Binding and encapsulation of doxorubicin on smart hydrogels for oral delivery

BOSIO VALERIA E.; MACHAIN VICTORIA; PEREZ DE VERTI, I.; GOMEZ LOPEZ AZUCENA; MARCHETTI SERGIO G.; MAGDALENA MECHETTI; GUILLERMO R. CASTRO

Trivandrum

Conferencia; International Conference on New Horizons in Biotechnology; 2011

Smart hydrogels based on biopolymers are becoming increasingly attractive in many technological applications such as drug delivery. Controlled release technologies have the advantage of reducing the drug release rate, keeping the drug and time release constant, avoiding deleterious side effects and increase drug efficiency. Complex formation amongst the cargo and biopolymer is required as first step to encapsulate drugs. Pectins (Pect) with 33 to 74% methoxilation degree were tested with doxorubicin (Dox), a very high toxic and widely drug used in many cancer therapies. Pect 35 and 55% were selected because of higher than 50 % Dox binding. Pect microspheres of 35 and 55% obtained by ionotropic gelation have 66 and 88 % Dox loading. Kinetic release studies of Dox showed 75 and 55% drug release from 35 and 55% respectively, at pH 7.4, 25ºC during 180 min. Besides, the Dox release decrease to 27% in Pect 55% microspheres after one year storage at 4 ºC under the same experimental conditions. FTIR analysis of Pect-dox complex showed hipsochromic shifts for the sC=O, dN-H and sC-C vibrational modes compared to Dox spectrum suggesting an interaction between the cargo and the matrix. Rheological studies of pectins and pectin- dox samples flow behavior exhibited a shear –thinning nature. The viscosity for Pect 55% is higher than the viscosity for Pec 35% for all temperatures studied, and in both cases the viscosity decreased with the increase of temperature. Besides, Pec-Dox samples have higher viscosity values than those of the corresponding Pec samples. However, the viscosity curves as function of shear rate for Pec 35% - Dox are above the curves of Pec 55% - Dox, confirming significant interaction between the cargo and the matrix, which was also established in viscoelastic dynamic.