Tailoring doxorubicin sustainable release from biopolymeric smart matrix using congo red as molecular helper.

Doxorubicin (Dox) was co-encapsulated with congo red (CR) in order to increase drug encapsulation and sustain the release from gel microbeads composed of alginate-carboxy methyl guar gum (68/32) for oral controlled delivery. No release of either cargo molecule from the microbeads at pH 1.2 within 90 minutes was detected. However, 62% CR and 16% Dox were released from the gels at pH 7.4 at 37 °C in 8 hours when both the cargo molecules were studied alone. Presence of CR in the formulation reduces the release of Dox by about 25-30% under the same experimental conditions. Rheological properties of the formulations have been investigated at different temperatures between 20 and 37 °C. Shear thinning behavior was observed by steady-shear flow experiments for all formulations, and no yield stress was observed for any of the formulations. The temperature effect on Alg-CMGG-Dox-CR evidenced a synergic action between Dox and CR. Dynamic frequency sweep tests were performed to study the viscoelastic properties of the formulations. The patterns observed for Alg-CMGG indicated physical gel characteristics; however, all other formulations showed behaviour typical of concentrated solutions. These results confirm the interaction of Dox and CR, and the concomitant positive effect on sustainable release in oral delivery.

Binding and encapsulation of doxorubicin on smart pectin hydrogels for oral delivery.

Pectins (Pec) of 33 to 74 % esterification degree were tested with doxorubicin (Dox), a very high toxic drug widely used in cancer therapies. Pec with 35 and 55 % DE were selected because of the Dox binding higher than Pec microspheres of 35 and 55 % obtained by ionotropic gelation with Ca⁺² have 88 and 66 % Dox loading capacity. Kinetic Dox release showed more than 80.0 and about 30.0 % free drug from 35 % and 55 % Pec formulations at pH 7.4, and 37 °C after 1-h incubation, respectively. Besides, Dox release decrease to 12 % in 55 % Pec microsphere formulation after 1-year storage at 4 °C. FTIR analysis of Pec-Dox complex showed hipsochromic shifts for the σ(C=O), δ(N-H) and σ(C-C) vibrational modes compared to Dox spectrum suggesting strong interaction between the drug cargo and the matrix. Rheological studies of Pec and Pec-Dox samples flow behavior exhibited a shear-thinning nature. Fifty-five percent of Pec showed higher viscosity than the viscosity for 35 % Pec in all range of temperatures analyzed, and decreased when the temperature is raised. Besides, Pec-Dox complexes have higher viscosity values than those of the corresponding Pec samples, and viscosity curves as function of shear rate for 35 % Pec-Dox are above the curves of 55 % Pec-Dox. In both cases, the results are confirming significant interaction between the cargo and the matrix, which also was established in viscoelastic dynamic analysis.

Controlled release of sulfasalazine release from "smart" pectin gel microspheres under physiological simulated fluids.

Sulfasalazine (SLZ) is a synthetic nonsteroidal anti-inflammatory drug used mainly for the treatment of an inflammatory bowel and other diseases. Two pectins with different methylation degrees were blended to synthesized gel microspheres by ionotropic gelation for SLZ encapsulation. The encapsulation efficiency was found to be around of 99% in all formulations tested. However, different SLZ release profiles related to the methylation degrees of pectin were observed. Mixture of low methylated (LM) and high methylated (HM) pectins in the presence of calcium(II) displayed the best microsphere morphologies among the formulations tested determined by optical and electronic microscopies. The percentage of drug release using a mixture of LM and HM pectins after 255 min in simulated gastric fluid (pH = 1.2), simulated intestinal fluid (pH = 6.8), and phosphate buffer (pH = 7.4) were 15.0%, 47.0%, and 52.2%, respectively.