No abstract

Specific, efficient and targeted delivery of siRNAs is the major concern for their in vivo administrations. Also, anatomical barriers, drug stability and availability, immunoreactivity and existence of various delivery routes, different genetic backgrounds are major clinical challenges. However, successful administration of siRNA-based drugs is expected during foreseeable features. But, their systemic applications will depend on strong targeted drug delivery strategies.

No abstract

Abstract1,2-Distigmasterylhemisuccinoyl-sn-glycero-3-phosphocholine (DSHemsPC) is a new lipid in which two molecules of stigmasterol (an inexpensive plant sterol) are covalently linked via a succinic acid to glycerophosphocholine. Since amphotericin B (AmB) interacts with sterols, we postulated that DSHemsPC could be used in AmB liposome formulations. Thirty-two DSHemsPC-AmB formulations were prepared using various mole ratios of DSHemsPC, phosphatidylcholine and phosphatidylglycerol at different pH. Most formulations had physical properties similar to AmBisome™: a particle diameter of about 100 nm, a monomodal distribution and a negative zeta potential. The red blood cell potassium release (RBCPR) IC50s for formulations spanned a range, with some being comparable to or greater than the IC50 observed using AmBisome™. A number of formulations had superior in vitro antifungal activity compared to AmBisome™. against all of the tested pathogenic yeasts and molds. The IC50s of formulations against L. major promastigotes and amastigotes for certain formulations were comparable with AmBisome™ and Fungizone™. Most formulations had maximum tolerated intravenous doses (MTD) of less than 10 mg/kg. However the formulation consisting of DSHemsPC/DMPC/DMPG/ AmB mole ratio 1.25/5.0/1.5/1.0 (prepared at pH 5.5) had excellent colloidal properties, a high IC50 for RBCPR, antifungal and antileishmanial activity similar to AmBisome™ and an MTD of 60 mg/kg. The characteristics of this DSHemsPC/DMPC/DMPG/AmB formulation make it suitable for further investigation to treat AmB-responsive pathogens.