Xanthan-g-poly(acrylamide): Microwave-assisted synthesis,characterization and in vitro release behavior

Xanthan-g-poly(acrylamide) was synthesized employing microwave-assisted and ceric-induced graft copolymerization, and was characterized by FT-IR, DSC, XRD and SEM studies. Matrix tablets of diclofenac sodium were formulated using graft copolymer as the matrix by direct compression technique. Release behavior of the graft copolymer was evaluated using USP type-II dissolution apparatus in 900 ml of phosphate buffer (pH 6.8), maintained at 37 °C and at 50 rpm. Microwave-assisted grafting provided graft copolymer with higher % grafting in a shorter time in comparison to the ceric-induced grafting. The % grafting was found to increase with the increase in the power of microwave and/or time of exposure. The matrix tablets were found to release the drug by zero-order kinetics, and the faster release of drug was observed from the graft copolymer matrix as compared to the xanthan gum matrix. It was observed that grafting reduces the swelling, but increases the erosion of xanthan gum.     

Preliminary Investigation on the Development of Diltiazem Resin Complex Loaded Carboxymethyl Xanthan Beads

The objective of this study was to develop a multiunit sustained release dosage form of diltiazem using a natural polymer from a completely aqueous environment. Diltiazem was complexed with resin and the resinate-loaded carboxymethyl xanthan (RCMX) beads were prepared by interacting sodium carboxymethyl xanthan (SCMX), a derivatized xanthan gum, with Al⁺³ ions. The beads were evaluated for drug entrapment efficiency (DEE) and release characteristics in enzyme free simulated gastric fluid (SGF, HCl solution, pH 1.2) and simulated intestinal fluid (SIF, USP phosphate buffer solution, pH 6.8). Increase in gelation time from 5 to 20 min and AlCl₃ concentration from 1 to 3% decreased the DEE respectively from 95 to 79% and 88.5 to 84.6%. However, increase in gum concentration from 1.5 to 2.5% increased the DEE from 86.5 to 90.7%. The variation in DEE was related to displacement of drug from the resinate by the gel forming Al⁺³ ions. While 75–82% drug was released in 2 h in SGF from various beads, 75 to 98% drug was released in 5 hour in SIF indicating the dependence of drug release on pH of dissolution media. Although the beads maintained their initial integrity throughout the dissolution process in both media, as evident from scanning electron microscopic studies, the faster release in SGF was accounted for higher swelling of the beads in SGF than in SIF. When release data (up to 60%) was fitted in power law expression, the drug release was found to be controlled by diffusion with simultaneous relaxation phenomena.     

Synthesis and characterization of superparamagnetic nanoparticles coated with carboxymethyl starch (CMS) for magnetic resonance imaging technique

Magnetic nanoparticles have been proposed for use as biomedical purposes to a large extent for several years. The development of techniques that could selectively deliver drug molecules to the diseased site, without a concurrent increase in its level in healthy tissues, is currently one of the most active areas of cancer research. The conjugate carboxymethyl starch (CMS)/SPIO nanoparticles were prepared by chemical reaction. Several parameters including the drug/polymer ratios in range of 1:14 were examined to optimize formulation. The size distribution and morphology of nanoparticles and in vitro release profile in phosphate buffer medium (pH 7.4) during 12 h were then investigated. The magnetic NPs prepared in this study were spherical with a relatively mono-dispersed size distribution. The conjugate carboxymethyl starch (CMS)/SPIO nanoparticles were exhaustively studied as controlled-release systems for parenteral administration of a model drug 5-aminosalicyclic acid (mesalamine) and analyzed using various release kinetic studies.     

Preparation and Evaluation of Differently Sulfonated Styrene–Divinylbenzene Cross-linked Copolymer Cationic Exchange Resins as Novel Carriers for Drug Delivery

The differently sulfonated styrene–divinylbenzene cross-linked copolymer cationic exchange resins were prepared by oil-in-water polymerization and varied degrees of sulfonation. Several characteristics of the obtained resins were evaluated, i.e., Fourier transform infrared spectra, the ion-exchange capacity, microscopic morphology, size, and swelling. The resin characteristics were altered in relation to the degree of sulfonation, proving that differently sulfonated resins could be prepared. The behavior of chlorpheniramine (CPM) loading and in vitro release in the USP simulated gastric (SGF) and intestinal fluids (SIF) of the obtained resins were also evaluated. The CPM loaded in the resinates (drug-loaded resins) increased with the increasing degree of sulfonic group and hence the drug binding site in the employed resins. The CPM release was lower from the resins with the higher degree of sulfonic group due to the increase in the diffusive path depth. The CPM release was obviously lower in SGF than SIF because CPM, a weak base drug, ionized to a greater extent in SGF and then preferred binding with rather than releasing from the resins. In conclusion, the differently sulfonated resins could be utilized as novel carriers for drug delivery.     

