Self‐assembling cyclodextrin based hydrogels for the sustained delivery of hydrophobic drugs

Abstract

This study aims to investigate the rheological properties of self-assembling gels containing cyclodextrins with potential application as injectable matrix for the sustained delivery of poorly soluble drugs. The ability of these gels to entrap two hydrophobic molecules, benzophenone (BZ) and tamoxifen (TM), and to allow their in vitro sustained release was evaluated. In view of their future pharmaceutical use, gels were sterilized by high hydrostatic pressures (HHP) and tested for their biocompatibility. The gels formed instantaneously at room temperature, by mixing the aqueous solutions of two polymers: a beta-cyclodextrin polymer (pbetaCD) and a hydrophobically modified dextran by grafting alkyl side chains (MD). MD-pbetaCD gels presented a viscoelastic behavior under low shear, characterized by constant values of the loss modulus G'' and the storage modulus G'. The most stable gels were obtained for a total polymer concentration C(p) of 6.6% and 7.5% (w/w), and a polymer ratio MD/pbetaCD of 50/50 and 33/67 (w/w). BZ and TM were successfully incorporated into MD-pbetaCD gels with loading efficiencies as high as 90%. In vitro, TM and BZ were released gradually from the gel matrix with less than 25% and 75% release, respectively, after 6 days incubation. HHP treatment did not modify the rheological characteristics of MD-pbetaCD gels. Moreover, the low toxicity of these gels after intramuscular administration in rabbits makes them promising injectable devices for local delivery of drugs.

Cyclodextrin Complexation for Affinity‐Based Antibiotic Delivery

“…More recently, hydrophobically modified dextran and cyclodextrin self‐assembled gels have been developed for sustained release of hydrophobic drugs 30. However, these gels are not stable and start to disintegrate in buffer if they will be kept more than a week, making them unsuitable for long‐term delivery.…”

Cyclodextrin-based supramolecular systems for drug delivery: Recent progress and future perspective

“…Compared with nonionic counterparts, charged CD polymers have additional electrostatic interactions with oppositely charged guest molecules to achieve a synergetic effect [67]. This type of CD-based polymers has been widely employed to construct nanospheres, nanogels or hydrogels, and nanocapsules, via host-guest interaction mediated self-assembly in the presence of guest molecules including hydrophobic drugs, hydrophobically modified hydrophilic polymers, and hydrophobic polymers [68-74]. Nevertheless, polymers thus obtained generally exhibit branched structure and broad molecular weight distribution.…”

“…The formation of these supramolecular hydrogels is largely driven by inclusion complexation between the CD units and hydrophobic groups. Hydrogels can be instantaneously formed at room temperature by mixing β-CD polymers or β-CD conjugated polymers with hydrophobically modified hydrophilic polymers such as PEG, dextran, chitosan, and hyaluronic acid, which can sustain the release of proteins or hydrophobic drugs [74, 97, 193-195]. Based on host-guest recognition between β-CD and cholesterol inclusion, Hennink's group fabricated self-assembling hydrogels utilizing 8-arm star shaped PEG modified with either β-CD or cholesterol via a succinyl linker that is hydrolytically cleavable.…”

Hidrogeles de ciclodextrinas para administración de fármacos

“…Cuando se mezclan disoluciones acuosas de ambos polímeros en concentraciones de 6.6-7.5% p/p se observa una inmediata separación de fases. La fase gel presenta una alta concentración de ambos polímeros, con valores de G´ y G´´ 400-500 Pa y 1200-1400 Pa, respectivamente [81,82]. Si las concentraciones de polímeros son más bajas (0.1-1% p/p) se forman partículas nanométricas de tamaño variable según el grado de sustitución del polímero con grupos que forman complejos con las CDs [83,84].…”

“…Una ligera presión causa la decomplejación y un descenso de la viscosidad, y el sistema fluye fácilmente. Al cesar la presión, los geles recuperan rápidamente los valores iniciales de G´ y G´´ [81]. Estas propiedades junto con una excelente biocompatibilidad permiten augurar a estos sistemas de gelificación in situ un futuro muy prometedor en el campo de la biomedicina.…”