Development Of An Edta-Functionalized Oxidized Starch Nanohydrogel For Nose-To-Brain Delivery Of Lithium Carbonate

Original Research | 2026 | Volume 1 | Issue 2 | Page 161-176

1. Abhijeet Singh, Department of Pharmacy, HRIT University, Duhai Ghaziabad

2. Dr. Meenu Singh, Assistant Professor, Department of Pharmacy, HRIT University, Duhai Ghaziabad

Development Of An Edta-Functionalized Oxidized Starch Nanohydrogel For Nose-To-Brain Deliv.

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ABSTRACT

Lithium carbonate remains the gold-standard mood stabiliser for bipolar disorder, but chronic oral therapy is limited by its narrow therapeutic index, low and variable central nervous system (CNS) bioavailability, and systemic renal, thyroid, and neurological toxicity that together drive poor adherence. Direct nose-to-brain delivery, which exploits the olfactory and trigeminal neuronal pathways to bypass hepatic first-pass metabolism and the blood-brain barrier (BBB), offers a route to concentrate lithium in the CNS while lowering the systemic dose and its associated toxic burden. This paper proposes and rationalises the development of an EDTA-functionalised, oxidised-starch nanohydrogel as an intranasal carrier for lithium carbonate. Native starch is first oxidised (e.g., via TEMPO/hypochlorite or periodate oxidation) to introduce carboxyl and aldehyde functionalities that enable ionic cross-linking into a nanohydrogel network and provide sites for covalent EDTA conjugation through carbodiimide (EDC/NHS) chemistry. EDTA, a well-documented calcium-chelating permeation enhancer, is proposed to transiently and reversibly loosen Ca2+-dependent nasal epithelial tight junctions, thereby promoting paracellular transport of the nanohydrogel-entrapped drug, while the mucoadhesive, hydrophilic oxidised-starch matrix is expected to prolong nasal residence time and protect the drug from rapid mucociliary clearance. The proposed formulation strategy, physicochemical characterisation plan (particle size, zeta potential, polydispersity index, FTIR, DSC, XRD, SEM/TEM, drug loading and encapsulation efficiency, in vitro release, ex vivo nasal permeation, and mucoadhesion), and pre-clinical evaluation framework (biodistribution, brain/blood ratio, histopathology, and safety) are described in detail. Anticipated advantages of the system include reduced systemic lithium exposure, improved brain targeting efficiency, biodegradability and biocompatibility of the starch-based carrier, and a controlled-release profile suitable for once- or twice-daily intranasal dosing. Potential challenges, including nasal mucociliary clearance, enzymatic degradation, EDTA-related mucosal irritancy at high concentrations, and scale-up reproducibility, are also discussed. This work is intended as a literature-grounded design and evaluation roadmap for a starch-based, ion-chelator-functionalised nanohydrogel platform for CNS-targeted lithium therapy.

Keywords: Lithium carbonate; Nose-to-brain delivery; Oxidized starch; Nanohydrogel; EDTA; Permeation enhancer; Bipolar disorder; Intranasal drug delivery; Blood-brain barrier; Mucoadhesion