Alginate–C18 Conjugate Nanoparticles Loaded in Tripolyphosphate-Cross-Linked Chitosan–Oleic Acid Conjugate-Coated Calcium Alginate Beads as Oral Insulin Carrier

Abstract

Simple alginate, alginate-stearic acid, and alginate-C18 conjugate nanoparticles and tripolyphosphate-cross-linked chitosan-oleic acid conjugate-coated calcium alginate beads as the vehicle of nanoparticles were designed. Their size, ζ potential, morphology, drug load, drug release, matrix molecular characteristics, mucus penetration, HT-29 cell line cytotoxicity and intracellular trafficking, in vivo blood glucose lowering, and insulin delivery profiles were characterized. Alginate-C18 conjugate nanoparticles were nontoxic. Among all nanoparticle variants, they had reduced size and ζ potential thus enhancing particulate mucus penetration and intracellular trafficking. Their insulin reabsorption tendency was minimized as alginate active COOH/COO- sites were preoccupied with C18. Their loading into coated beads was translated to reduced drug release in simulated gastric phase with nanoparticles being released in the intestinal phase. The combination dosage form increased the blood glucose lowering extent of insulin and blood insulin level compared with nanoparticles or beads alone. Nanoparticles in beads represented a viable approach for oral insulin delivery.

Development of orally administered insulin-loaded polymeric-oligonucleotide nanoparticles: statistical optimization and physicochemical characterization

“…For instance, the lyophilized insulin-loaded modified chitosan nanoparticles did not show any toxicity in GI cells after being treated for 3 h [8]. For the pharmaceutical development of insulin-loaded nanoparticles, HT29 cells [101] and C2C12 cells [102,103] control, Analysis of Variance revealed that all tested samples introduced negligible cytotoxicity to the C2C12 cells. Therefore, the fabricated nanoparticles and excipients in the formulation were biocompatible and safe at the tested concentration.…”

Alginate Nanoformulation: Influence of Process and Selected Variables

“…The processing parameters used were as follows: air flow rate 2–2.5 m/s, solution feed rate 4 mL/min and atomizing air pressure 6 bar. The inlet temperature and outlet temperature were 60 °C and 23 °C, respectively [ 57 ]. Shehata and Ibrahima, on the other hand, have encapsulated metformin hydrochloride into nanoparticles consisting of alginate/gelatin with 1:3 ratio using nano-spray dryer.…”

“…Alginate-based nanocarrier seems to have all optimal requirements to be a successful drug delivery system due to its biodegradability, biocompatibility, protection effect of oral drugs against harsh gastrointestinal environment, controllable release, water solubility (avoiding the effect of noxious solvents during processing), availability and low cost [ 55 ]. Various studies have focused on enhancing the low intestinal penetration, gastrointestinal degradation and low bioavailability of orally administered insulin utilizing alginate nanoparticles as an oral drug delivery system [ 56 , 57 ]. On top of that, the application of alginate nanoparticles in cancer treatment has gained wide attention due to the ability to deliver anti-cancer therapeutics in sufficient manner at target site, promoting the bioavailability as well as reducing drug dosage and its side effects to the normal tissues [ 58 , 59 ].…”

Design and Investigation of Alginate Coated Solid Lipid Nanoparticles for Oral Insulin Delivery

“…20 A variety of alginate carriers ranging from beads to micro and nanoparticles for the oral delivery of insulin have been investigated for sustained release while protecting the drug from enzymatic degradation. [21][22][23] But, such approaches resulted in low encapsulation efficiency due to the rapid release of hydrophilic insulin into the cross linking medium. To counteract this problem, many studies reported the use of the formation of polyelectrolyte complex between chitosan and alginate with β-cyclodextrin for entrapping the drug.…”