Preparation, Characterization and In Vivo Studies of Proliposomes Containing Cyclosporine A

Abstract

The present study was undertaken to prepare proliposomes of Cyclosporine A (CsA) to increase its oral bioavailability. The proliposomes were prepared by spraying a solution of CsA, egg lecithin and cremophor EL in methanol-chloroform mixture onto directly compressible lactose (carrier) in a rotary evaporator. A dry free flowing powder of proliposomes was obtained. The dry proliposomal powder was characterized for surface morphology by scanning electron microscopy (SEM). Then the proliposomes were hydrated with distilled water to produce liposomes, which were characterized for particle size distribution, % drug entrapment, and morphological characteristics by transmission electron microscopy (TEM). The liposomes exhibited good entrapment of about 99%. The entrapment of CsA in liposomes was found to be dependent mainly on the drug:lipid ratio. Bioavailability studies were carried out for three different formulations of CsA i.e., free drug suspension; proliposomes derived liposomes and marketed formulation (Pannimun Bioral, Microemulsion) on male SD rats. The results of bioavailability studies indicated that the difference in the mean drug concentration of the free drug and the liposomes was found to be statistically significant (p < 0.05, p value is 0.032). The absorption constant for liposomal product was much greater (10.26 h(-1)) than for free drug solution (1.2 h(-1)) or the marketed sample of microemulsion (2.51 h(-1)) and the volume of distribution was found to be less for liposomes (7629.88 ml/kg) than that of the free drug solution (10971.92 ml/kg) and marketed microemulsion (9012.07 ml/kg). The results of these studies have shown that a stable proliposomal formulation of CsA for oral administration can be prepared which can be easily hydrated into liposomes from which CsA can exert its clinical effects with a better oral bioavailability.

Preparation and evaluation of cyclosporin A-containing proliposomes: a comparison of&nbsp;the supercritical antisolvent process with the conventional film method

“…The thin film hydration method 19,20 was adopted as the conventional method used to prepare proliposomes for comparison with proliposomes containing CsA that were prepared by a novel SAS process. Phospholipids, cholesterol, and CsA were dissolved in organic solvents, followed by sonication (Ultrasonic Cleaner UC-20; Jeio Tech Co., Ltd., Seoul, Republic of Korea) until a clear and homogeneous solution was obtained.…”

Immunosuppressive and Anti-Inflammatory Properties of Engineered Nanomaterials

“…Cyclosporine Liposomes (Freise et al, 1994;Shah et al, 2006); polymeric NP (Gref et al, 2001;Italia et al, 2007;Azzi et al, 2010;Tang et al, 2012); lipid NP (Muller et al, 2008) Preclinical Tacrolimus Lipid NP (Pople and Singh, 2012); polymeric NP (Tammam et al, 2012); liposomes (Erdogan et al, 2002;Zhang et al, 2010) Preclinical Rapamycin/sirolimus Polymeric NP (Yuan et al, 2008;Woo et al, 2012;Shah et al, 2013); micelles (Yanez et al, 2008;Chen et al, 2013); liposomes (Rouf et al, 2009;Ghanbarzadeh et al, 2013) Preclinical Mycophenolic acid Polymeric NP (Shirali et al, 2011); nanogels (Look et al, 2013); dendrimers (Hu et al, 2009) Preclinical Corticosteroids Liposomes Linker et al, 2008;Schweingruber et al, 2011;Ulmansky et al, 2012); polymeric NP (Ishihara et al, 2005;Matsuo et al, 2009); solid lipid NP (Jensen et al, 2010;Zhang and Smith, 2011); dendrimers (Khandare et al, 2005) Preclinical Non-steroidal anti-inflammatory Dendrimers (Chauhan et al, 2004;Na et al, 2006;Chandrasekar et al, 2007;Cheng et al, 2007); nanocolloid (Milkova et al, 2013); lipid NP (Castelli et al, 2005); liposomes (Paavola et al, 2000;Srinath et al, 2000;Turker et al, 2008)…”

Oral cyclosporine A - the current picture of its liposomal and other delivery systems

“…Liposomal CsA was reported to be preferably absorbed by Peyer's patches following oral administration [53]. It was shown that such formulations may exhibit both bioequivalence with microemulsions [54,55] and diminished inter-individual variations in bioavailability [56]. The problem of the poor shelf-life stability of liposomal CsA formulations can be overcome via the preparation of a dry proliposome powder [55].…”

“…It was shown that such formulations may exhibit both bioequivalence with microemulsions [54,55] and diminished inter-individual variations in bioavailability [56]. The problem of the poor shelf-life stability of liposomal CsA formulations can be overcome via the preparation of a dry proliposome powder [55]. Cyclodextrins Improved bioavailability, reduced variability in absorption [80,81] Prodrugs High solubility in water, unknown pharmacokinetics [21,22] Brought to you by | MIT Libraries Authenticated Download Date | 5/12/18 5:24 AM Micelles composed of modified polysaccharides [64] are one of the promising alternative oral delivery vehicles.…”