Novel spray dried pH-sensitive polyacrylamide-grafted-carboxymethylcellulose sodium copolymer microspheres for colon targeted delivery of an anti-cancer drug

Abstract

Unique pH-sensitive spray dried microspheres were formulated employing hydrolyzed polyacrylamide-g-carboxymethylcellulose sodium (PAAm-g-NaCMC) co-polymer for colon targeted delivery of an anticancer drug, capecitabine. Synthesis of PAAm-g-NaCMC was carried out through free radical polymerization, which was supported with an inert atmosphere and then the alkaline hydrolysis was performed and subjected for characterization including FTIR spectroscopic analysis, H NMR spectroscopic analysis, elemental analysis, viscosity measurement, neutralization equivalent and thermo-gravimetric investigation. The swelling data suggested that the PAAm-g-NaCMC possesses significant pH-sensitive property. The microspheres were in the range of 1.00 to 7.34 μ and the drug entrapment efficiency ranged between 70.98 and 94.41%. In vitro drug release suggested the failure of microspheres formulated using native NaCMC which failed to impede drug release in stomach and small intestine, while those prepared with pH-sensitive PAAm-g-NaCMC copolymer and cross-linked with glutaraldehyde are suitable for colon targeting because they retarded release of drug in physiologic atmosphere of stomach and small intestine. Only 12.97% of drug was released from CMC10 formulation by the end of 5th h and rest of drug has been targeted to colonic region. A sudden increase in release of drug was observed in rat caecal contents media because of colonic bacterial action on PAAm-g-NaCMC copolymer.

Solid Dispersions of Gefitinib Prepared by Spray Drying with Improved Mucoadhesive and Drug Dissolution Properties

“…Such a strategy would prevent premature and undesirable rupture of the polymeric membrane in upper parts of the gastrointestinal tract such as the stomach and intestine. Spray drying is a successful and widely used technique to prepare coated particulate drug delivery system for different purposes including colon-targeted drug delivery (10).…”

Cellulose-Based Irreversible Hydrogels Used for CO2 Sequestration

“…Finally, the grafting efficiency of DMAPMAm onto NaCMC, which was defined as the ratio of actual molar number of DMAPMAm in the copolymer to the feed content, 36 was calculated from the integral of characteristic groups in 1 H NMR spectra. As depicted in Figure 2a, one can find that the characteristic peaks of NaCMC are detected at 3.2−4.6 ppm; among them, the peaks between 3.2 and 4.1 ppm can be assigned to the protons on the sugar ring, while the characteristic peaks at 4.54 and 4.26 ppm belong to the protons of substitution groups, carboxymethyl, 29,37 suggesting that the carboxymethyl groups were successfully grafted onto cellulose chains. As for the PDMAPMAm sample, the characteristic proton peaks (Figure 2b) of the polymer are evidenced at 0.94−1.09 ppm (b), 1.67 ppm (d), 2.11 ppm (a), 2.23 ppm (f), 2.38 ppm (e), and 3.11 ppm (c), respectively, which are in line with the proton peaks of pure PDMAPMAm; 35 more importantly, the characteristic peaks of 3.28 ppm (h) and 2.76 ppm (g) with triple peaks can be ascribed to H h (NH 2 CH 2 CH 2 −) and H g (−CH 2 CH 2 S−), which correspond to the characteristic peaks of AET•HCl, demonstrating that the NH 2 -end PDMAPMAm was prepared successfully.…”

Synthesis and Applications of Carboxymethyl Cellulose Hydrogels

“…Ph-sensitive spray-dried microspheres prepared from a polyacrylamide–sodium carboxymethyl cellulose (PAAMG–CMC–Na) co-polymer can be used for colon-targeted delivery. The microspheres prepared by Vijaykumar et al using natural CMC–Na as a carrier could not prevent the drug release in the stomach and small intestine [ 49 ]. However, upon grafting the microspheres onto the PAAmg polymer to improve the CMC–Na function and converting the amide functional group of PAAmg to a carboxyl group, the CMC–Na co-polymer became pH-sensitive.…”