Preparation and pharmacodynamics of low-molecular-weight chitosan nanoparticles containing insulin

Low-molecular-weight chitosan (LMWC) was obtained by enzymatic degradation and ultrafiltration separation. LMWC nanoparticles with LMWC having 20 kDa weight average molecular weight (M_w) were then prepared by solvent evaporation method. The resultant nanoparticles were spherical with a narrow particle size distribution. LMWC nanoparticles loaded with insulin as a model drug were prepared. The average entrapment efficiency of insulin could reach up to 95.54%. The in vitro drug release profiles from the nanoparticles showed an initial burst of release in the first 2 h, followed by zero order release kinetics. In vivo pharmacodynamics of chitosan nanoparticles containing insulin showed that the nanoparticles showed some hypoglycemic activity. Compared with an insulin solution, a relative bioavailability of 0.737 was observed for four times the dosage of insulin in the chitosan nanoparticles after pulmonary administration.     

Synthesis and characterization of hydrogels based on grafted chitosan for the controlled drug release

Temperature and pH-responsive hydrogels based on chitosan grafted with poly acrylic acid (PAAc), poly hydroxy propyl methacrylate (PHPMA), poly (vinyl alcohol) (PVA) and gelatin were prepared for controlled drug delivery. These stimuli-responsive hydrogels were synthesized by gamma irradiation technique. The degree of gelation was over 90% and increased as chitosan, AAc and PVA content increased, while the degree of gelation decrease with the increase of gelatin content. The equilibrium swelling studies of hydrogels prepared in various conditions were carried out in an aqueous solution, and the pH sensitivity in the range of 2–9 was investigated. An increase of swelling degree with an increase in the pH was noticed and showed the highest value at pH 9. Also antibiotic drug Oxttetracycline was loaded into the hydrogels and the release studies were carried out at different pH and temperature. The in vitro release profiles of the drug showed that, the release of the drug increased as the time, temperature and pH increased and reached to maximum after 48 h at pH 9. The prepared hydrogels were characterized by using SEM, FTIR, and DSC.     

Immobilization of urease using glycidyl methacrylate grafted nylon-6-membranes

The graft copolymerization of glycidyl methacrylate (GMA) onto nylon-6-membrane using benzophenone (BP) as an initiator was carried out in an alcoholic aqueous solution. The acrylic double bond of GMA participated in the grafting onto the nylon-6-membrane backbone with the epoxy groups remaining unaffected. At the end of the grafting reaction, urease was immobilized onto the modified membrane. BP concentration, GMA concentration and organic solvent seperation were studied by determining the grafting percentage. The influence of urease concentration on the immobilization efficiency was also studied. With keeping other conditions constant, the optimum conditions were shown as following [BP]: 5 × 10⁻² mM; [GMA]: 10 M; [urease]: 10 mg/ml, organic solvent: methanol.     

Feruloyl esterase production by Aspergillus terreus CECT 2808 and subsequent application to enzymatic hydrolysis

Ferulic acid esterases (FAE) were produced by Aspergillus terreus CECT 2808 from vine trimming shoots (VTS) and corn cob. Later, the fungal extracts thus obtained were used to enzymatically release ferulic acid (FA) from both substrates. Our findings showed a higher FAE activity in the enzymatic extracts produced on corn cob (0.070 ± 0.004 U/mL). Nevertheless, the enzymatic extracts produced on VTS demonstrated a better performance for FA release from both corn cob (2.05 ± 0.01 mg/g) and VTS (0.19 ± 0.003 mg/g). This result was probably because of the higher xylanase/FAE ratio determined in VTS extract. Therefore, an additional assay was carried out by supplementing corn cob extract with a commercial xylanase to test the influence of FAE/xylanase ratio in FA release. The results revealed the relevance of the FAE/xylanase ratio for an optimal FA release.     

