Double network structure via ionic bond and covalent bond of carboxymethyl chitosan and poly(ethylene glycol): Factors affecting hydrogel formation.

The factors were studied that affect the formation of DN hydrogel, which was prepared using a water-based, environmental-friendly system. The DN hydrogel was designed and prepared based on a cross-linked, polysaccharide-based, polymer carboxymethyl chitosan (CMCS) via an ionic crosslinking reaction for the first network structure. UV irradiation created a radical crosslinking reaction of poly(ethylene glycol) from a double bond at the chain end for the second network structure. It was found that the optimum hydrogel was produced using 9.5 %v/v of 1000PEGGMA, CMCS 5%w/v, and CaCl2 3%w/v. The results showed the highest percentage of the gel fraction was 87.84 % and the hydrogel was stable based on its rheological properties. Factors affecting the hydrogel formation were the concentration and molecular weight of PEGGMA and the concentrations of CMCS and calcium chloride (CaCl2). The DN hydrogel had bioactivity due to its octacalcium phosphate (OCP) hydroxyapatite crystal form. In addition, the composite DN scaffold with a conductive polymer of chitosan-grafted-polyaniline (CS-g-PANI) had conduction of 2.33 × 10-5 S/cm when the concentration of CS-g-PANI was 3 mg/ml, confirming the semi-conductive nature of the material. All the results indicated that DN hydrogel could be a candidate to apply in tissue-engineering applications.

Bioactivity of star-shaped polycaprolactone/chitosan composite hydrogels for biomaterials.

Recently, our group reported the synthesis and fabrication of composite hydrogels of chitosan (CS) and star-shaped polycaprolactone (stPCL). The co-crosslink of modified stPCL with carboxyl at the end chain (stPCL-COOH) provided good mechanical properties and stability to the composite hydrogels. This research presents the bioactivities of composite hydrogels showing a potential candidate to develop biomaterials such as wound dressing and bone tissue engineering. The bioactivities were the antibacterial activity, cell viability, skin irritation, decomposability, and ability to attach ions for apatite nucleation. The results showed that all the composite hydrogels were completely decomposed within 2 days. The composite hydrogels had better antibacterial activity and higher efficiency to Gram-negative (Escherichia coli) than to Gram-positive (Staphylococcus epidermidis) bacteria. The composite hydrogels were studied for cell viability based on MTT assay and skin irritation on rabbit skin. The results indicated high cell survival more than 80% and no skin irritation. In addition, the results showed that calcium and phosphorous were preferentially attached to the composite hydrogel surface to grow apatite crystal (Ca/P ratio 1.86) compared to attaching to the chitosan hydrogel (Ca/P ratio 1.48) in 21 days of testing.

Camptothecin-incorporating N-phthaloylchitosan-g-mPEG self-assembly micellar system: effect of degree of deacetylation.

Amphiphilic grafted copolymers, N-phthaloylchitosan-grafted poly (ethylene glycol) methyl ether (PLC-g-mPEG), were synthesized from chitosan with different degree of deacetylation (DD=80%, 85%, 90% and 95%). Due to their amphiphilic characteristic, these copolymers could form micelle-like nanoparticles. The critical micelle concentration (CMC) of these nanoparticles with different DD in water was similar (28microg/ml). Under transmission electron microscope (TEM), the nanoparticles exhibited a regular spherical shape with core-shell structure. The particle sizes determined by dynamic light scattering were in the range of 100-250nm, and increased as the %DD of chitosan increased. The cytotoxicity of phthaloylchitosans (PLC) and PLC-g-mPEG in Hela cells line were evaluated. The results showed that cytotoxicity of PLC and PLC-g-mPEG increased with increasing %DD of chitosan. The cytotoxicity of PLC-g-mPEG was significantly lower than that of PLC. Camptothecin as a model drug was loaded into the inner core of the micelles by dialysis method. It was found that %DD of chitosan, corresponding to the N-phthaloyl groups in the inner core of the nanoparticle obtained, was a key factor in controlling %yield, stability of the drug-loaded micelles, and drug release behavior. As the %DD increased, the CPT-loaded micelles stability increased. Release of CPT from the micelles was dependent on the %DD and a sustained release was obtained in high %DD.

N-phthaloylchitosan-g-mPEG design for all-trans retinoic acid-loaded polymeric micelles.

The amphiphilic grafted copolymer N-phthaloylchitosan-grafted poly(ethylene glycol) methyl ether (PLC-g-mPEG) was synthesized using chitosan with four different degrees of deacetylations (DD) (80, 85, 90 and 95%). All-trans retinoic acid (ATRA) was incorporated into PLC-g-mPEG by dialysis method in an attempt to optimize carriers for ATRA delivery. Morphological investigation by transmission electron microscopy (TEM) showed that the particles had round and uniform shapes. The particle sizes of ATRA incorporated into micelles were about 80-160 nm depending on the initial drug-loaded and %DD of chitosan. Physicochemical properties of ATRA-loaded polymeric micelles were also investigated. It was found that %DD of chitosan, which corresponded to the N-phthaloyl groups in the inner core of the micelles, was a key factor in controlling the incorporation efficiency, stability of the drug-loaded micelles and drug release behavior. As the %DD increased, the incorporation efficiency and ATRA-loaded micelles stability increased. The sustained release profiles were also obtained at high %DD (90 and 95%). When compared to the unprotected ATRA, ATRA loaded in PLC-g-mPEG micelles was efficiently protected from photodegradation. This result suggested that loading of ATRA in micelles improved the chemical stability of ATRA.

Incorporation of camptothecin into N-phthaloyl chitosan-g-mPEG self-assembly micellar system.

The capability of N-phthaloylchitosan-grafted poly (ethylene glycol) methyl ether (mPEG)(PLC-g-mPEG) to enhance the aqueous solubility and stability of the lactone form of camptothecin (CPT) was investigated. PLC-g-mPEG formed a core-shell micellar structure after dialysis of the polymer solutions in dimethyl sulfoxide (DMSO) or dimethylformamide (DMF) against water, with a critical micelle concentration (CMC) of 28 microg/ml. CPT was loaded into the inner core of the micelles by dialysis method. The results showed an increase in the CPT-loading amount with an increasing concentration of CPT. The stability of drug-loaded micelles was studied by gel-permeation chromatography (GPC), and their in vitro release behaviors were analyzed. Release of CPT from the micelles was sustained. When compared to the unprotected CPT, CPT-loaded PLC-g-mPEG micelles were able to prevent the hydrolysis of the lactone group of the drug. The kinetics of the CPT hydrolysis in human serum albumin (HSA) and fetal bovine serum (FBS) were pseudo-first order. The hydrolysis rate constants for CPT and CPT-loaded PLC-g-mPEG micelles in phosphate-buffered saline (PBS) pH 7.4, were 7.4 x 10(-3) min(-1) and 9.1 x 10(-3) h(-1), parallel to an increase in half-life of CPT from 94 min to 76.15 h, respectively.