polymer–liposomes were pH-sensitive within the endosome and in the human breast cancer cells MDA-MB-231, as determined by using confocal laser scanning microscopy. The intracellular drug release profiles indicated cytotoxicity in cancer cells. These results indicated that the highly-stable and pH-sensitive electrostatically-crosslinked polymer–liposomes offered a potent drug-delivery system for use in anticancer therapies.

Potential doxorubicin delivery system based on magnetic gelatin microspheres crosslinked with sugars

Abstract The preparation and characterization of magnetic microspheres based on gelatin for use in drug delivery systems are reported. Sugars were employed as crosslinking agents and type A gelatin and type B gelatin were compared to prepare microspheres by water-in-oil emulsion. The influence of gelatin and sucrose concentration, temperature and stirring speed on microbeads’ characteristics was studied. The gelatin concentration and stirring speed were the parameters directly associated with the particle sizes. We found no relevant difference between the use of type A and type B gelatin. In addition, the gelatin crosslinking study revealed that sucrose is not a crosslinking agent but fructose can crosslink the protein chains when the reaction medium has pH 9. The size of the microspheres varied from 5 to 60 μm as measured by optical microscopic images. Doxorubicin adsorption and release were successfully performed using the microspheres crosslinked with fructose under the action of an external magnetic field. It was observed that the microspheres absorbed 69% of the doxorubicin that was in solution. After 24 h, about 45% of the DOX was displaced from microspheres to saline medium in the free form in the solution.

The Effects of Graphene Oxide and Partially Reduced Graphene Oxide on Staphylococcus aureus, Dermal Fibroblasts, and Keratinocytes

ABSTRACTGraphene and graphene oxide are being investigated for use in drug delivery systems, bioimaging, and antimicrobial applications. However, their effects, if any, on healthy cells need to be established before they can be deemed safe for therapeutic use. This research tested whether graphene oxide (GO) and/or partially reduced graphene oxide (pRGO) exhibit antimicrobial properties on Staphylococcus aureus; and also examined the growth and proliferation of dermal fibroblasts and keratinocytes in media modified with graphene oxide or partially reduced graphene oxide. Staphylococcus aureus was able to proliferate in both GO and pRGO- modified growth media as well as on gelatin made with GO and pRGO solutions. Both GO and pRGO increased dermal fibroblast doubling time and displayed lower cell counts compared to the control, with pRGO exerting a more pronounced effect than GO. After 4 days of keratinocyte incubation, GO and pRGO showed cell counts 75-80% less than the control. Cell counts of test samples dropped even lower by day 5 while the control cell count increased, suggesting that more investigation into the properties as well as the safety of graphene and its derivatives needs to be done before it is implemented for medical applications.

The Role of Minimally Invasive Glaucoma Surgery Devices in the Management of Glaucoma.

SIGNIFICANCENoncompliance is a problem affecting glaucoma patients. Approaches to improve adherence include the use of drug-delivery systems and safer forms of surgery. Minimally invasive glaucoma surgery (MIGS) has reduced complications, particularly in combination with cataract surgery, and with its good intraocular pressure (IOP) reduction may reduce or eliminate glaucoma medications.Glaucoma is a progressive disease and a leading cause of irreversible blindness. Elevated IOP is the most important risk factor, but effective medical management is dependent on patient adherence. This review summarizes the adherence problem in glaucoma and the efforts, including MIGS, to provide effective IOP control that is not dependent on patient compliance.The current understanding of patient adherence to pharmacological treatment of glaucoma is discussed including the challenges facing glaucoma patients. Historical approaches to providing IOP control in a sustained and reliable way are presented culminating in a review of the burgeoning use of MIGS devices.It is estimated that, in the United States, 27% of prescriptions written, across all medications, are not filled or are filled but not taken. For ocular hypotensive medications, even when filled, a large percentage (which varies widely by study) are not instilled as prescribed. To address this problem, methods for sustained drug delivery have been and continue to be developed, as well as surgical and laser approaches. Most recently, MIGS devices have gained popularity because of the ease of implantation during cataract surgery, favorable safety profile, and the possibility for effective and long-lasting IOP lowering, as well as the reduction or elimination of need for IOP-lowering medication.Poor adherence to treatment is relatively common among glaucoma patients and is associated with progression of disease. Recommending MIGS implantation during cataract surgery may offer optometrists a valuable treatment option in managing glaucoma patients, particularly where good adherence is in doubt.

Reducible disulfide poly(beta-amino ester) hydrogels for antioxidant delivery

Recently, biomaterials have been designed to contain redox-sensitive moieties, such as thiols and disulfides, to impart responsive degradation and/or controlled release. However, due to the high sensitivity of cellular redox-based systems which maintain free-radical homeostasis (e.g. glutathione/glutathione disulfide), if these biomaterials modify the cellular redox environment, they may inadvertently affect cellular compatibility and/or oxidative stress defenses. In this work, we hypothesize that the degradation products of a poly(β-amino ester) (PBAE) hydrogel formed with redox sensitive disulfide (cystamine) crosslinking could serve as a supplement to the environmental cellular antioxidant defenses. Upon introduction into a reducing environment, these disulfide-containing hydrogels cleave to present bound-thiol groups, yet remain in the bulk form at up to 66 mol% cystamine of the total amines. By controlling the molar fraction of cystamine, it was apparent that the thiol content varied human umbilical vein endothelial cell (HUVEC) viability IC50 values across an order of magnitude. Further, upon introduction of an enzymatic oxidative stress generator to the cell culture (HX/XO), pre-incubated thiolated hydrogel degradation products conferred cellular and mitochondrial protection from acute oxidative stress, whereas non-reduced disulfide-containing degradation products offered no protection. This polymer may be an advantageous implantable drug delivery system for use in acute oxidative stress prophylaxis and/or chronic oxidative stress cell therapies due to its solid/liquid reversibility in a redox environment, controlled thiolation, high loading capacity through covalent drug-addition, and simple post-synthesis modification which bound-thiols introduce. Statement of SignificanceIn this work, we demonstrate a unique property of disulfide containing degradable biomaterials. By changing the redox state of the degradation products (from oxidized to reduced), it is possible to increase the IC50 of the material by an order of magnitude. This dramatic shift is linked directly to the oxidative stress response of the cells and suggests a possible mechanism by which one can tune the cellular response to degradable biomaterials.

Design, Optimization Process and Efficient Analysis for Preparation of Copolymer-Coated Superparamagnetic Nanoparticles

Magnetic nanoparticles (MNPs) are very important systems with potential use in drug delivery systems, ferrofluids, and effluent treatment. In many situations, such as in biomedical applications, it is necessary to cover inorganic magnetic particles with an organic material, such as polymers. A superparamagnetic nanocomposite Fe3O4/poly(maleic anhydride-co-acrylic acid) P(MAH-co-AA) with a core/shell structure was successfully synthesized by a dispersion polymerization route. Iron oxide nanoparticles were used as a core, and P(MAH-co-AA) as a shell was covered on the surface of the Fe3O4 magnetic nanoparticles. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) showed that the Fe3O4/P(MAH-co-AA) magnetic nanocomposite were highly uniform in size and cubic shape with the average size about 17.06 nm. X-ray diffraction confirmed magnetite cores and also indicated that the binding process did not change the phase of Fe3O4. Vibrational sample magnetometer (VSM) revealed the nanoparticles were superparamagnetic and the saturation magnetization was 83.6 and 46.6 emu g-1 for pure Fe3O4 and composite nanoparticles, respectively. Measurements by VSM also showed that the degree of saturation magnetization increased with increasing iron oxide concentration from 1% to 7 wt % of Fe3O4.