Nasal delivery protects drugs like salbutamol sulphate (SS) from hepatic first-pass metabolism. The study aimed to formulate mucoadhesive sodium alginate (SA) microspheres loaded with (SS) by emulsion cross-linking, with mucoadhesive polymers, for potential nasal delivery by-passing first-pass metabolism. Relevant physichochemical properties, in vitro release and irritation in rabbits were investigated. Stirring rate and cross-linking time affected microsphere parameters. Microspheres were spherical in shape, discrete, with smooth and porous properties favorable for intranasal absorption with high drug-loading of 78.7 %. Mixed-polymers microspheres exhibited higher degree of swelling. Kinetic analysis of release data showed a case II release kinetics for alginate microspheres, and anomalous mechanism for other mixed-polymers formulae. Pronounced sustained drug release over 8 hours was exhibited upon incorporation of Carbopol® 934 and Hydroxypropyl methyl cellulose. The formulated microspheres showed high swelling ability and good mucoadhesion, offering a good potential for future in vivo study to confirm safety and avoidance of first-pass metabolism.