In this investigation, superporous hydrogels containing poly (acrylic acid-co-acrylamide)/O-carboxymethyl chitosan (O-CMC) fullinterpenetrating polymer networks (SPH-IPNs) were evaluated for their potentials in effective insulin absorption via the oral route. Insulin release from the SPH-IPNs exhibited sensitivity towards pH and ionic strength. After drug loading and release, the circular dichroism (CD) spectra revealed that conformation of insulin had no significant alteration and bioactivity of insulin was well preserved according to hypoglycaemic effect in mice. Through their abilities to bind Ca2+ and to entrap the enzymes, SPH-IPNs could partly inactivate trypsin and-chymotrypsin, and SPH-IPN with higher O-CMC/monomer ratio appeared more potent. Swollen SPH-IPNs could attach mechanically and muco-adhere to the intestinal wall, thus achieving improved retentive properties compared to commonly used muco-adhesive excipient Carbopol? 934. Transport of insulin across rat intestine and colon ex vivo was enhanced around two- to three-fold after application of the SPH-IPN. Insulin-loaded SPH-IPN showed significant hypoglycaemic effects following oral administration to healthy rats, achieving a 4.1% pharmacological availability compared to subcutaneous insulin injection. These pronounced properties demonstrated that the SPH-IPN would be a promising peroral carrier for insulin and other peptide drugs.

A new type of nanocapsules with an oil core, coated by poly(ethylene glycol) (PEG) was designed. The loading efficiency and the biocompatibility of the polymeric nanocapsules were evaluated when it was used as a carrier for hydrophobic agent paclitaxel. The nanocapsules were synthesized through miniemulsion polymerization of butylcyanoacrylate (BCA) with PEG as initiator. The particle size and zeta potential of nanocapsules were influenced by the PEG content in the polymerization system. Fourier transform infrared (FTIR) spectra and 1H NMR demonstrated the chemical coupling between PEG and poly(butylcyanoacrylate) (PBCA). Thermal characteristics of the copolymer were investigated by differential scanning calorimetry (DSC). The encapsulation efficiency increased concurrently with the increase of the PEG content in the system. The hemolytic assay and the cytotoxicity measurement showed that the PEG coating could significantly reduce the hemolytic potential and cytotoxicity of the nanocapsules. The results showed that the PEG-PBCA nanocapsules could be an effective carrier for hydrophobic agents.

A smart polymeric composite carrier consisting of carboxylated chitosan grafted nanoparticles (CCGN) and bilaminated films with one alginate-Ca2+ mucoadhesive layer and one hydrophobic backing layer was developed as a novel carrier for peptide. Calcein, hydrophilic and hydrolytic degradative, was entrapped into CCGN as a model peptide and its release behavior was investigated. Morphology study showed a uniform distribution of CCGN in the homogeneous and porous hydrogel. CCGN was characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), particle size measurement, and f potential measurement. The composite carrier was characterized by differential scanning calorimetry (DSC), scanning electron microscope (SEM) and fluorescence microscopy. The carrier exhibited high mucoadhesive force and pH-sensitivity, in that release of the nanoparticles and the model peptide calcein were both restricted in acidic environment while a fast and complete release was achieved in neutral medium. Therefore, this novel carrier would be a promising candidate for hydrophilic peptide drugs via oral administration.

Superporous hydrogels containing poly(acrylic acid-co-acrylamide)/O-carboxymethyl chitosan interpenetrating polymer networks (SPH-IPNs) were prepared by cross-linking O-carboxymethyl chitosan (O-CMC) with glutaraldehyde (GA) after superporous hydrogel (SPH) was synthesized. The structures of the SPH-IPNs were characterized with FT-IR, 13C-NMR and DSC. SEM, CLSM and light images revealed that the SPH-IPNs possessed both the IPN network and large numbers of pores and the cross-linked O-CMC molecules were located on the peripheries of these pores. The swelling behavior of SPH-IPNs was dependent on the O-CMC content, GA amount and cross-linking time. Due to the cross-linked O-CMC network, in vitro muco-adhesive force and mechanical properties, including compression and tensile modulus, of the SPH-IPN were greatly improved when compared with the CSPH. An enhanced loading capacity for insulin could be obtained by the SPH-IPNs as compared to non-porous hydrogel and CSPH, and more than 90% of the insulin was released within 1h. With the improved mechanical properties, in vitro muco-adhesive force and loading capacities, the SPH-IPN may be used as a potential muco-adhesive system for peroral delivery of peptide and protein drugs.

Chitosan-N-trimethylaminoethylmethacrylate chloride-PEG (CS-TM-PEG) copolymers were synthesized in order to improve the solubility of chitosan in physiological environment, and enhance the biocompatibility of quaternized chitosan. The result of 1H NMR confirmed that PEG had been combined with amino groups of quaternized chitosan. The profile of hemolysis assay showed that Chitosan-N-trimethylaminoethylmethacrylate chloride (CS-TM) copolymer exhibited hemolytic activity from 10.31% to 13.58%, while CS-TM-PEG copolymer had hemolytic activity from 4.76% to 7.05% at copolymer concentrations from 250 to 2000 lg/ml. Through PEG modification, the hemolytic activity could be reduced to a half. CS-TM-PEG copolymer-insulin nanoparticles were prepared based on ionic gelation process of positively charged copolymers and negatively charged insulin. The nanoparticles were characterized in terms of particle size, TEM, association efficiency and in vitro release. These nanoparticles were 200-400 nm in size and insulin association efficiency of optimal formulations was found up to 90%. In vitro release showed that the nanoparticles provided an initial burst release followed by a sustained release with the sensitivity of ionic strength and pH values.