Blend Hydrogel Microspheres of Carboxymethyl Chitosan and Gelatin for the Controlled Release of 5-Fluorouracil

Abstract

Carboxymethyl chitosan (CMCS) was synthesized and blended with gelatin (GE) to prepare hydrogel microspheres by w/o emulsion cross-linking in the presence of glutaraldehyde (GA), which acted as a cross-linker. 5-Fluorouracil (5-FU) was encapsulated to investigate its controlled release (CR) characteristics in acidic (pH 1.2) and alkaline (pH 7.4) buffer media. The microspheres which formed were spherical in nature, with smooth surfaces, as judged by the scanning electron microscopy (SEM). Fourier transform infrared spectroscopy (FTIR) confirmed the carboxymethylation of CS and the chemical stability of 5-FU in the formulations. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) confirmed the physical state and molecular level dispersion of 5-FU. Equilibrium swelling of microspheres was performed in water, in order to understand the water uptake properties. The in vitro release of 5-FU was extended up to 12 h in pH 7.4 phosphate buffer, revealing an encapsulation efficiency of 72%. The effects of blend composition, the extent of cross-linking, and initial drug loading on the in vitro release properties, were investigated. When analyzed through empirical equations, the release data suggested a non-Fickian transport mechanism.

Development and In Vitro Evaluation of 5-Fluorouracil-Eluting Stents for the Treatment of Colorectal Cancer and Cancer-Related Obstruction

“…XRD patterns of pure 5FU, and PU and PU 5FU coatings were recorded ( Figure 3 ) and d -spacing values were determined for prominent peaks ( SI, Table S4 ). Pure 5FU revealed a series of characteristic diffraction peaks consistent with those reported previously [ 42 , 56 , 59 , 61 , 69 , 70 ], with a prominent 2 θ peak at 28.6° corresponding to a d -spacing of 3.123 Å. The diffractogram of the PU coating revealed a broad 2 θ peak at 19.9° and a low intensity 2 θ peak at 29.2°, which are consistent with previous literature reports and can be attributed to amorphous and semicrystalline segmented polycarbonate-PUs [ 43 , 71 , 72 ].…”

“…DSC was used to investigate the presence of 5FU crystallites within the PU matrix and possible changes in the thermal properties of the PU after drug incorporation. The thermogram of pure 5FU revealed a sharp endothermic peak at 282 °C corresponding to its melting ( Tm ) and degradation temperatures ( Td ) ( Figure 6 ) [ 32 , 59 , 61 ], whereas the thermogram of PU film displayed a glass transition temperature ( Tg ) of ~106 °C, which is consistent with interactions between hard urethane segments [ 62 , 76 ]. In comparison, the thermogram of PU 5FU films revealed a small, sharp endothermic peak at 285 °C consistent with the 5FU Tm and a Tg at ~99 °C.…”

“…To examine the distribution and interactions of 5FU within the stents, PA-FTIR spectroscopy was performed on coatings prepared on silicon wafers ( Figure 2 ). The spectrum of pure 5FU exhibited characteristic peaks at ~2940, 1740, 1250 and 1230 cm −1 consistent with C–H, C=O, C–N and C–F stretching vibrations, respectively, and at ~825 cm −1 consistent with C-H deformation [ 32 , 59 , 60 , 61 ]. For PU coatings (drug-free), the spectrum revealed peaks at ~3330, 2930, 1740 and 1270 cm −1 corresponding to N–H, C–H, C=O and C–O stretching vibrations, and consistent with the reported aliphatic polycarbonate-PU structure [ 62 , 63 , 64 , 65 ].…”

<p>Burgeoning Polymer Nano Blends for Improved Controlled Drug Release: A Review</p>

“…The blended microspheres were examined with different analytical techniques to understand the interaction of the polymer and 5-FU. As a result, the in vitro release of 5-FU increased to 12 h at a physiological pH, 82 with an expected enhancement for nanospheres.…”

Folic Acid‐Navigated and β‐Cyclodextrin‐Decorated Carbon‐Encapsulated Iron Nanoparticles as the Nanotheranostic Platform for Controlled Release of 5‐Fluorouracil

“…The controlled release of a drug may lower its side effects and increases its therapeutic effect on tumors. The complexation of 5‐FU or its derivatives (for example tegafur) inside βCD attached to polymeric vectors, carbon materials, or iron oxide nanoparticles, were reported. The in vitro or in vivo studies revealed the therapeutic potential of the designed 5‐FU delivery platforms.…”