Intranasal Polymeric and Lipid-Based Nanocarriers for CNS Drug Delivery

Abstract

Nanomedicine is currently focused on the design and development of nanocarriers that enhance drug delivery to the brain to address unmet clinical needs for treating neuropsychiatric disorders and neurological diseases. Polymer and lipid-based drug carriers are advantageous for delivery to the central nervous system (CNS) due to their safety profiles, drug-loading capacity, and controlled-release properties. Polymer and lipid-based nanoparticles (NPs) are reported to penetrate the blood–brain barrier (BBB) and have been extensively assessed in in vitro and animal models of glioblastoma, epilepsy, and neurodegenerative disease. Since approval by the Food and Drug Administration (FDA) of intranasal esketamine for treatment of major depressive disorder, intranasal administration has emerged as an attractive route to bypass the BBB for drug delivery to the CNS. NPs can be specifically designed for intranasal administration by tailoring their size and coating with mucoadhesive agents or other moieties that promote transport across the nasal mucosa. In this review, unique characteristics of polymeric and lipid-based nanocarriers desirable for drug delivery to the brain are explored in addition to their potential for drug repurposing for the treatment of CNS disorders. Progress in intranasal drug delivery using polymeric and lipid-based nanostructures for the development of treatments of various neurological diseases are also described.

Nano-Based Drug Delivery Systems: Potential Developments in the Therapy of Metastatic Osteosarcoma—A Narrative Review

“…This controlled release mechanism can lead to improved drug efficacy, reduced side effects, and enhanced patient compliance. For instance, instead of taking a pill every few hours, a patient might receive a PLGA-based implant that steadily releases the drug over weeks or even months [ 143 , 144 , 145 ]. Furthermore, the safety profile of PLGA is well established.…”

Intranasal Therapy in Palliative Care

“…Some reports compared intranasal and intravenous drug administration in animal models and tissue lines [ 11 , 26 ]. Animal models showed that concentrations in brain tissue may be higher after intranasal administration than after intravenous administration [ 72 ]. In the case of drugs acting mainly on the CNS, this is an extremely valuable discovery.…”

Nucleic acid-based therapeutics for the treatment of central nervous system disorders

“…While PK studies of intranasal administration are limited, there is evidence to suggest that NBTs administered via this route can reach the olfactory bulb as soon as 5 min post-administration and more distal regions of the brain as soon as 30 min in the mouse brain ( Renner et al, 2012 ; Falcone et al, 2014 ). Nanotechnological modifications including polymeric nanoparticles and solid lipid nanoparticles can make the process of uptake more efficient and successful ( Maher et al, 2023 ). As previously discussed, the size, surface qualities, and biocompatibility of these nanocarriers allow for efficient uptake and bypassing of the BBB ( Begines et al, 2020 ).…”

“…Considering this, modifications can be made to the drug to allow for longer residence time. One such modification is the conjugation of chitosan, a mucoadhesive agent which functions by electrostatically interacting with the negatively charged epithelial surfaces and thus enhancing the drug’s duration of stay in the nasal cavity ( Maher et al, 2023 ). A study exploring the intranasal administration of a chitosan-based nanoparticle containing HTT targeting siRNA demonstrated therapeutically significant lowering of HTT mRNA in the mouse brain ( Sava et al, 2021 ).…”

“…While effective, IT administration proves invasive and is not easily accessible to all patients. Alternative administration routes such as intranasal administration are currently being explored and hold significant potential ( Maher et al, 2023 ).…”