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International journal of nanomedicine
2016;11 4919-4929.

Preparation and evaluation of a self-nanoemulsifying drug delivery system loaded with Akebia saponin D-phospholipid complex.

Jinyang Shen, Jianping Bi, Hongli Tian, Ye Jin, Yuan Wang, Xiaolin Yang, Zhonglin Yang, Junping Kou, Fei Li
Author Information
  1. Jinyang Shen: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing.
  2. Jianping Bi: Shandong Provincial Traditional Chinese Medical Hospital & Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan.
  3. Hongli Tian: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing.
  4. Ye Jin: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing.
  5. Yuan Wang: Traditional Chinese Medical Hospital of Pukou District.
  6. Xiaolin Yang: Key Laboratory of Pharmaceutical and Biological Marine Resources Research and Development of Jiangsu Province, Nanjing University of Chinese Medicine.
  7. Zhonglin Yang: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing.
  8. Junping Kou: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, People's Republic of China.
  9. Fei Li: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing.
PMID: 27713630 DOI: 10.2147/IJN.S108765

Abstract

BACKGROUND: Akebia saponin D (ASD) exerts various pharmacological activities but with poor oral bioavailability. In this study, a self-nanoemulsifying drug delivery system (SNEDDS) based on the drug-phospholipid complex technique was developed to improve the oral absorption of ASD.
METHODS: ASD-phospholipid complex (APC) was prepared using a solvent-evaporation method and characterized by infrared spectroscopy, differential scanning calorimetry, morphology observation, and solubility test. Oil and cosurfactant were selected according to their ability to dissolve APC, while surfactant was chosen based on its emulsification efficiency in SNEDDS. Pseudoternary phase diagrams were constructed to determine the optimized APC-SNEDDS formulation, which was characterized by droplet size determination, zeta potential determination, and morphology observation. Robustness to dilution and thermodynamic stability of optimized formulation were also evaluated. Subsequently, pharmacokinetic parameters and oral bioavailability of ASD, APC, and APC-SNEDDS were investigated in rats.
RESULTS: The liposolubility significantly increased 11.4-fold after formation of APC, which was verified by the solubility test in -octanol. Peceol (Glyceryl monooleate [type 40]), Cremophor EL (Polyoxyl 35 castor oil), and Transcutol HP (Diethylene glycol monoethyl ether) were selected as oil, surfactant, and cosurfactant, respectively. The optimal formulation was composed of Glyceryl monooleate (type 40), Polyoxyl 35 castor oil, Diethylene glycol monoethyl ether, and APC (1:4.5:4.5:1.74, w/w/w/w), which showed a particle size of 148.0±2.7 nm and a zeta potential of -13.7±0.92 mV after dilution with distilled water at a ratio of 1:100 (w/w) and good colloidal stability. Pharmacokinetic studies showed that APC-SNEDDS exhibited a significantly greater 1 (733.4±203.8 ng/mL) than ASD (437.2±174.2 ng/mL), and a greater 2 (985.8±366.6 ng/mL) than ASD (180.5±75.1 ng/mL) and APC (549.7±113.5 ng/mL). Compared with ASD, 1 and 2 were both remarkably shortened by APC-SNEDDS. The oral bioavailability in rats was enhanced significantly to 183.8% and 431.8% by APC and APC-SNEDDS, respectively.
CONCLUSION: These results indicated that APC-SNEDDS was a promising drug delivery system to enhance the oral bioavailability of ASD.

Keywords

Akebia saponin D oral bioavailability phospholipid complex self-nanoemulsifying drug delivery systems

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MeSH Term

Administration, Oral
Animals
Biological Availability
Calorimetry, Differential Scanning
Drug Delivery Systems
Emulsions
Ethylene Glycols
Female
Glycerides
Male
Particle Size
Phospholipids
Polyethylene Glycols
Rats, Sprague-Dawley
Saponins
Solubility
Spectroscopy, Fourier Transform Infrared
Surface-Active Agents

Chemicals

Emulsions
Ethylene Glycols
Glycerides
Phospholipids
Saponins
Surface-Active Agents
akebia saponin D
cremophor
Polyethylene Glycols
carbitol
monoolein
Journal Article
Article has an altmetric score of 1

Word Cloud

Created with Highcharts 10.0.0ASDAPCoralAPC-SNEDDSbioavailabilityng/mLdrugdeliverycomplexAkebiasaponinself-nanoemulsifyingsystemformulationsignificantlyoil12DSNEDDSbasedcharacterizedmorphologyobservationsolubilitytestcosurfactantselectedsurfactantoptimizedsizedeterminationzetapotentialdilutionstabilityratsGlycerylmonooleatePolyoxyl35castorDiethyleneglycolmonoethyletherrespectivelyshowedgreater8%BACKGROUND:exertsvariouspharmacologicalactivitiespoorstudydrug-phospholipidtechniquedevelopedimproveabsorptionMETHODS:ASD-phospholipidpreparedusingsolvent-evaporationmethodinfraredspectroscopydifferentialscanningcalorimetryOilaccordingabilitydissolvechosenemulsificationefficiencyPseudoternaryphasediagramsconstructeddeterminedropletRobustnessthermodynamicalsoevaluatedSubsequentlypharmacokineticparametersinvestigatedRESULTS:liposolubilityincreased114-foldformationverified-octanolPeceol[type40]CremophorELTranscutolHPoptimalcomposedtype401:45:45:174w/w/w/wparticle1480±27nm-137±092mVdistilledwaterratio1:100w/wgoodcolloidalPharmacokineticstudiesexhibited7334±20384372±1749858±36661805±755497±1135Comparedremarkablyshortenedenhanced183431CONCLUSION:resultsindicatedpromisingenhancePreparationevaluationloadedD-phospholipidphospholipidsystems

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