Improved oral delivery of resveratrol using proliposomal formulation: investigation of various factors contributing to prolonged absorption of unmetabolized resveratrol.
OBJECTIVE
The objective of this study was to design lipid-based formulation to enhance the absorption of unmetabolized resveratrol (RSV) over adequate time and investigate various factors that contribute to prolonged absorption of RSV.


METHODS
Proliposomal formulations containing distearoyl phosphatidyl choline (DSPC) with or without cholesterol were prepared and evaluated. The liposomes obtained from hydration of proliposomal mixture were evaluated for size, zeta, physical appearance and entrapment. The integrity of liposomes in bile salt solution and solubility of RSV in sodium taurocholate solution in the presence of various concentrations of DSPC were evaluated to assess the stability and in varied gastrointestinal conditions. Finally, oral pharmacokinetic studies of liposomal dispersions in comparison with RSV solution were evaluated.


RESULTS
Results revealed that spontaneous formation of liposomes did not occur upon hydration of RSV: DSPC proliposomes rather showed tendency to form loose cotton-like aggregates. Cholesterol aided in the formation of stable liposomes with large negative zeta potential. Release of RSV from liposomes in the presence of taurocholate was dependent on the amount and type of total lipid. Liposomes without cholesterol showed faster release, and release increased as the amount of DSPC in the formulation increased. Solubility studies indicated that DSPC increases the solubility of RSV in the presence of sodium taurocholate, and corroborates that bilayer assembly is disrupted because of interaction between RSV and DSPC. Mixture of RSV:DSPC:Chol at 1:0.25:0.25 formed stable colloidal dispersion with zeta potential -22 and released only 20 - 23% of entrapped RSV when incubated with 20 mM sodium taurocholate. Pharmacokinetic profile revealed that AUC and Cmax were twofold higher than plain RSV.


CONCLUSIONS
The proliposomal formulation optimized by considering various physicochemical factors and simulated in vitro testing result in significant improvement rate and extent of absorption of unmetabolized RSV.
Western University of Health Sciences, Western Centre for Drug Development , Pomona, California , USA.
Siddalingappa
S
Basavaraj
Guru V
GV
Betageri
D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers / Q000737:chemistry*; D007408:Intestinal Absorption / Q000502:physiology*; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D010316:Particle Size; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D012995:Solubility; D013267:Stilbenes / Q000008:administration & dosage* / Q000493:pharmacokinetics
D000975:Antioxidants; D004337:Drug Carriers; D008081:Liposomes; D010975:Platelet Aggregation Inhibitors; D013267:Stilbenes; D000077185:Resveratrol