Chitosan-modified cholesterol-free liposomes for improving the oral bioavailability of progesterone.

Based on the structurally similar properties of progesterone and cholesterol, chitosan-coated cholesterol-free liposomes (CS-Lipo/Prog) were formulated. CS-Lipo/Prog are spherical and uniform in size (662.1±19.3nm) with positive potential (28.19±1.97mV). The average drug entrapment efficiency (EE) is approximately 80%. The in vitro release profile of CS-Lipo/Prog shows sustained release. The in vitro stability evaluation demonstrated that CS-Lipo/Prog can efficiently shield Prog from degradation in the gastrointestinal tract. CS-Lipo/Prog showed a longer MRT and higher AUC0-infinite after oral administration to mice than in the control group (progesterone-free). The relative bioavailability of CS-Lipo/Prog was higher than that of progesterone soft capsules (QINING®) and Lipo/Prog. Collectively, these findings suggest that cholesterol-free chitosan-coated liposomes are a promising alternative for improving the oral bioavailability of progesterone.

[1]  Guihua Huang,et al.  Chitosan coated vancomycin hydrochloride liposomes: Characterizations and evaluation. , 2015, International journal of pharmaceutics.

[2]  C. Charcosset,et al.  Effect of Progesterone, Its Hydroxylated and Methylated Derivatives, and Dydrogesterone on Lipid Bilayer Membranes , 2015, The Journal of Membrane Biology.

[3]  G. Betageri,et al.  Mixed-Micellar Proliposomal Systems for Enhanced Oral Delivery of Progesterone , 2006, Drug delivery.

[4]  Ji-Ho Park,et al.  Liposomal delivery systems for intestinal lymphatic drug transport , 2016, Biomaterials Research.

[5]  H. Takeuchi,et al.  N-trimethyl chitosan-modified liposomes as carriers for oral delivery of salmon calcitonin , 2011, Drug delivery.

[6]  Ramon Pons,et al.  Physico-chemical characterization of succinyl chitosan-stabilized liposomes for the oral co-delivery of quercetin and resveratrol. , 2017, Carbohydrate polymers.

[7]  F. Bounoure,et al.  Solubility and Dissolution Rate of Progesterone-Cyclodextrin-Polymer Systems , 2006, Drug development and industrial pharmacy.

[8]  Zhuxian Zhou,et al.  Amphiphilic drugs as surfactants to fabricate excipient-free stable nanodispersions of hydrophobic drugs for cancer chemotherapy. , 2015, Journal of controlled release : official journal of the Controlled Release Society.

[9]  Balram Sahu,et al.  Development of a Liposome Based Contraceptive System for Intravaginal Administration of Progesterone , 1997 .

[10]  S. Bharate,et al.  Incompatibilities of Pharmaceutical Excipients with Active Pharmaceutical Ingredients: A Comprehensive Review , 2010 .

[11]  Y. Darwis,et al.  Advanced drug delivery to the lymphatic system: lipid-based nanoformulations , 2013, International journal of nanomedicine.

[12]  A. Healy,et al.  Characterisation of excipient-free nanoporous microparticles (NPMPs) of bendroflumethiazide. , 2008, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[13]  Hirofumi Takeuchi,et al.  Novel mucoadhesion tests for polymers and polymer-coated particles to design optimal mucoadhesive drug delivery systems. , 2005, Advanced drug delivery reviews.

[14]  Wei Wu,et al.  Enhanced oral absorption of insulin-loaded liposomes containing bile salts: a mechanistic study. , 2014, International journal of pharmaceutics.

[15]  Mei Wang,et al.  A New Type of Liquid Silymarin Proliposome Containing Bile Salts: Its Preparation and Improved Hepatoprotective Effects , 2015, PLoS ONE.

[16]  Xin Wang,et al.  The potential use of novel chitosan-coated deformable liposomes in an ocular drug delivery system. , 2016, Colloids and surfaces. B, Biointerfaces.

[17]  B. Sarmento,et al.  Facilitated nanoscale delivery of insulin across intestinal membrane models. , 2011, International journal of pharmaceutics.

[18]  M. Al-Asmakh.  Reproductive functions of progesterone , 2008 .

[19]  Liu Liu,et al.  Progesterone Enhances Immunoregulatory Activity of Human Mesenchymal Stem Cells Via PGE2 and IL‐6 , 2012, American journal of reproductive immunology.

[20]  Wei Wu,et al.  Oral delivery of liposomes. , 2015, Therapeutic delivery.

[21]  M. Bally,et al.  Improved retention of idarubicin after intravenous injection obtained for cholesterol-free liposomes. , 2002, Biochimica et biophysica acta.

[22]  Hefeng Huang,et al.  miR-155 mediates suppressive effect of progesterone on TLR3, TLR4-triggered immune response. , 2012, Immunology letters.

[23]  Yanan Tan,et al.  Hypoglycemic activity and oral bioavailability of insulin-loaded liposomes containing bile salts in rats: the effect of cholate type, particle size and administered dose. , 2012, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[24]  J. Thompson,et al.  A study of the interaction between progesterone and membrane lipids. , 1983, Endocrinology.

[25]  Zhenhai Zhang,et al.  Improved oral bioavailability and anticancer efficacy on breast cancer of paclitaxel via Novel Soluplus(®)-Solutol(®) HS15 binary mixed micelles system. , 2016, International journal of pharmaceutics.

[26]  S. Yamashita,et al.  Application of surface-coated liposomes for oral delivery of peptide: effects of coating the liposome's surface on the GI transit of insulin. , 1999, Journal of pharmaceutical sciences.