How to Develop Drug Delivery System Based on Carbohydrate Nanoparticles Targeted to Brain Tumors

Abstract

Brain tumors are the most difficult to treat, not only because of the variety of their forms and the small number of effective chemotherapeutic agents capable of suppressing tumor cells, but also limited by poor drug transport across the blood-brain barrier (BBB). Nanoparticles are promising drug delivery solutions promoted by the expansion of nanotechnology, emerging in the creation and practical use of materials in the range from 1 to 500 nm. Carbohydrate-based nanoparticles is a unique platform for active molecular transport and targeted drug delivery, providing biocompatibility, biodegradability, and a reduction in toxic side effects. However, the design and fabrication of biopolymer colloidal nanomaterials have been and remain highly challenging to date. Our review is devoted to the description of carbohydrate nanoparticle synthesis and modification, with a brief overview of the biological and promising clinical outcomes. We also expect this manuscript to highlight the great potential of carbohydrate nanocarriers for drug delivery and targeted treatment of gliomas of various grades and glioblastomas, as the most aggressive of brain tumors.

Keywords: blood–brain barrier; drug delivery; glioblastoma; nanoparticles; natural polymers; polysaccharides.

Figure 1

Structural formulas of some carbohydrates (cellulose and its derivatives, chitosan, pectin, hyaluronic acid, and alginate) and their possible modifications, on the basis of which it is possible to obtain various materials, including NPs [30,31,32,33,34,35,36,37,38]. The chemical modifications of polysaccharide nanoparticles are necessary to enhance their ability to cross the BBB and reach the target brain cells and for the attachment of targeting moieties and drugs. These modifications promote charge and active site setting, which allows nanoparticles with controlled drug release and biodegradation ability to be designed.

Figure 2

Structural formulas of chitin and chitosan in uncharged and charged forms. The presented polysaccharides can contain both types of glucosamine residues connected by O-glycoside bonds simultaneously.

Figure 3

General scheme of pectins’ structure: (A) general image of pectins with structural units; (B) various modifications of galacturonic acid in the composition of pectins. The figure is based on data from [52].

Figure 4

Structure of alginate based on data from [69].

Figure 5

Main types of NPs and their parameters. Reprinted with permission from [118], copyright year 2023, copyright owner Elsevier, Journal of Controlled Release.