In the current study, a pH sensitive intelligent hydroxypropyl–β–cyclodextrin-based polymeric network (HP-β-CD-g-MAA) was developed through a solution polymerization technique for site specific delivery of cytarabine in the colonic region. Prepared hydrogel formulations were characterized through cytarabine loading (%), ingredient’s compatibility, structural evaluation, thermal integrity, swelling pattern, release behavior and toxicological profiling in rabbits. Moreover, the pharmacokinetic profile of cytarabine was also determined in rabbits. New polymer formation was evident from FTIR findings. The percentage loaded into the hydrogels was in the range of 37.17–79.3%. Optimum swelling ratio of 44.56 was obtained at pH 7.4. Cytarabine release was persistent and in a controlled manner up to 24 h. In vitro degradation of hydrogels was more pronounced at intestinal pH as compared to acidic pH. Toxicity studies proved absence of any ocular, skin and oral toxicity, thus proving biocompatibility of the fabricated network. Hydrogels exhibited longer plasma half-life (8.75 h) and AUC (45.35 μg.h/mL) with respect to oral cytarabine solution. Thus, the developed hydrogel networks proved to be excellent and biocompatible cargo for prolonged and site-specific delivery of cytarabine in the management of colon cancer.

In the present study, pH-sensitive, biodegradable, and biocompatible Na-CMC/pectin poly(methacrylic acid) hydrogels were synthesized using an aqueous free radical polymerization technique and encapsulated by cytarabine (anti-cancer drug). The aim of the project was to sustain the plasma profile of cytarabine through oral administration. Sodium carboxymethyl cellulose (Na-CMC) and pectin were cross-linked chemically with methacrylic acid (MAA) as a monomer, using methylene bisacrylamide (MBA) as cross-linker and ammonium per sulfate (APS) as an initiator. Prepared hydrogel formulations were characterized for their texture, morphology, cytarabine loading efficiency, compositional and structural properties, thermal nature, stability, swelling response, drug release profile (pH 1.2 and pH 7.4), and in-vivo pharmacokinetic evaluation. Cytarabine-loaded hydrogels were also evaluated for their safety profile by carrying out toxicity studies in rabbits. Results demonstrated efficient encapsulation of cytarabine into the prepared network with loading ranging from 48.5–82.3%. The highest swelling ratio of 39.38 and maximum drug release of 83.29–85.27% were observed at pH 7.4, highlighting the pH responsiveness of the grafted system. Furthermore, cytarabine maximum release was noticed over 24 h, ensuring a sustained release response for all formulations. Histopathological studies and hemolytic profiles confirmed that the prepared hydrogel system was safe, biocompatible, and non-irritant, showing no symptoms of any toxicities and degeneration in organs. Moreover, pharmacokinetic estimation of the cytarabine-loaded hydrogel showed a remarkable increase in the plasma half-life from 4.44 h to 9.24 h and AUC from 22.06 μg/mL.h to 56.94 μg/mL.h. This study revealed that the prepared hydrogel carrier system has excellent abilities in delivering the therapeutic moieties in a controlled manner.

The journal retracts the article “Development and Evaluation of Cellulose Derivative and Pectin Based Swellable pH Responsive Hydrogel Network for Controlled Delivery of Cytarabine”