Insulin delivery to the brain using intracranial implantation of alginate-encapsulated pancreatic islets

Abstract

There is increasing evidence supporting a link between cognitive dysfunctions and impaired brain insulin signalling. Insulin therapy has previously been tested as an approach to ameliorate brain insulin resistance and deficiency in patients with various brain disorders. However, current strategies for insulin delivery to the brain may induce severe hypoglycaemia when injected peripherally or show poor uptake when delivered intranasally. Recently, we have shown that intracranial transplantation of naked pancreatic islets increased insulin content in the brain and attenuated cognitive dysfunctions without altering peripheral glucose homeostasis in rats with schizophrenia-like syndrome. In this study, we show that intracranial implantation of 50 pancreatic islets encapsulated in disc-shaped alginate is sufficient to elevate insulin content in the rat brain. Three weeks after implantation, the islets displayed intact morphology, intensive hormone staining and glucose-sensitive insulin release. The ultrapure alginate with high guluronic acid content used for islet encapsulation demonstrated good biocompatibility and stability after intracranial implantation. All implanted animals were normoglycaemic and normoinsulinaemic. In conclusion, the intracranial implantation of a small amount of alginate-encapsulated islets is an efficient tool for metabolically regulated insulin delivery to the brain. Copyright © 2017 John Wiley & Sons, Ltd.

A Drug‐Eluting 3D‐Printed Mesh (GlioMesh) for Management of Glioblastoma

“…The ease of cross‐linking is another advantage of alginate that facilitates the manipulation of this biomaterial to construct complex 3D structure. Notably, alginate has been used in brain implants in vivo without inducing inflammatory response in the brain environment . Additionally, the incorporation of polymeric microspheres into the 3D bioprinted mesh offers the advantage of immobilizing the microspheres and achieving a prolonged TMZ release at the tumor site.…”

“…Notably, alginate has been used in brain implants in vivo without inducing inflammatory response in the brain environment. [34][35][36] Additionally, the incorporation of polymeric microspheres into the 3D bioprinted mesh offers the advantage of immobilizing the microspheres and achieving a prolonged TMZ release at the tumor site. Figure 3.…”

Novel Formulations of C-Peptide with Long-Acting Therapeutic Potential for Treatment of Diabetic Complications

“…Besides the preparation of PEG-peptide conjugates to improve the peptide circulation half-life in vivo and, consequently, to diminish the dose necessary for efficient administration, the application of polymer particles for peptide drug delivery can be also matter of choice [16,17,18]. Despite the fact that the works devoted to the development of efficient delivery systems of C-peptide were not discovered, several examples on preparation of encapsulated forms of insulin can be found in the current literature [19,20,21,22,23]. The polymer particles of different nature were applied to encapsulate insulin.…”

Formulation, physicochemical characterization and in vitro evaluation of human insulin-loaded microspheres as potential oral carrier

“…These days, there has been a lot of interest in the investigation and feasibility of non-invasive routes for insulin delivery and their product developments in the pharmaceutical industry. These non-invasive routes (Khafagy et al 2007 ) include oral (Al-Remawi et al 2017 ), nasal (Bloch et al 2017 ), buccal (Kumria and Goomber 2011 ), pulmonary (Pfützner and forst 2005 ), transdermal (Leeladurga et al 2016 ), ocular (Lee et al 2002 ) and rectal (du Plessis et al 2010 ) drug delivery systems (Owens 2002 ; Cefalu 2004 ).…”