A biosensor based on gold nanoparticles,dihexadecylphosphate, and tyrosinase for the determination of catechol in natural water

In this work, a biosensor using a glassy carbon electrode modified with gold nanoparticles (AuNPs) and tyrosinase (Tyr) within a dihexadecylphosphate film is proposed. Cystamine and glutaraldehyde crosslinking agents were used as a support for Tyr immobilization. The proposed biosensor was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and cyclic voltammetry in the presence of catechol. The determination of catechol was carried out by amperometry and presented a linear concentration range from 2.5 × 10⁻⁶ to 9.5 × 10⁻⁵ mol L⁻¹ with a detection limit of 1.7 × 10⁻⁷ mol L⁻¹. The developed biosensor showed good repeatability and stability. Moreover, this novel amperometric method was successfully applied in the determination of catechol in natural water samples. The results were in agreement with a 95% confidence level for those obtained using the official spectrophotometric method.     

Preparation of electrospun alginate fibers with chitosan sheath

In this study, alginate (AL) fibers were electrospun and coagulated with chitosan (ChS) and ethanol using a single spinneret. These fibers exhibited a core–sheath structure that was revealed using a confocal laser scanning microscope (CLSM) and fluorescence-labeled polymers. The resulting fibers were examined using a field emission scanning electron microscope (FESEM) for the fiber size and morphology. The average diameter of the fibers ranged from 600 to 900 nm depending on the electrospinning parameters. To mimic the stability of alginate fibers in physiological fluids, the release of alginate from these fibers in normal saline was also tested. The results demonstrated that the core–sheath structure of alginate fiber can greatly reduce the degradation by 40% for 3 d in physiological environment.     

Chitosan cross-linked with poly(ethylene glycol)dialdehyde via reductive amination as effective controlled release carriers for oral protein drug delivery

The covalently cross-linked chitosan-poly(ethylene glycol)₁₅₄₀ derivatives have been developed as a controlled release system with potential for the delivery of protein drug. The swelling characteristics of the hydrogels based on these derivatives as the function of different PEG content and the release profiles of a model protein (bovine serum albumin, BSA) from the hydrogels were evaluated in simulated gastric fluid with or without enzyme in order to simulate the gastrointestinal tract conditions. The derivatives cross-linked with difunctional PEG₁₅₄₀-dialdehyde via reductive amination can swell in alkaline pH and remain insoluble in acidic medium. The cumulative release amount of BSA was relatively low in the initial 2 h and increased significantly at pH 7.4 with intestinal lysozyme for additional 12 h. The results proved that the release-and-hold behavior of the cross-linked CS–PEG₁₅₄₀H-CS hydrogel provided a swell and intestinal enzyme controlled release carrier system, which is suitable for oral protein drug delivery.     

Design,synthesis and ex-vivo release studies of colon-specific polyphosphazene–anticancer drug conjugates

Colon-specific azo based polyphosphazene–anticancer drug conjugates (11–18) have been synthesized and evaluated by ex-vivo release studies. The prepared polyphosphazene drug conjugates (11–18) are stable in acidic (pH = 1.2) buffer which showed that these polymer drug conjugates are protected from acidic environment which is the primary requirement of colon specific targeted drug delivery. The ex-vivo release profiles of polyphosphazene drug conjugates (11–18) have been performed in the presence as well as in the absence of rat cecal content. The results showed that more than 89% of parent drugs (methotrexate and gemcitabine) are released from polymeric backbone of polyphosphazene drug conjugates (14 and 18) having n-butanol (lipophilic moiety). The in-vitro cytotoxicity assay has also been performed which clearly indicated that these polymeric drug conjugates are active against human colorectal cancer cell lines (HT-29 and COLO 320 DM). The drug release kinetic study demonstrated that Higuchi’s equation is found to be best fitted equation which showed that release of drug from polymeric backbone as square root of time dependent process based on non-fickian diffusion. Therefore, the synthesized polyphosphazene azo based drug conjugates of methotrexate and gemcitabine are the potential candidates for colon targeted drug delivery system with minimal undesirable side effects.     

