Background: Targeted drug delivery to colon would ensure direct treatment at the disease site, decrease in dose administration and reduction side effects improved drug utilization. Objective: The purpose of this research was to decrease gastric side effects of piroxicam by formulating microspheres of alginate and algino-pectinate beads of the drug. Materials and Methods: Ionotropic gelation was used to entrap piroxicam into alginate and algino-pectinate mucoadhesive microspheres as a potential drug carrier for oral delivery of piroxicam. Microparticles with different drug to polymers ratio were prepared and characterized by encapsulation efficiency, particle size, DSC (differential scanning calorimetric), mucoadhesive property, gastroretentive time and drug release studies. Results:The best drug to polymer ratio of microparticles was 1:2.5 (F 1 ) with Na-Alg and 1:7.5 (F 4 ) with Alg-Na with pectin, respectively. The microparticles F 1 and F 4 showed 28.80%, 50.01% loading efficiency, 82.57%, 82.31% production yield and 945.4, 899.91 µm mean particle size. DSC showed stable character of piroxicam in drug-loaded microparticles and revealed amorphous form. It was found that microparticles (Na-Alg) prepared had faster release and microparticles (Alg-Na and pectin mixture) prepared had slower release than untreated piroxicam (P < 0.05). Microparticles (mixture of Na-Alg and pectin) exhibited very good percentage of mucoadhesion and flowability properties. Mucoadhesion strength and retention time study showed better retention of piroxicam microparticles in intestine. Besides, there was a significant higher retention of mucoadhesive microparticles in upper GI tract. Conclusions: Algino-pectinate mucoadhesive formulations exhibited promising properties of a sustained release form for piroxicam and provided distinct tissue protection in stomach. BackgroundIn general, rapid absorption from mucous routes is observed because of thin mucus membrane and rich blood supply. After absorption, drug is transferred by the deep lingual vein or facial vein and then drains into the general circulation via the jugular vein, bypassing the liver and thereby sparing the drug from first-pass metabolism. The term 'mucoadhesive' describes materials that bind to biological substrate, such as mucosal membranes. Adhesion of mucoadhesive drug delivery devices to mucosal membranes increases drug concentration gradient at the absorption site and therefore improves the bioavailability of systemically delivered drug (1). Polysaccharides polymers such as alginates have been investigated in the last years as carrier for controlled drug release (2, 3), cell encapsulation (4), tissue engineering material (5), or taste masking in pediatric formulations (6). Encapsulation property of alginate is due to its ability to move from sol to gel state by ionotropic gelation under mild conditions through interactions with bivalent or trivalent cations (7). The resulting particles are able to protect drugs from environmental stress or, based on alginate pH depend...