[22] Dextran and inulin conjugates as drug carriers

doi:10.1016/S0076-6879(85)12024-0

Methods in Enzymology

Volume 112, 1985, Pages 285-298

https://doi.org/10.1016/S0076-6879(85)12024-0 Get rights and content

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This chapter discusses the dextran and inulin conjugates as drug carriers. Dextran and inulin are pharmacologically inert, and as a result, the pharmacological properties of their conjugates are due to the linked drug. Many drugs conjugated to a polysaccharide carrier, such as dextran and inulin, exhibit improved chemical and biological stability as well as changes in their pharmacokinetics. By esterification of a drug with dextran and inulin, it is possible to produce a slow-release form of the drug. On the other hand, linking a drug or a biologically active substance by a nonpolar bond to dextran, it is possible to prolong its serum lifetime and pharmacobiological activity and to selectively reach the RES tissues, while the nonpolar bond to inulin gives the final conjugate a urinary tract tropism. In all these conjugates (by ester or nonpolar linkage), the polysaccharide carrier improves the chemical and chemicophysical stability of the linked drug.

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Glycoside hydrolase family 70 (GH70) glucansucrases produce α-d-glucan polysaccharides (e.g. dextran), which have different linkage composition, branching degree and size distribution, and hold potential applications in food, cosmetic and medicine industry. In addition, GH70 branching sucrases add single α-(1→2) or α-(1→3) branches onto dextran, resulting in highly branched polysaccharides with “comb-like” structure. The physico-chemical properties of these α-d-glucans are highly influenced by their linkage compositions, branching degrees and sizes. Among these α-d-glucans, dextran is commercially applied as plasma expander and separation matrix based on extensive studies of its structure and physico-chemical properties. However, such detailed information is lacking for the other type of α-d-glucans. Aiming to stimulate the application of α-d-glucans produced by glucansucrases, we present an overview of the structures, production, physico-chemical properties and (potential) applications of these sucrose-derived α-d-glucan polysaccharides. We also discuss bottlenecks and future perspectives for the application of these α-d-glucan polysaccharides.
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In the present study we therefore aimed to extend previous findings on adsorption of small fluorophores at surfaces of injured cartilage [19] to examine differential adsorption of fluorescently labeled native and modified dextrans to cracked and intact surfaces of mechanically injured cartilage. Dextrans are excellent choices for carrier molecules because they are natural, biodegradable and pharmacologically inert and have been widely used in other medical applications [20–27]. In addition, dextrans are available commercially in different molecular weights and have numerous hydroxyl groups that can be easily used for chemical modification or conjugation to imaging agents [22,23].
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Chemotherapy is one of the primary treatment mechanisms for treating cancer. Current chemotherapy is systemically delivered and causes significant side effects; therefore the development of new chemotherapeutic agents or enhancing the effectiveness of current chemotherapeutic could prove vital to patients and cancer care. The purpose of this research was to develop a new conjugate composed of doxorubicin (chemotherapeutic) and inulin (polysaccharide chain) and evaluate its potential as a new therapeutic agent for cancer treatment. The synergistic effect of inulin conjugated to doxorubicin has allowed the same cytotoxic response to be maintained or improved at lower doses as compared to doxorubicin. Supporting results include cytotoxicity profiles, calf thymus DNA binding studies, confocal microscopy, and transport studies.
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Natural polymers such as dextran, starch, cellulose, chitosan, sodium alginate, lignin and their derivatives are more promising than synthetic polymers in food and biomedical applications due to their better biodegradability and biocompatibility (Fernández-Pérez et al., 2011; Kurita, Ikeda, Yoshida, Shimojoh, & Harata, 2002; Ma, Yang, Kennedy, & Nie, 2009; Sánchez-Chaves, Rodríguez, & Arranz, 1997; Zhang, Jin, Liu, & Du, 2001). A variety of methods have been described to transform the polysaccharide carrier into a reactive derivative that originally lacked the appropriate functionality (Molteni, 1985; Schacht, Vermeersch, Vandoorne, Vercauteren, & Remon, 1985). Microwave assisted esterification is one of the facile ways to modify polysaccharides.
A microwave assisted facile synthesis of a fluorescent 6-O-naphthylacetyl agarose (NA-agarose) employing carbodiimide chemistry (dicyclohexylcarbodiimide/4-dimethylaminopyridine) has been described. NA-agarose was characterized by TGA, GPC, UV spectrophotometry, fluorescence spectroscopy, FT-IR, ¹H and ¹³C NMR spectra, exhibiting that in NA-agarose the naphthylacetyl group was attached to the backbone of the agarose polymer. The hydrolysis of NA-agarose in heterogeneous aqueous phase showed that the 1-naphthyl acetic acid (NAA), a plant growth regulator, got released in a controlled manner, the release rate being dependent on the hydrophilicity of the polymer adduct as well as on pH and temperature. The fluorescence emission (λ_max 332 nm) of NA-agarose (1 × 10⁻³ M) in ethylene glycol was significantly higher (ca. 82%) than that of the molar equivalent of NAA content in the product i.e. 0.08 mg in 1 × 10⁻³ M solution. The resulting polymer would be of potential utility as a sustained release plant growth regulator and sensory applications.
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[22] Dextran and inulin conjugates as drug carriers

Publisher Summary

Ann. Chim.

Nature (London)

Ann. Pharm. Poznam