title: Self-emulsifying phospholipid pre-concentrates (SEPPs) for improved oral delivery of the anti-cancer genistein: Development, appraisal and ex-vivo intestinal permeation.
abstract: Genistein (GEN), a potent anticancer agent, suffers from scanty oral bioavailability due to poor solubility and extensive metabolism. This work endeavored to enhance GEN solubility and intestinal permeability via fabrication of self-emulsifying phospholipid pre-concentrates (SEPPs) using some bioactive surfactants. Moreover, the potential of surfactant-free SEPP to address GEN obstacles was investigated. SEPPs were prepared from Phosal(®) 53MCT, oil/phosphatidylcholine mixture, alone or with only 30% of different surfactant/co-surfactant mixture (S/CO). In-vitro characterization encompassed globule size analysis, zeta potential (ZP), transmission electron microscopy, and in-vitro release. Ex-vivo intestinal permeation study was performed using non-everted rat intestinal sac technique. Upon aqueous dilution, SEPPs were easily dispersed with spherical globules within a nano-range size (from 165±15 to 425±20nm) and adequate negative ZP (>-30mV). SEPPs demonstrated a significant enhancement in GEN release compared to drug suspension without superior effect due to added S/CO. Permeation study revealed that at least 12.13% free GEN was permeated after 120min from SEPPs compared to only 3.7% from drug suspension. Among different SEPPs, SEPP containing 30% Tween 80/Transcutol HP mixture showed the highest GEN permeation (18.54%). Conclusively, SEPP might be a promising nanocarrier that enhances GEN bioavailability via improving dissolution and inhibition of pre-systemic clearance.
authors: Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Egypt.
authors: Eman M M
authors: EM
authors: Shehata
authors: Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Egypt; Department of Pharmaceutics, Faculty of Pharmacy and Drug Manufacturing, Pharos University in Alexandria, Egypt. Electronic address: yosra_pharm@yahoo.com.
authors: Yosra S R
authors: YS
authors: Elnaggar
authors: Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Egypt.
authors: Saly
authors: S
authors: Galal
authors: Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Egypt.
authors: Ossama Y
authors: OY
authors: Abdallah
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics; D065546:Drug Liberation; D004355:Drug Stability; D004655:Emulsions / Q000008:administration & dosage / Q000737:chemistry*; D019833:Genistein / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D008297:Male; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D010743:Phospholipids / Q000737:chemistry*; D051381:Rats; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D010743:Phospholipids; D013501:Surface-Active Agents; D019833:Genistein
keywords: Genistein; Intestinal permeation; Phospholipid; Self-emulsifying