Preformulation Studies and Bioavailability Enhancement of Curcumin with a ‘Two in One’ PEG-β-Cyclodextrin Polymer

Abstract

Drug delivery systems are used to improve the biopharmaceutical properties of curcumin. Our aim was to investigate the effect of a water-soluble ‘two in one’ polymer containing covalently bonded PEG and βCD moieties (βCPCD) on the solubility and bioavailability of curcumin and compare it to a polymeric β-cyclodextrin (βCDP) cross-linked with epichlorohydrin. Phase-solubility and dynamic light scattering (DLS) experiments showed that the solubility of curcumin increased significantly in 10 m/m % βCPCD and βCDP solutions, but βCPCD–curcumin particles had higher hydrodynamic volume. The formation of the βCPCD–curcumin complex in solution and sedimented phase was confirmed by NMR spectroscopy. Biocompatibility and permeability experiments were performed on Caco-2 cells. Polymers did not show cytotoxicity up to 10 m/m % and βCPCD significantly increased the permeability of curcumin. DLS measurements revealed that among the interaction of polymers with mucin, βCPCD formed bigger aggregates compared to βCDP. Curcumin complexes were lyophilized into capsules and structurally characterized by micro-CT spectroscopy. Drug release was tested in a pH 1.2 medium. Lyophilized complexes had a solid porous matrix and both βCPCD and βCDP showed rapid drug release. βCPCD provides an opportunity to create a swellable, mucoadhesive matrix system for oral drug delivery.

Recent Options and Techniques to Assess Improved Bioavailability: In Vitro and Ex Vivo Methods

“…The standard method used to differentiate Caco-2 cells is to seed them on a microporous surface, such as polycarbonate cell culture inserts. On the supporting surface, the cells grow and form a monolayer with tight junctions among the neighboring cells; therefore, an apical and basal compartment is created (Figure 1) [35,36]. Permeability or transport studies are performed by adding the drug or formulation to the apical chamber and detecting its concentration in the basal chamber.…”

“…Additionally, the transepithelial electrical resistance (TEER) should be monitored on a regular basis using a volt-ohmmeter equipped with a "chopstick" electrode [38,39]. The integrity of the Caco-2 monolayer can be considered sufficient if the TEER values are at least 800-900 Ω cm 2 [35,36]. This must be checked before and after the transport experiment well by well [38].…”

Recent Advances in Micro- and Nano-Drug Delivery Systems Based on Natural and Synthetic Biomaterials

“…Effective interactions, such as hydrogen bonding and physical entanglements, manifest themselves at the point of contact [216]. According to Haimhoffer et al [217] the mucoadhesive properties of the polymer were improved by the incorporation of free PEG chains into crosslinked PHEMA particles. These chains served as adhesion promoters.…”

A Review of Cyclodextrin Encapsulation and Intelligent Response for the Release of Curcumin

“…The resulting curcumin-cyclodextrin polymers exhibited higher anti-proliferative activity against A375 cells, compared to free CUR. In another study by Haimhoffer et al, polyethylene glycol was used as a cross-linking agent for CDs to form ternary complexes with CUR [66]. The resulting CD polymer effectively delivered the complexed CUR to the cell membrane, which improved the CUR permeability significantly more than the CD polymer cross-linked with encapsulation.…”