Preparation and characteristics of linoleic acid-grafted chitosan oligosaccharide micelles as a carrier for doxorubicin

The linoleic acid (LA)-grafted chitosan oligosaccharide (CSO) (CSO-LA) was synthesized in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), and the effects of molecular weight of CSO and the charged amount of LA on the physicochemical properties of CSO-LA were investigated, such as CMC, graft ratio, size, zeta potential. The results showed that these chitosan derivatives were able to self-assemble and form spherical shape polymeric micelles with the size range of 150.7–213.9 nm and the zeta potential range of 57.9–79.9 mV, depending on molecular weight of CSO and the charged amount of LA. Using doxorubicin (DOX) as a model drug, the DOX-loaded CSO-LA micelles were prepared by dialysis method. The drug encapsulation efficiencies (EE) of DOX-loaded CSO-LA micelles were as high as about 75%. The sizes of DOX-loaded CSO-LA micelles with 20% charged DOX (relating the mass of CSO-LA) were near 200 nm, and the drug loading (DL) capacity could reach up to 15%. The in vitro release studies indicated that the drug release from the DOX-loaded CSO-LA micelles was reduced with increasing the graft ratio of CSO-LA, due to the enhanced hydrophobic interaction between hydrophobic drug and hydrophobic segments of CSO-LA. Moreover, the drug release rate from CSO-LA micelles was faster with the drug loading. These data suggested the possible utilization of the amphiphilic micellar chitosan derivatives as carriers for hydrophobic drugs for improving their delivery and release properties.     

Preparation and characterization of stearic acid nanostructured lipid carriers by solvent diffusion method in an aqueous system

Nanostuctured lipid carriers (NLC) based on mixture of solid lipids with spatially incompatible liquid lipids are a new type of lipid nanoparticles, which offer the advantage of improved drug loading capacity and release properties. In present study, stearic acid (SA) nanostuctured lipid carriers with various oleic acid (OA) content were successfully prepared by solvent diffusion method in an aqueous system. The size and surface morphology of nanoparticles were significantly influenced by OA content. As OA content increased up to 30 wt%, the obtained particles showed pronounced smaller size and more regular morphology in spherical shape with smooth surface. Compared with solid lipid nanoparticles (SLN), NLC exhibited improved drug loading capacity, and the drug loading capacity increased with increasing OA content. These results were explained by differential scanning calorimetry (DSC) investigations. The addition of OA to nanoparticles formulation resulted in massive crystal order disturbance and less ordered matrix of NLC, and hence, increased the drug loading capacity. The drug in vitro release behavior from NLC displayed biphasic drug release pattern with burst release at the initial stage and prolonged release afterwards, and the successful control of release rate at the initial stage can be achieved by controlling OA content.     

Preparation and characterization of N-succinyl-N'-octyl chitosan micelles as doxorubicin carriers for effective anti-tumor activity

N-Succinyl-N′-octyl chitosan (SOC) was prepared and characterized by elemental analysis, FTIR, ¹H NMR, WAXD and TG. An anticancer drug, doxorubicin (DOX), was incorporated into polymeric micelles forming by SOC in aqueous solutions. Critical micelle concentrations (CMC) of SOC were determined by fluorescence spectroscopy. The DOX-loaded SOC micelles were characterized by measurement of size and drug loading. The loading content of DOX increased with increasing drug-to-carrier ratio, and the more amount of the octyl chain, the higher the drug loading content. The average size, which was affected by the amount of octyl chain and drug loading content, was in the range of 100–200 nm. The polymeric micelles containing doxorubicin in the core region exhibited a sustained release and more cytotoxic activity against HepG2, A549, BGC and K562 than doxorubicin alone, this can be attributed to an endocytosis mechanism rather than passive diffusion.     

