| Summary: | Diabetes mellitus is a chronic metabolic condition, which is characterised by high blood
glucose level due to defect in insulin producing cells. The current diabetes therapy is
subcutaneous insulin injections. However, frequent daily injections may lead to low
patient compliance and substantial inconvenience. Several alternative routes of insulin
delivery are being investigated including oral, pulmonary, nasal, buccal and inhaled
routes. Although the oral route is the most convenient way of drug delivery, insulin is
vulnerable to rapid degradation in the stomach and low intestinal permeation. The
polymeric nanocarriers have recently attracted considerable attention as oral delivery
vehicles for insulin. These nanocarriers may protect insulin from degradation and
facilitate insulin absorption through transcellular and/or paracellular route. This project
aimed to fabricate cationic ~-cyclodextrin (C~CD)-insulin-Ioaded alginate
nanoparticles and evaluate their potential as oral insulin delivery system. C~CD were
prepared from ~-cyclodextrin (~-CD) through a one-step polycondensation by utilizing
choline chloride (CC) to provide ammonium group and epichlorohydrin (EP) to form
polymeric chains. The synthesised C~CD was confirmed through nuclear magnetic
resonance (NMR) spectroscopy. Afterwards, insulin was complexed with C~CD via
both inclusion and electrostatic attraction with the aim of enhancing the insulin release
profile. This complex was investigated using Fourier transform infrared (FT-IR) and
then encapsulated into calcium alginate nanoparticles by two-step procedure based on
ionic gelation method. The size, polydispersity index (PDI), zeta potential,
encapsulation efficiency (EE), surface morphology and cumulative drug release of the
nanoparticles were estimated using different characterization techniques such as;
Dynamic light scattering (DLS), transmission electron microscopy (TEM) and
ultraviolet-visible (UV - Vis) spectrophotometry. In vitro cytotoxicity activity of the
nanoparticies against HT -29 cells were evaluated by 3-( 4,5-dimethylthiazol-2-yl)-2,5-
diphenyl-2H-tetrazolium bromide (MTT) assay using different nanoparticles
concentrations. C~CD-insulin-Ioaded alginate nanoparticles were characterized by
reduced particle size as well as improved encapsulation efficiency and minimal insulin
release into simulated gastric fluid (SOF) as a result of the strong electrostatic attraction
between insulin and C~CD. The optimised nanoparticle formulation exhibited particle
size at 339.53 ± 20.88 nm, encapsulation efficiency at 81.88 ± 1.72 % and cumulative
insulin release in (SOF) at 9.36 ± 0.49 % compared with 445.4 ± 152.94 nm, 45.65 ±
1.49 % and 49.69 ± 1.75 % of that without C~CD, respectively. MTT assay revealed
that all formulations were considered non-toxic toward HT -29 cells. The present study
advocated that C~CD-insulin-Ioaded alginate nanoparticles can be a promising system
for enhancing insulin oral delivery.
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