Development and Evaluation of Tannic Acid-Coated Nanosuspension for Enhancing Oral Bioavailability of Curcumin

Abstract

Curcumin (CUR) has been used in the treatment of various diseases such as cough, fever, skin disease, and infection because of various biological benefits such as anti-inflammatory, antiviral, antibacterial, and antitumor activity. However, CUR is a BCS class 4 group and has a limitation of low bioavailability due to low solubility and permeability. Therefore, the purpose of this study is to prepare a nanosuspension (NSP) loaded with CUR (CUR-NSP) using a statistical design approach to improve the oral bioavailability of CUR, and then to develop CUR-NSP coated with tannic acid to increase the mucoadhesion in the GI tract. Firstly, the optimized CUR-NSP, composed of sodium dodecyl sulfate (SDS) and polyvinylpyrrolidone/vinyl acetate (PVP/VA), was modified with tannic acid (TA). The particle size and polydispersity index of the formulation measured by laser scattering analyzer were 127.7 ± 1.3 nm and 0.227 ± 0.010, respectively. In addition, the precipitation in distilled water (DW) was 1.52 ± 0.58%. Using a differential scanning calorimeter and X-ray diffraction analysis, the stable amorphous form of CUR was confirmed in the formulation, and it was confirmed that CUR-NSP formulation was coated with TA through a Fourier transform-infrared spectroscopy. In the mucoadhesion assay using the turbidity, it was confirmed that TA-CUR-NSP had higher affinity for mucus than CUR-NSP under all pH conditions. This means that the absorption of CUR can be improved by increasing the retention time in the GI tract of the formulation. In addition, the drug release profile showed more than 80% release, and in the cellular uptake study, the absorption of the formulation (TA-CUR-NSP) containing TA acting as an inhibitor of P-gp was increased by 1.6-fold. In the evaluation of antioxidant activity, the SOD activity of TA-CUR-NSP was remarkably high due to TA, which improves cellular uptake and has antioxidant activity. In the pharmacokinetic evaluation, the maximum drug plasma concentration of the TA-coated NSP formulation was 7.2-fold higher than that of the pure drug. In all experiments, it was confirmed that the TA-CUR-NSP is a promising approach to overcome the low oral bioavailability of CUR.

Glutathione-Responsive Tannic Acid-Assisted FRET Nanomedicine for Cancer Therapy

“…The polymer alone (in absence of TA) was unable to form such stable, smaller-sized particles with a narrow size distribution. Such a strategy of preparing a stable nano-formulation with more than one drug, employing combination therapy, could be a useful and better alternative than TA-assisted nano-formulation containing only one drug, as in previous reports [ 49 , 51 ]. During such nanoparticle formation by the amphiphilic polymer, lipophilic drugs may form the hydrophobic core of the nanoparticle.…”

“…The preparation of such a water-soluble drug-conjugated PEG-based polymer by converting the drug into an inactive but more stable prodrug form will allow it to revert to the pharmacologically active agent in presence of any biological stimulus [ 13 , 33 , 41 , 43 , 45 ]. Furthermore, tannic acid (TA), one of many naturally occurring dietary polyphenolic compounds derived from plant sources and a subset of hydrolyzable tannin congeners, has shown its excipient value in pharmaceutics [ 49 , 50 , 51 , 52 ]. Recently, TA has successfully been used as an additive molecule due to its high water solubility, low viscosity, high biocompatibility, crosslinked network-forming ability via hydrogen bonds, and successful binding ability to drug molecules via hydrophobic interactions [ 53 , 54 , 55 ].…”

“…Recently, TA has successfully been used as an additive molecule due to its high water solubility, low viscosity, high biocompatibility, crosslinked network-forming ability via hydrogen bonds, and successful binding ability to drug molecules via hydrophobic interactions [ 53 , 54 , 55 ]. Such properties of TA have allowed it to be used to improve the solubilization of various hydrophobic drugs (curcumin, paclitaxel, amphotericin B, rapamycin, or docetaxel) inside the drug delivery system for localized delivery through a parenteral route [ 49 , 51 ]. Considering its benefits, we have used TA as a biocompatible additive for dual drug-conjugated PEG-based polymers to generate the stable nano-formulations in water and thereby develop a possible FRET system between these two drug molecules CPT (FRET donor) and CUR (FRET acceptor).…”

"Optimizing Pharmaceutical Formulations: Advancements in Nanosuspension Pre-Formulation to Enhance Solubility and Bioavailability of Active Agents"

“…In the pre-formulation analysis of nepafenac, a calibration curve was established to ensure the highest quality of the drug and accurate assessment of its characteristics [10][11][12][13][14]. This involved rigorous testing, including sensory analysis to evaluate hue, scent, and visual attributes.…”

Pickering Emulsions Enhance Oral Bioavailability of Curcumin Nanocrystals: The Effect of Oil Types

“…Consequently, the application of NCs has been extended to oral delivery of BCS IV drugs recently [ 2 , 9 , 10 ]. For example, 1.25–~7 folds enhancement in oral bioavailability of curcumin (CUR) has been achieved by NCs [ 11 , 12 , 13 ]. However, dissolution would decrease the number of intact NCs in the gastrointestinal tract and impair the oral bioavailability of BCS IV drugs.…”