Radiation synthesis of chitosan beads grafted with acrylic acid for metal ions sorption

Radiation-induced grafting of acrylic acid onto chitosan beads was performed in solution at a dose rate of 20.6 Gy/min of cobalt-60 gamma rays. The effect of absorbed dose on grafting yield was investigated. The characterization of the grafted material was performed by FTIR spectroscopy and the swelling measurements at different pHs. The grafting yield increased with the increase in dose, it reached 80% at 40 kGy irradiation dose.The removal of Pb and Cd ions from aqueous solutions was investigated with both ungrafted and grafted chitosan beads. The sorption behavior of the sorbents was examined through pH, kinetics and equilibrium measurements. Grafted chitosan beads presented higher sorption capacity for both metal ions than unmodified chitosan beads.     

Biodegradable hyaluronic acid/n-carboxyethyl chitosan/protein ternary complexes as implantable carriers for controlled protein release

An ampholytic N-carboxyethyl chitosan (CEC), with various isoelectric points (IPs), was synthesized by grafting acrylic acid on chitosan utilizing Michael's reaction. Compared to native chitosan, CEC has enhanced water solubility and dramatically accelerated enzymatic degradation; the rate of degradation is proportional to the degree of substitution (DS). The results from turbidimetric titration and fluorescence studies revealed that CEC formed complexes with either hyaluronic acid (HA) or bovine serum albumin (BSA) within a certain pH range. The HA/CEC/BSA ternary complexes could be prepared by colloid titration with quantitative yield and BSA entrapment. The rate of BSA release from the complexes was affected by pH, ionic strength, DS of CEC, and the molecular weight (MW) of HA. The endurance of BSA release from the complexes could be extended up to 20 d by formulating them with high-MW HA and CEC with low DS.BSA release profiles from HA/CEC-2/BSA complexes.     

Carboxymethylcellulose-coated magnesium-layered hydroxide nanocomposite for controlled release of 3-(4-methoxyphenyl)propionic acid

Carboxymethylcellulose (CMC) acts as a coating material for a magnesium-layered hydroxide-3-(4-methoxyphenyl)propionate (MLH-MPP) nanocomposite via spontaneous self-assembly. The resulting product is called a magnesium-layered hydroxide-3-(4-methoxyphenyl)propionate/carboxymethylcellulose (MLH-MPP/CMC) nanocomposite. The XRD pattern of the MLH-MPP/CMC nanocomposite showed that MPP was maintained in the interlayers of the MLH, thus confirming that CMC is only deposited on the surface of the MLH-MPP nanocomposite. These findings were also supported by FTIR spectra, SEM and TEM. TGA data showed that the thermal stability of the intercalated MPP was significantly enhanced compared to pure MPP and uncoated nanocomposite. The release of MPP from the interlayers of MLH-MPP/CMC nanocomposite showed slower release than did uncoated nanocomposite and followed pseudo–second-order kinetics. Since the herbicide, MPP was released from the synthesised nanocomposite in a sustained manner, thus, it has excellent potential to be used as a controlled-release herbicide formulation.     

Preparation and characterization of biodegradable gelatin-PAAm-based IPN hydrogels for controlled release of maleic acid to improve the solubility of phosphate fertilizers

In this study, interpenetrating polymer network (IPN) hydrogel systems including maleic acid (MA) were constituted to improve the solubility of phosphate fertilizers. A series of full and semi-IPN hydrogels were prepared from various gelatin/polyacrylamide mixtures by using two different cross-linkers. The effects of polymer composition on the morphological structures and swelling behaviors of the hydrogels were investigated. The swelling values of all hydrogels were found to be in between 435% and 830%. MA release from load0ed hydrogels was followed and it was determined that MA-loaded hydrogels efficiently decreased pH and improved the solubility of Ca₃(PO₄)₂ in releasing medium.     

