Nasal polysaccharides-glucose regulator microparticles: Optimization, tolerability and antidiabetic activity in rats

• Repaglinide was efficiently incorporated in microparticles made of anionic polysaccharides.
• A 32 factorial design was set to study formulation effects on drug release.
• Prepared systems were well tolerated on nasal tissues and suitable for nasal administration.
• Anionic polysaccharides did not have any diabetogenic effect on the rats.
• Tailored drug antidiabetic effect related to release, mucoadhesive and swelling was achieved.

The aim of the present study was to load the post-prandial glucose regulator, repaglinide (REP), on spray dried mucoadhesive microparticles (MPs) comprising anionic polysaccharides. The formulation parameters of the polysaccharides-REP spray dried powders (SDP) namely, polysaccharide type and drug to polymer (D/P) ratio, were optimized for % release after 5 min (R%5 min) and time required for 80% release (T80%). The suitability of the selected formulae for nasal application was evaluated by ex vivo mucoadhesion, in vitro cytocompatability and tolerability studies. A pharmacodynamic study in diabetic rats was conducted. Results showed that both polysaccharide type and amount greatly influenced the chosen responses. REP was highly incorporated in mucoadhesive MPs with proven safety on the rat nasal mucosa. The selected REP loaded powders exhibited a significant two to threefold increase in total decrease in blood glucose compared to the nasal and intravenous solutions.