Design of self-polymerized insulin loaded poly(n-butylcyanoacrylate) nanoparticles for tunable oral delivery.

Macromolecular drugs, characterized by low stability and large molecular weight, still faced various difficulties by oral administration. And controlling drugs' release rate to reach the physiological concentration in the blood was recognized as one of the main challenges in this field but no studies are available so far. Thus, the objective of this study was to investigate the effect of insulin release rate on its in vitro and in vivo behavior when other obstacles (drug stability, mucus penetration and retention in gastrointestinal tract) was firstly overcome. Using n-butylcyanoacrylate (BCA) as the carrier, insulin-loaded Poly (n-butylcyanoacrylate) nanoparticles (Ins/PBCA NPs) were prepared by self-polymerization and the release rate of insulin was controlled by adjusting the mass ratio of Insulin/BCA. The NPs exhibited good stability in gastric fluid with controlled release in intestine and the release rate increased with the increase of Insulin/BCA mass ratio. All the Ins/PBCA NPs with different release rate showed excellent mucus penetration (>60%, 10 min) and strong gastrointestinal retention (~70%, 12 h). Especially, all the NPs showed promising hypoglycemic effect with the extent depending on drug release rate. Ins/BCA = 2/10 NPs exhibited fast hypoglycemic effect, while Ins/BCA = 2/15 NPs showed slow and outstanding performance. In conclusion, Ins/PBCA NPs could not only overcome the oral barriers of insulin delivery but also provide desired hypoglycemic effect by controlling insulin release rate.