Cation polysaccharides

HYDROPHOBE MODIFIED CATIONIC POLYSACCHARIDES FOR TOPICAL MICROBICIDE DELIVERY... 

Hydrophobe Modified Cationic Polysaccharides for Topical Microbicide Delivery... 

A new class of water-soluble materials [10,11], was developed as a result of such design parameters that will be referred to as double substituted cationic cellulose ethers (DCEs). These materials contain both a cationic substituent and a hydrophobic substituent, attached to a cellulose ether backbone. The use of a double-substituted hydrophobe modified cationic polysaccharide is fundamentally different from current commercial vaginal formulations, which rely exclusively on nonionic or anionic vehicles. 

In the course of screening N9/cationic polymer formulations, an important observation was made. Hydrophobe modified cationic polysaccharides [33] displayed unique sperm impedance, but not spermicidal, properties. By contrast, the related non-hydrophobe modified material was devoid of that effect. It is important to state that hydrophobe incorporation into water soluble polymers, at the desired level for optimum efficacy, is complex. Chemical efficiency can be low in the derivatized polymer and solubility characteristics change dramatically. Of the various hydrophobes evaluated in these studies, the —C12H25 hydrophobe was preferred. 

We were successful earlier in achieving anioiuc/cationic complexes with glycosaminoglycans, e.g., hyaluronic acid/cationic polysaccharide compositions [44], now used in personal care applications. Those compositions are substantive, stable and user-friendly. Unfortunately, despite the highly anionic nature of hyaluronic acid (and other glycosaminoglycans), these materials do not block viral infections [39]. Furthermore, as shown by the in vivo rabbit irritation studies, such compositions displayed minimal irritation [13]. 

Substantivity [24] of a series of hydrophobe modified cationic polysaccharides to skin, hair, and an anionic vinyl substrate (skin substitute) was shown using ESCA, even after repeated washings with distilled water. ESCA, being an expensive technique not suitable for screening purposes. 

Hydrophobe, cationic modifled cellulose ethers (DCFs) are drug delivery vehicles speciflcally designed to interact with mucosae. DCE s are closely related to cationic polysaccharides used safely and effectively for many years in topical personal care products. 

Erode, G. L. in Vaginal Microbicide Formulations Workshop, Rencher, W. R (Ed), Lippincott-Raven (Philadelphia, PA), Chemical/physical principles in microbiocide formulations with emphasis on hydrophobe modified cationic polysaccharides-a new excipient class, 1998, Chap. 5, pp. 38-50. 

Dunlap et al., 1997 Godbey et al., 1999), dendrimers (Chen et al., 2000) and cationic polysaccharide, chitosan (Erbacher et al., 1998). It was suggested that DNA condensation is induced by multivalent cations where approximately 90% of its charge is neutralized, and that divalent cations have insufficient potency to attain the charge neutralization on such a level (Wilson and Bloomfield, 1979 Bloomfield, 1991, 1996 He etal., 2000 Stevens, 2001). 

Chitosan is a cationic polysaccharide produced from the deacetylation of chitin, a component of crab and shrimp shells [7,57,58], Chitin is composed of units of 2-deoxy-2-(acetylamino) glucose joined by glycosidic bonds that form a linear polymer. Ilium et al. [7,57,58] demonstrated the ability of chitosan to increase the bioavailability of insulin and other small peptides and polar macromolecules in different animal models. In both the sheep and rat models, the addition of chitosan at concentrations of 0.2%-0.5% to nasal formulations of insulin resulted in significant increases in plasma insulin and reductions in blood glucose. Reversibility studies indicated that the effect of chitosan on the nasal absorption of insulin... 

Yudovin-Farber I, Domb AJ (2007) Cationic polysaccharides for gene delivery. Mat Sci Eng 27 595-598... 

Azzam T, Raskin A, Makovitzki A et al (2002) Cationic polysaccharides for gene delivery. Macromolecules 35(27) 9947-9953... 

Chitosan is a linear cationic polysaccharide made up of copolymers of glucosamine and A-acetylglucosaminc. It is commercially obtained by alkaline deacetylation of chitin [53, 68] and has been used for the nasal delivery of a number of drugs. The usefulness of chitosan in the enhancement of nasal absorption was reported first by Ilium [69]. Later, Ilium and his group also published experimental results indicating that solution formulations with 0.5% chitosan promoted the absorption of nasally administered insulin in rat and sheep [70]. 

The nature of complex-formation between cations and monosaccharides is now well understood this knowledge should form a firm basis for the study of cation-polysaccharide interactions. 

Cationic Polysaccharides in Regenerative Medicine Challenges and Perspectives... 

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