Polydimethylsiloxane modified chitosan. Part III: Preparation and characterization of hybrid membranes

The paper deals with the synthesis of organic–inorganic hybrid membranes, Hy, obtained by simultaneous grafting and crosslinking of chitosan with epoxy-terminated polydimethylsiloxane and γ-glycidoxypropyltrimethoxysilane. Porous membranes, HyP, were also obtained by acid decomposition, at different temperatures (25 and 50 °C), of calcium carbonate porogenic agent trapped inside the material. As proved by electron and atomic force microscopy, the non-porous membrane is a phase segregated material with spherical domains (10–40 μm) of silica core covered by hydrophobic siloxane in a hydrophilic chitosan matrix. The porous membranes showed different morphologies with irregular circular pores of 10–30 μm diameters for the membranes obtained at lower temperature, while the membranes prepared at 50 °C tend to adopt a plan-parallel porosity. The water contact angles of hybrid membranes (78°) and pure chitosan membranes (72°) indicated a lower hydrophilic character of modified chitosan. As a result of the crosslinking and of increased hydrophobicity, the hybrid membranes were characterized by a smaller water swelling degree (about 30%) as compared to pure chitosan membrane (700%). However, the presence of the pores in HyP membranes determined an increase of the water adsorption (maximum swelling degree, about 100%). The hybrid membranes possess a slightly higher thermal stability as compared to chitosan (first initial decomposition temperature, 147 and 175 °C for chitosan and hybrid membranes, respectively), but a lower one as compared to pure polydimethylsiloxane. The high storage modulus of chitosan (about 5.1 × 10⁹ Pa at 20 °C) is decreased by about one order of magnitude by the introduction of the highly flexible polysiloxane and the hybrid membranes are more flexible.     

Immobilization of cellulase on polyamidoamine dendrimer-grafted silica

Polyamidoamine dendrimer (PAMAM) is one of a number of dendritic polymers with precise molecular structure, highly geometric symmetry, and a large number of terminal groups, and is suitable to carry biomolecules due to its affinity and biocompatibility. In this study, PAMAM was grafted onto the surface of silica by microwave irradiation. A novel media was developed through immobilizing cellulase onto the prepared PAMAM-grafted silica by adsorption and crosslinking methods and applied in hydrolysis of carboxymethyl cellulose. The results demonstrate that the enzyme binding capacity and enzymolysis efficiency increased with generations of PAMAM. The properties of the immobilized cellulase-PAMAM-grafted silica were investigated, which possessed high enzymatic activity and exhibited better stability with respect to pH, temperature compared with free enzyme. The optimal immobilization conditions for adsorption and crosslinking method were respectively obtained at 5 and 4 mg ml⁻¹ cellulase for 2 h of immobilization. A high enzymolysis efficiency was achieved by employing pH 4.8 and 5.8 substrate solution at 60 °C for adsorbed and crosslinked cellulase, respectively. After repeated three run cycles, the retained activities were found to be 75% and 82%. The results indicate that the PAMAM has a good performance as a carrier, and can be potentially adapted to support other biomacromolecules.     

The Constant score and the assessment of scapula dyskinesis: Proposal and assessment of an integrated outcome measure

The Constant–Murley score (CMS) is a popular measure of shoulder function. However, its ability to monitor the evolution of patients during rehabilitation after rotator-cuff repair is controversial. Moreover, CMS does not account for possible alterations in the scapulo-humeral coordination (SHC, scapula dyskinesis), which are apparent in variety of shoulder pathologies. To address these issues, a new formulation of CMS was firstly proposed, which rates the “affected-to-controlateral side difference in SHC” of a patient with respect to reference values of asymptomatic controls (Scapula-Weighted CMS). Then, 32 patients (53 ± 9 year-old) were evaluated with CMS and SW-CMS at 45, 70, 90-day and >6-month after rotator-cuff repair, to test three hypotheses: (1) CMS and SW-CMS are largely responsive to change; (2) accounting (SW-CMS) or not (CMS) for scapula dyskinesis leads to statistically different scores and SW-CMS cannot be predicted from CMS without clinically relevant differences; (3) 90% of patients recover a side-to-side SHC similar to asymptomatic controls at 90 days. Results supported hypotheses 1 and 2. On the contrary (hypothesis 3), only 10% of patients recovered for SHC alterations at 90 days, and 50% at follow-up. These findings support the use of SW-CMS and the importance of treating scapula dyskinesis after rotator-cuff repair.     