Synthesis of cross-linked carboxymethyl cellulose and poly (2-acrylamido-2-methylpropane sulfonic acid) hydrogel for sustained drug release optimized by Box-Behnken Design

This research aims to fabricate and characterize chemically crosslinked CMC/PVP-co-poly (AMPS) based hydrogel for the sustained release of model drug metoprolol tartrate through the free radical polymerization technique. Box-Behnken Design was used to optimize CMC/PVP-co-poly (AMPS) hydrogel by varying the content of reactants such as; polymers (CMC and PVP), monomer (AMPS), and crosslinker (EGDMA). Carboxymethyl cellulose (CMC) was crosslinked chemically with AMPS with a constant ratio of PVP by the ethylene glycol dimethacrylate as the crosslinker in the presence of sodium hydrogen sulfite (SHS)/ammonium peroxodisulfate (APS) as initiators. After developing CMC-based hydrogels using different polymers, monomer, and crosslinker concentrations, this study encompassed dynamic swelling, sol–gel fraction, drug release and chemical characterizations such as FTIR, XRD, TGA, DSC, and SEM. In vitro drug release and swelling were performed at 1.2 and 6.8 pH to determine the sustained release pattern and pH-responsive behavior. These parameters depended on the crosslinker, polymer, and monomer ratios used in the formulation development. XRD, SEM, and FTIR showed the successful grafting of constituents resulting in the formation of a stable hydrogel. DSC and TGA confirmed the thermodynamic stability of the hydrogel. Hydrogel swelling was increased with an increase in the ratio of monomer; however, an increase in the ratio of polymer and crosslinker decreased the hydrogel swelling. In vitro gel fraction and drug release also depended on polymer, monomer, and crosslinker ratios. The fabricated CMC/PVP-co-poly (AMPS) hydrogels constituted a potential system for sustained drug delivery.     

In vitro degradation and release behavior of porous poly(lactic acid) scaffolds containing chitosan microspheres as a carrier for BMP-2-derived synthetic peptide

To develop a novel tissue engineering scaffold with the capability of controlled releasing BMP-2-derived synthetic peptide, porous poly(lactic acid)/chitosan microspheres (PLA/CMs) composites containing different quantities of chitosan microspheres were prepared by a thermally induced phase separation method. FTIR analysis revealed that there were strong hydrogen bond interactions between the PLA and chitosan component. Introduction of less than 30% CMs (on PLA weight basis) did not remarkably affect the morphology and porosity of the PLA/CMs scaffolds. The compressive strength of the composite scaffolds increased from 0.48 to 0.66 MPa, while the compressive modulus increased from 7.29 to 8.23 MPa as the microspheres' contents increased from 0% to 50%. In vitro degradability investigation indicated that the dissolution of chitosan component was preferential than PLA matrix and the inclusion of CMs could neutralize the acidity of PLA degradation products. Compared with the rapid release from CMs, the synthetic peptide was released from PLA/CMs scaffolds in a temporally controlled manner, mainly depending on the degradation of PLA matrix. The promising microspheres based scaffold release system can be used to deliver bioactive factors for a variety of non-loaded bone regeneration and tissue engineering application.     

Development of biodegradable co-poly( -lactic/glycolic acid) microspheres for the controlled release of 5-FU by the spray drying method

The water-soluble anti-cancer drug, 5-fluorouracil (5-fluoro-2,4-pyrimidinedione) (5-FU) is encapsulated into biodegradable co-poly ( -lactic/glycolic acid) (PLGA) using the spray drying method for the development of long-lasting controlled release systems. In this study, the effects of both polymeric composition and technological parameters on release profiles of 5-FU were investigated. The degradation of various microspheres was also investigated. The mixture of dichloromethane/chloroform/methanol (1:1:2 v/v) instead of dichloromethane/chloroform (1:1 v/v) resulted in the modification of morphology, while the physical structure of the microsphere varied from a porous PLGA microsphere to a dense PLGA microsphere. The results show that the average diameter was 2 μm and the anti-cancer drug loading of microspheres approached approximately 8% (w/w). In addition, the lactide/glycolide ratio of the polymer is an important parameter for controlling the release profile of the entrapped anticancer drug. Our results indicate that the mixture solvent using the spray drying method was more efficient than emulsification solvent diffusion.