Efficient Loading and Controlled Release of Benzophenone-3 Entrapped into Self-Assembling Nanogels

Samia      Daoud-Mahammed; Sunil      A. Agnihotri; Kawthar      Bouchemal; Stefanie      Kloters; Patrick      Couvreur; Ruxandra      Gref

Abstract

Benzophenone-3 (BZ-3), was successfully entrapped into nanogels prepared by a simple one-step method based on selfassembly of two water soluble polymers: a hydrophobically modified dextran (MD) and a β-Cyclodextrin polymer (pβ-CD). Isothermal titration microcalorimetry (ITC) and phase solubility experiments were performed at 4, 25 or 37°C to investigate the interaction of the hydrophobic BZ-3 with MD and pβ-CD. The BZ-3 entrapment efficiency, yield of nanogels formation, particle size, and BZ-3 release were also evaluated. BZ-3/pβ-CD interaction was characterized by association constants K= 5180 M-1 and K´= 2700 M-1, as determined by phase solubility and ITC experiments, respectively. Differences obtained in association constants values were discussed critically. Results indicate that both K and K´ decrease with increase in temperature. The strong interactions between BZ-3 and pβ-CD were characterized by a negative enthalpy change ( H) with entropic contribution (T S). Monodisperse nanogels were produced with an entrapment up to 75 % and yield up 84 %. BZ-3 was firmly entrapped into nanogels, as only the dilution of the nanogels led to its release. This system provides an advantage for sunscreen formulation to prevent systemic penetration of BZ-3. The ‘green’ (solvent free) preparation method, and the possibility of unlimited storage after freeze drying makes these nanogels valuable candidates for the entrapment of sun screen agents.

Keywords: Nanogels, cyclodextrins, inclusion complexes, sunscreen, isothermal titration microcalorimetry, drug loading, sunscreen agents, UV rays, photoprotection, photo-sensitivity, permeability, modified dextran, centrifugation, supernatant, QELS, CDs, solubilization, MD, nanogel, thermodynamic, enthalpy, entropy, Temperature