Preparation and Characterization of Nanoparticles Shelled with Chitosan for Oral Insulin Delivery

Abstract

Nanoparticles (NPs) composed of chitosan (CS) and poly(γ-glutamic acid) (γ-PGA) were prepared by a simple ionic-gelation method for oral insulin delivery. Fourier transform infrared (FT-IR) spectra indicated that CS and γ-PGA were ionized at pH 2.5-6.6, while X-ray diffractograms demonstrated that the crystal structure of CS was disrupted after it was combined with γ-PGA. The diameters of the prepared NPs were in the range of 110-150 nm with a negative or positive surface charge, depending on the relative concentrations of CS to γ-PGA used. The NPs with a positive surface charge (or shelled with CS) could transiently open the tight junctions between Caco-2 cells and thus increased the paracellular permeability. After loading of insulin, the NPs remained spherical and the insulin release profiles were significantly affected by their stability in distinct pH environments. The in vivo results clearly indicated that the insulin-loaded NPs could effectively reduce the blood glucose level in a diabetic rat model.

Chitosan nanoparticles: a survey of preparation methods

“…2008b), cyclodextrins (Teijeiro-Osorio et al 2009), poly-γ-glutamic acid (Lin et al 2007, Lin et al 2008) and poly(acrylic acid) (Hu et al 2002), as well as protein-based molecules, like insulin (Bayat et al 2008), or even DNA (Erbacher et al 1998, Xu et al 2011. One work reports the use of sodium lauryl sulfate (Elsayed et al 2011).…”

“…Chitosan, alginate, arabic gum, carboxymethyl cellulose, carrageenan, chondroitin sulfate, cyclodextrins, dextran sulfate, polyacrylic acid, poly-γ-glutamic acid, insulin, DNA (Erbacher et al 1998, Hu et al 2002, Du et al 2004, Sarmento et al 2006a, Sarmento et al 2006b, Lin et al 2007, Bayat et al 2008, Lin et al 2008, Teijeiro-Osorio et al 2009, Avadi et al 2010, Grenha et al 2010b, Kaihara et al 2011, Yeh et al 2011 Modified ionic gelation with radical polymerisation Chitosan, acrylic acid, methacrylic acid, polyethylene glycol, polyether (Hu et al 2002, Sajeesh and Sharma 2006a, Sajeesh and Sharma 2006b Desolvation Chitosan (Mao et al 2001, Borges et al 2005 Targeting 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 ...…”

Influence of magnesium stearate on the physicochemical and pharmacodynamic characteristics of insulin-loaded Eudragit entrapped mucoadhesive microspheres

“…Figure 4 also shows a slight reduction in blood glucose level after oral administration of insulin solution. It is quite improbable for insulin absorption to occur in the stomach (Chandler et al, 1994;Damage et al, 1995;Sarciaux et al, 1995;Iwanaga et al, 1997;Krauland et al, 2004;Li & Deng, 2004;Nakamura et al, 2004;Sajeesh & Sharma, 2006;Lin, 2007); thus the reduction in the blood glucose could be due to some of the insulin solution reaching the intestine since high doses of insulin solution were administered to the rats. Blood glucose reduction occurred within 30 min of oral administration in some samples.…”

“…The oral route is considered to be the most convenient, acceptable and desired route of drug delivery which will help eliminate the pain caused by injection, psychological barrier associated with multiple daily injection and possible infections (Kisel et al, 2001;Kim & Peppas, 2003;Whitehead et al, 2004;Cui et al, 2006;Sarmento et al, 2007). Oral delivery of insulin as a non-invasive therapy for diabetes mellitus is still a challenge to the drug delivery technology, due to low oral bioavailability, lack of lipophility, poor permeability across intestinal epithelium because of insulin high molecular weight as well as digestion by proteolytic enzymes in the luminal cavity (Tozaki, 2001; Gowthamarajan & Kulkarni, 2003;Tiyaboonchai, 2003;Krauland et al, 2004;Li & Deng, 2004;Nakamura et al, 2004;Toorisaka et al, 2005;Sajeesh & Sharma, 2006;Sarmento, 2006;Tuesca & Lowman, 2006;Lin, 2007;Simon, 2007).…”

Oral Delivery of Insulin: Novel Approaches

“…This might be related to the fact that both insulin and chitosan have net positive charges at pH 1.2, that the columbic repulsive forces lead to the dissociation of the complex and that the free insulin is subjected to degradation. For example, nanoparticles prepared from chitosan and poly ( -glutamic acid) became unstable at pH 1.2 and broke apart [93] and nanoparticles composed of chitosan and tripolyphosphate rendered the protein more susceptible to acid and enzymatic hydrolysis [94]. In the present investigation, we benefited from the advantages of polyelectrolyte complexation between chitosan and insulin, its formulation in an aqueous environment without the need for heat or an organic solvent, and the solution of the shortcomings of burst release by the dispersion of nanoparticles in an oily phase.…”