Synthesis and characterization of methacrylic derivatives of 5-amino salicylic acid with pH-sensitive swelling properties

The purpose of this study is to develop novel colon-specific drug delivery systems with pH-sensitive swelling and drug release properties. Methacrylic-type polymeric prodrugs with different content levels of 5-amino salicylic acid (5-ASA) were synthesized by free radical copolymerization of metacrylic acid (MAA), polyethylene glycol monomethacrylate (PEGMA), and a methacrylic derivative of 5-ASA (methacryloyloxyethyl 5-amino salicylate [MOES]). The copolymers were characterized, and the drug content of the copolymers was determined. The effect of copolymer composition on the swelling behavior and hydrolytic degradation was studied in simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.2). The swelling and hydrolytic behavior of the copolymers was dependent on the content of MAA groups and caused a decrease in gel swelling in SGF or an increase in gel swelling in SIF. Drug release studies showed that increasing content of MAA in the copolymer enhances the hydrolysis in SIF but has no effect in SGF. The results suggest that hydrogen-bonded complexes are formed between MAA and PEG pendant groups and that these pH-sensitive systems could be useful for preparation of a controlled-release formulation of 5-ASA.     

Development of doxorubicin loading platform based albumin-sporopollenin as drug carrier

Albumin is thought as an drug carrier for doxorubicin (DOX). The binding of doxorubicin to albumin was studied on the surface of sporopolleninin (SP) to produce a new drug system based natural materials. Human serum albumin (HSA) was immobilized on SPIONs in 20 mM Tris buffer, 7.4 of pH. Data showed that binding amount of HSA has been found to be as 285.53 µg to the 25 mg of Sporopolleninin which also bounded 319.76 µM of DOX. Binding of protein and drug to Sp were clarified by SEM, EDX and FT-IR analysis.     

NMR spectroscopy and imaging studies of pharmaceutical tablets made of starch

Modified polysaccharides such as high amylose starch are used as excipient in controlled drug release technology. Crosslinked high amylose starch is a hydrophilic matrix used for the sustained release of drugs. Tablets using modified hybrid starch as excipient display zero-order release over 2–24 h. A release over 3–4 weeks was observed when the modified starch is used as an implant. The use of starch in controlled release system is appealing because it could be easily metabolized in the human body. We review here the use of NMR imaging and solid state ¹³C spectroscopy in the study of the various factors influencing drug release in such systems.     

Chitosan microcapsules loaded with either miconazole nitrate or clotrimazole,prepared via emulsion technique

In this paper, a simple and versatile coacervation technique has been developed by using an ultrasound-assisted oil/water emulsion method for the preparation of antifungal agent-loaded microcapsules. Two types of chitosan microcapsules are successfully prepared. The mean particle size of the chitosan/miconazole nitrate microcapsules is 2.6 μm and that of the chitosan/clotrimazole microcapsules is 4.1 μm. The encapsulation efficiency of the chitosan/miconazole nitrate microcapsules (77.58–96.81%) is relatively higher than that of the chitosan/clotrimazole microcapsules (56.66–93.82%). The in vitro drug release performance of the microcapsules shows that the chitosan/miconazole nitrate microcapsules release about 49.5% of the drug while chitosan/clotrimazole microcapsules release more than 66.1% of the drug after 12 h under a pressure of 5 kg at pH 5.5, which is similar to the pH of human skin. The prepared drug-loaded microcapsules could be applied onto bandages or socks, and will continuously release antifungal drugs in a controlled manner under pressure.     

Bioremediation of phenol-contaminated water and soil using magnetic polymer beads

In order to easily separate pollutant-absorbing polymer beads from contaminated soil or water, novel polymer beads containing magnetic particles were developed. The polymer beads containing 4.67% (w/w) magnetic particles exhibited an almost identical partitioning coefficient for phenol compared to that of the pure polymer. A 1.5 L phenol solution of 2000 mg/L added to a bioreactor was reduced to 481 mg/L phenol within 3 h by adding 100 g of these magnetic beads, and the phenol was completely degraded by microorganisms in 16 h. The magnetized beads were then readily removed from the bioreactor by a magnet with 10,000 G, and subsequently detached for re-use. 500 g of soil contaminated with 4 mg-phenol/g-soil was also contacted with 100 g beads, and greater than 97% removal of phenol from the soil was achieved within 1 day. The phenol-absorbing beads were easily separated from the soil by the magnet and transferred into a fermentor. The phenol was released from the beads and was degraded by the microorganism in 10 h. Modifying polymers to possess magnetic properties has greatly improved the ease of handling of these sequestering materials when decontaminating soil and water sources, in conjunction with contaminant release in partitioning bioreactors.