Development of Sustained Release Nateglinide Loaded PLGA Nanoparticle: In vitro-In vivo Study

Gite Sandip¹, Sav Ajay Kumar^2*, Khose, Yogesh³, Jain Shailesh³

1.Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N. P. Marg, Matunga, Mumbai- 400019, India

2.Macleods Pharmaceuticals Ltd., Andheri East, Mumbai-400093, India

3. VNS Group of Educational Institutes (Corporate Office), MP Nagar, Bhopal – 462011, India.

ABSTRACT

In present study long-acting biodegradable Nateglinide loaded Poly (lactic-co-glycolic) acid nanoparticleformulation is reported for treatment of Type 2 Diabetes Mellitus (T2DM).Different formulations were prepared by varying drug: polymer ratio (1:1, 1:2, and 1:3) and polyvinyl alcohol as stabilizer in 0.5-1.5% concentration range by emulsificationsolventevaporation technique. Optimization was carried out by evaluating entrapment efficiency and particle size. Optimized formulation was characterized for in vitro drug release, surface charge property, SEM, chemical incompatibility and invivo evaluated for blood glucose lowering property in rat model. The obtained resultsindicatethat formulation composition containing drug:polymer ratio 1:3 and stabilizer concentration 1.5%  gives high encapsulation efficiency (82.15%) with mean particle diameter of 216 nm and drug release for 72h. Drug release data was best fitted to Higuchi model indicating drug release was mainly took place by diffusion mechanism. Oraladministrationof optimized nanoparticle formulation showed two fold better activity as compared to standardNateglinide formulation(P<0.05). Study suggested that Nateglinide loaded controlled PLGA nanoparticle can be used for better control of blood glucose level by sustaining its release. 

Keywords:Nateglinide, PLGA, Poly vinyl alcohol, nanoparticle, Diabetes mellitus