Effects of polyelectrolyte conformation, charge density and ion specificity in polyelectrolyte and polyelectrolyte-drug interaction

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Effects of polyelectrolyte conformation, charge density and ion specificity in polyelectrolyte and polyelectrolyte-drug interaction

Hugerth, Andreas M. (författare): Uppsala universitet,Institutionen för farmaceutisk kemi

(creator_code:org_t)

ISBN 9155447244
Uppsala : Acta Universitatis Upsaliensis, 2000
Engelska 39 s.
Serie: Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, 0282-7484 ; 227

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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)

Abstract Ämnesord

Stäng

The central theme is how the structural characteristics of sulphated polyelectrolytes and theirinteraction with counter- and coions determine the degree of polyelectrolyte self-association (gelformation), interaction with oppositely charged polyelectrolyte and polyelectrolyte-amphiphilic druginteraction in protolytic solvent medium. Such knowledge is essential for understanding and regulatingthe interaction between polyelectrolytes as well as between polyelectrolytes and a drug substance in apharmaceutical formulation and for its fate in the human organism.The gel formation of the sulphated polyelectrolyte ê-carrageenan was found to be dependent on theextent of inter-chain helical association and thus the nature of the polyelectrolyte counterions. This wasshown from the relationship between the gel-sol melting temperature of the hydrophobic microdomains(T0), the fraction of polymer in helical conformation at T0, and the storage modulus of the samples inthe gel-state. Interaction between the oppositely charged polyelectrolytes carrageenan and chitosanresulted in the formation of polyelectrolyte complexes with a charge ratio of unity. However, in casesof inter helical association of carrageenan chitosan acted as a bridging element producing complexeswith a charge ratio below unity. This mechanism may be used to control the charge ratio ofpolyelectrolyte complexes.The solvation characteristics of the polyelectrolyte counterions also affected the polyelectrolyte-amphiphilic drug interaction (amitriptyline). The binding isotherm was shifted to a higher concentrationof free amphiphile according to the counterion sequence Li+ < Na+ < K+ < Rb+ ≈Cs+. The change inGibbs free energy per monomer amphiphile originating from exchanging the counterions (Li+ for Cs+),was of the order of kT. This is of the same order of magnitude as that obtained by significantlychanging the hydrophobicity of the amphiphilic drug molecule. Increasing the polyelectrolyte chargedensity decreased the critical aggregation concentration, increased the degree of cooperativity andincreased the magnitude of ion specific effects. Furthermore, the dependence of the. critical aggregationconcentration on ionic strength was linear and the polymer flexibility affected the efficiency of thepolycounterion properties of the polyelectrolyte. The binding isotherms, micropolarity, microviscosityand surface tension indicated the amitriptyline-polyelectrolyte interaction to be qualitatively andquantitatively similar to that observed for "typical" cationic surfactants.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medicinal Chemistry (hsv//eng)

Nyckelord

Pharmaceutical chemistry
Farmaceutisk kemi
Pharmaceutical chemistry
Farmaceutisk kemi
Physical and Inorganic Pharmaceutical Chemistry
fysikalisk och oorganisk farmaceutisk kemi

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