Binding and Encapsulation of Doxorubicin on Smart Pectin Hydrogels for Oral Delivery

Abstract

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.

Modified bacterial cellulose scaffolds for localized doxorubicin release in human colorectal HT-29 cells

“…In addition, FTIR showed a strong interaction between both polymers, BC and Alg, creating a high interpenetrating biopolymeric network that contributes to enhanced entrapment and loading capacity of hydrophilic drug molecules such as doxorubicin. On the other hand, the ionic interactions of the net negative charges of the carboxylate groups in alginate and the positive net charge in Dox molecules could be responsible for enhancing the loading capability in the nanocomposite film, as previously reported by our laboratory [19]. Besides, hydroxyl groups of cellulose fibers and alginate chains could interact with Dox molecules making hydrogen bonds and stabilizing the drug loading in the coacervate film.…”

“…When BC was reinforced by in situ modification using polymers, such as gelatin, collagen and chitosan for biomedical purposes, novel biophysical film properties were found [18]. In this sense, the addition of negatively charged polymers such as alginates to bacterial cultures during BC synthesis could enhance the interaction between the hybrid films and Dox, as previously reported for the pectin-Dox model [19]. Recently, native or chemically modified BC-alginate composites were found to be versatile systems for mammalian eukaryotic cell cultivation because of the ductility and functionally of nanocellulose-alginate networks [20][21][22].…”

Amide pectin: A carrier material for colon‐targeted controlled drug release

“…In addition, it can form gels in acidic environment allowing various drug delivery formulations (microspheres, beads, pellets, and microparticles) into completely different environments such as nasal, vaginal, ocular, gastric and, large intestine especially, colon. 20,21 However, pectin has not fulfilled its potential for drug delivery systems due to variability on its formulation, which depends on its source and processing that affect to its stability over time and behavior in a hydrated media. In order to improve its properties, such as chemical stability and drug release property, polymerizing pectin polymer with other substance, such as ethyl cellulose, 22 hydroxypropyl methyl cellulose, 23 gelatin, 24 corn protein, 25,26 whey protein, 27 chitosan, 28 or binding with a divalent or trivalent cation to improve the performance of pectin, have been adopted.…”

pH‐responsive hydrogels with dispersed hydrophobic nanoparticles for the oral delivery of chemotherapeutics

“…24–26 Research efforts, in the arena of the oral delivery of doxorubicin, have included polymer nanoparticles, dendrimers, lipid nanocarriers, and smart pectin hydrogels. 27–30 Reducing cardiotoxicity of doxorubicin has also been explored through cardioprotective additives such as steroids, antioxidants, and antidiabetics. 31–34 …”

“…[24][25][26] Research efforts, in the arena of the oral delivery of doxorubicin, have included polymer nanoparticles, dendrimers, lipid nanocarriers, and smart pectin hydrogels. [27][28][29][30] Reducing cardiotoxicity of doxorubicin has also been explored through cardioprotective additives such as steroids, antioxidants, and antidiabetics. [31][32][33][34] In this work, we combined the desirable characteristics of pH-sensitive, hydrophilic networks composed of poly (methyacrylic acid-grafted-ethylene glycol) (P(MAA-g-EG)) with hydrophobic poly(methyl methacrylate) (PMMA) nanoparticles to develop amphiphilic polymer structures for the oral delivery of doxorubicin.…”