Polysaccharide coated niosomes for oral drug delivery: formulation and in vitro stability studies

Non-ionic surfactant vesicles (niosomes) were prepared and appended with a polysaccharide cap using hydrophobic anchors. Hydrophobized polysaccharides, O-palmitoyl pullulan (OPPu) and cholesteroyl pullulan (CHPu) were anchored onto propranolol.HCL containing preformed niosomes. The coated niosomes were characterized for average vesicle size, size distribution, shape, encapsulation efficiency and in vitro release profile and were compared with their uncoated counterparts. No significant difference was observed in % encapsulation (P > 0.05 in a rank sum test) of polysaccharide coated and uncoated vesicles. In vitro release studies however, revealed a significant lowering (P < 0.01) of drug release for the coated systems in simulated gastric and intestinal fluids with a biphasic release profile. The influence of the hydrophobized polysaccharide cap on niosomal membrane integrity and stabilization against harsh bio-environment conditions was also investigated. The parameters investigated include detergent and bile (bile salts and fresh-pooled rat bile) challenge, freeze-thaw cycling, osmotic stress, and long term and shelf stability studies. It was seen that at higher bile salt concentrations and detergent content, uncoated niosomes underwent bilayer solubilization into intermediate micellar structures, whereas coated niosomes were able to maintain their structural integrity as reflected from their higher % latency for the entrapped water soluble agent. Similarly, freeze-thaw cycling could not bring any fusion or collapse of the niosomal membrane (unlike uncoated ones). Furthermore, the exceptional shelf stability of the coated vesicles both at 37 +/- 1 degrees and at 4 +/- 1 degrees C establishes the potential of polysaccharide coated niosomes as an oral delivery system for water-soluble agents. Results from OPPu and CHPu coated niosomal systems for their oral stability potential are compared.