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

Abstract

Introduction: Therapeutic peptides are administered via parenteral route due to poor absorption in the gastrointestinal (GI) tract, instability in gastric acid and GI enzymes. Polymeric drug delivery systems have achieved significant interest in pharmaceutical research due to its feasibility in protecting proteins, tissue targeting and controlled drug release pattern. Materials and Methods:In the present study, the size, polydispersity index and zeta potential of insulin-loaded nanoparticles were characterized by dynamic light scattering and laser doppler micro-electrophoresis. The main and interaction effects of chitosan concentration and Dz13Scr concentration on the physicochemical properties of the prepared insulin-loaded nanoparticles (size, polydispersity index and zeta potential) were evaluated statistically using Analysis of Variance. A robust procedure of reversed-phase high-performance liquid chromatography was developed to quantify insulin release in simulated GI buffer. Results and Discussion:We reported on the effect of two independent parameters, including polymer concentration and oligonucleotide concentration, on the physical characteristics of particles.Chitosan concentration was significant in predicting the size of insulin-loaded CS-Dz13Scr particles.In terms of zeta potential, both chitosan concentration and squared term of chitosan were significant factors that affect the surface charge of particles, which was attributed to the availability of positively-charged amino groups during interaction with negatively-charged Dz13Scr. The excipients used in this study could fabricate nanoparticles with negligible toxicity in GI cells and skeletal muscle cells. The developed formulation could conserve the physicochemical properties after being stored for 1 month at 4 o C. Conclusion:The obtained results revealed satisfactory results for insulin-loaded CS-Dz13Scr nanoparticles (159.3 nm, pdi 0.331, -1.08 mV). No such similar study has been reported to date to identify the main and interactive significance of the above parameters for the characterization of insulin-loaded polymeric-oligonucleotide nanoparticles. This research is of importance for the understanding and development of protein-loaded nanoparticles for oral delivery.

Chitosan Nanoparticles in Atherosclerosis—Development to Preclinical Testing

“…As chitosan has various beneficial effects on human health, for instance, in bone healing [ 48 , 49 ], it makes it quite an ideal biomaterial to employ in the drug delivery research sector. Various labs, including ours [ 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 ], have shown that chitosan is capable of encapsulating various types of therapeutic agents such as small molecule drugs to exploratory biologicals such as proteins and even DNA in delivery platforms of various sizes. As chitosan can even be ingested with no complications, this fact further cements the usefulness of this biopolymer in drug delivery R&D. Chitosan NPs have been formulated in the past using various methods, not limited to complex coacervation [ 64 ] and ionotropic gelation [ 65 ], both simple enough to carry out in most labs.…”

“…HGC NPs are biodegradable, have low immunogenicity and are adaptable to carry a variety of therapeutic agents in vivo [ 69 , 70 ]. Depending on the formulation technique used, this biopolymer can be relatively inexpensive and easy to use, as we [ 60 , 61 , 62 , 71 , 72 , 73 ] and others [ 74 , 75 ] have established previously. We now review the collection of articles in the literature that have used chitosan-based NPs in atherosclerosis research (none has yet been tested clinically, so the discussions revolve around cell culture and preclinical animal models testing)—that is, tested as a diagnostic, therapeutic or both diagnostic and therapeutic (theranostic) platform.…”

C2C12 cell model: its role in understanding of insulin resistance at the molecular level and pharmaceutical development at the preclinical stage

“…[43,205,216,217] Nanoparticles possess several favourable properties, including stability against enzymatic degradation, improved bioavailability and high carrier capacity. [218][219][220][221] One of the studies examined the antidiabetic effects of bioflavonoids-loaded nanoparticles on C2C12 cells and streptozotocin-induced diabetic rat model. [121] It was found that nanoparticles containing myricitrin (1, 3, and 10 mg/kg) could increase glycogen synthesis and its storage, GLUT-4 gene expression, glucose uptake and cell viability in C2C12 cells.…”

Oligonucleotide Therapies in the Treatment of Arthritis: A Narrative Review

“…An alternative approach is the use of nanoparticles. Although confirmation in the clinical setting is still required, such nanoparticulated drugs (nanodrugs) have recently gained recognition in drug delivery for a number of therapeutic areas [ 118 , 119 , 120 ]. Indeed, Geiger et al showed that nanoparticles carrying IGF-1 successfully penetrated bovine cartilage within 2 days of application [ 121 ].…”