Nanoemulsion for improving solubility and permeability of Vitex agnus-castus extract: formulation and in vitro evaluation using PAMPA and Caco-2 approaches.
The purpose of this study was to develop new formulation for an improved oral delivery of Vitex agnus-castus (VAC) extract. After the optimization and validation of analytical method for quali-quantitative characterization of extract, nanoemulsion (NE) was selected as lipid-based nanocarrier. The composition of extract-loaded NE resulted in triacetin as oil phase, labrasol as surfactant, cremophor EL as co-surfactant and water. NE contains until 60 mg/mL of extract. It was characterized by DLS and TEM analyses and its droplets appear dark with an average diameter of 11.82 ± 0.125 nm and a polydispersity index (PdI) of 0.117 ± 0.019. The aqueous solubility of the extract was improved about 10 times: the extract is completely soluble in the NE at the concentration of 60 mg/mL, while its solubility in water results less than 6 mg. The passive intestinal permeation was tested by using parallel artificial membrane permeation assay (PAMPA) and the permeation across Caco-2 cells after preliminary cytotoxicity studies were also evaluated. NE shows a good solubilizing effect of the constituents of the extract, compared with aqueous solution. The total amount of constituents permeated from NE to acceptor compartment is greater than that permeated from saturated aqueous solution. Caco-2 test confirmed PAMPA results and they revealed that NE was successful in increasing the permeation of VAC extract. This formulation could improve oral bioavailability of extract due to enhanced solubility and permeability of phytocomplex.
a Department of Chemistry, University of Florence , Sesto Fiorentino , FI , Italy and.
Vieri
V
Piazzini
a Department of Chemistry, University of Florence , Sesto Fiorentino , FI , Italy and.
Elena
E
Monteforte
b NEUROFARBA, Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmacology and Toxicology, University of Florence , Florence , Italy.
Cristina
C
Luceri
b NEUROFARBA, Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmacology and Toxicology, University of Florence , Florence , Italy.
Elisabetta
E
Bigagli
a Department of Chemistry, University of Florence , Sesto Fiorentino , FI , Italy and.
Anna Rita
AR
Bilia
a Department of Chemistry, University of Florence , Sesto Fiorentino , FI , Italy and.
Maria Camilla
MC
Bergonzi
D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004339:Drug Compounding; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism*; D004655:Emulsions; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology; D008567:Membranes, Artificial; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism*; D010316:Particle Size; D010539:Permeability / Q000187:drug effects; D012995:Solubility / Q000187:drug effects; D020950:Vitex
D004365:Drugs, Chinese Herbal; D004655:Emulsions; D008567:Membranes, Artificial; C553090:Vitex agnus castus extract
Caco-2; Nanoemulsion; PAMPA; Vitex agnus-castus L.; solubility