New cyclodextrin hydrogels cross-linked with diglycidylethers with a high drug loading and controlled release ability.
OBJECTIVE
The goal of the study is to develop new hydrogels based on cyclodextrins cross-linked with ethyleneglycol diglycidylether (EGDE) under mild conditions, to be used as carriers of amphiphilic drugs. Also, it aims to characterize the cross-linking and the drug loading and release processes.


METHODS
The cross-linking of hydroxypropyl-beta-cyclodextrin (HPbetaCD) with EGDE, in the absence or presence of hydroxypropylmethylcellulose (HPMC) Methocel K4M, was optimized applying oscillatory rheometry and Fourier transform infrared. Hydrogels were characterized regarding swelling in water, ability to load diclofenac, and release after different drying treatments.


RESULTS
Solutions of HPbetaCD (14.28%), without or with HPMC (0.2-1.0%), provided firm and transparent hydrogels after cross-linking with EGDE (14.28%), in which around two thirds of the OH groups were cross-linked. The incorporation of HPMC progressively reduced the gel time and the swelling degree of hydrogels. HPbetaCD hydrogels efficiently loaded diclofenac and sustained the release for several hours. The presence of HPMC slowed the release from swollen hydrogels, but promoted it from hydrogels dried before the loading and also before the release.


CONCLUSIONS
HPbetaCD hydrogels with good mechanical properties and tunable loading and release ability can be obtained by direct cross-linking with EGDE.
Rodriguez-Tenreiro
Carmen
C
Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782, Santiago de Compostela, Spain.
Alvarez-Lorenzo
Carmen
C
Rodriguez-Perez
Ana
A
Concheiro
Angel
A
Torres-Labandeira
Juan J
JJ
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000465:Algorithms; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry; D003432:Cross-Linking Reagents; D003505:Cyclodextrins / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004008:Diclofenac / Q000008:administration & dosage / Q000737:chemistry; D020100:Hydrogels / Q000737:chemistry*; D010078:Oxazines; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D012212:Rheology; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman; D047392:beta-Cyclodextrins / Q000737:chemistry
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003432:Cross-Linking Reagents; D003505:Cyclodextrins; D003692:Delayed-Action Preparations; D020100:Hydrogels; D010078:Oxazines; D004364:Pharmaceutical Preparations; D047392:beta-Cyclodextrins; D004008:Diclofenac; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C071191:MK 458