Physically Cross-linked Hydrogels of β -cyclodextrin Polymer and Poly(ethylene glycol)-cholesterol as Delivery Systems for Macromolecules and Small Drug Molecules

Abstract

An injectable hydrogel based on the inclusion complexation of polymerized β-cyclodextrin (pβ-CD) and cholesterol terminated poly(ethylene glycol) (PEG-chol) was developed and used as a delivery system for both macromolecules and small drugs. The hydrogel was characterized by different analyses including X-ray diffraction, differential scanning calorimetry and scanning electron microscopy. The effects of pβ-CD/PEG-chol ratio and PEG-chol architecture on the hydrogel properties were also investigated. Cytotoxicity of the hydrogel was evaluated in NIH 3T3 fibroblasts using MTS assay. The hydrogel had an elastic behavior even at high temperature since the gelation temperature was observed at 68 °C. The highest hydrogel strength and stability were observed for the 8-armed PEG-chol at a pβ-CD/PEG-chol ratio of 1:1, w/w. Hydrogel degradation in phosphate buffered saline occurred by gradual erosion over the course of two months. IgG, a model hydrophilic macromolecule and riluzole, a model hydrophobic small drug were incorporated into the hydrogel and quantitatively released in a sustained fashion. The released IgG maintained its bioactivity confirming the absence of deleterious effects on protein structure during loading and release. The hydrogels showed no toxicity on NIH 3T3 fibroblasts confirming their biocompatibility. These results confirm the potential of pβ-CD/PEG-chol hydrogel as a versatile delivery system for drugs of different molecular weights and nature.

Injectable Hydrogels Based on Cyclodextrin/Cholesterol Inclusion Complexation and Loaded with 5-Fluorouracil/Methotrexate for Breast Cancer Treatment

“…In contrast, formula B did not show any cross-over point because the values of G > G for the whole rheogram, which indicates the viscous behaviors of the system. This finding and interpretation were in agreement with previously reported data, where PEG-chol exhibits a higher affinity to β-CD when compared with PEG-Ad [34].…”

Injectable and protease-degradable hydrogel for siRNA sequestration and triggered delivery to the heart

“…The hydrophobic host cavity of CD has been well described in hydrogel systems, where it can be used to interact with other hydrophobic molecules, or guests, in supramolecular complexes [42,47]. Of these guests, cholesterol has been one of the most commonly described, where its ability to complex CD has been used for a variety of biomaterial applications [48–50]. Thus, we hypothesized that CD inclusion would sequester cholesterol-modified siRNAs and attenuate their passive release from hydrogels, paralleling previous reports of the use of CD to retain and sustain small molecule release [42,47].…”

Fabrication of β-cyclodextrin-mediated single bimolecular inclusion complex: characterization, molecular docking, in-vitro release and bioavailability studies for gefitinib and simvastatin conjugate

“…Multimolecular inclusion complex formation has been the main objective of our study which has been successfully accomplished as suggested by the entrapment ratio of gefitinib and simvastatin as 3 ± 0.48 : 2 ± 0.19. Earlier reports are there to formulate individual molecules of the aforementioned drugs as monomolecular inclusion complex; however, this is the first approach to manufacture single inclusion complex containing more than one drug molecule which would be cost effective and rapid in its action than conventional method of cross‐linking of BCD monomers. The characterization of the inclusion complex by different methods such as FT‐IR, DSC, XRD and DLS further confirmed that there is a formation of inclusion complex of both the drugs with BCD.…”

“…In pursuit, we are currently working on this process to upregulate both gefitinib and simvastatin release significantly through our microparticles. Although previous authors acknowledged that cross‐linked β‐cyclodextrins, hydrogels or nanosponges could offer value added release to drugs and that seems to be an alternate route to increase such solubilities; these methods often fall costlier due to the expensive cross‐linking polymers involved herewith. Moreover, such processes are tedious due to cross‐linking reaction with the polymeric agents, maintaining its specificity and eliminating its toxic by‐products.…”