title: Complex formation between the anionic polymer (PAA) and a cationic drug (procaine HCI): characterization by microcalorimetric studies.
abstract: OBJECTIVE
  Due to the importance of drug-polymer interactions in, inter alia, drug loading/release, supramolecular assemblies and DNA delivery for gene therapy, the aim of this study was therefore to establish the mechanism of interaction between a model polymer (Polyacrylic acid, PAA) and a model drug (procaine HCl).
  
  
  METHODS
  This was performed by studying the effect of salt (KCl) concentration on their heat released values using Isothermal Titration Microcalorimetry (ITM). The integrated released heat data were computer fitted to a one class binding model and the thermodynamic parameters (Kobs, deltaH, and N) were determined.
  
  
  RESULTS
  As the KCl concentration was increased, Kobs decreased thus establishing the salt dependence of the interaction. The linear variation of deltaGobs with deltaSobs indicated that their interaction was entropically driven. The stoichiometry of the interaction was calculated to be one procaine molecule per monomer of PAA. Dissection of the total observed free energy at each KCI concentration indicated that the contribution of the non-electrostatic attractions to the interaction of PAA with procaine HCl was greater than those of the electrostatic attractions.
  
  
  CONCLUSIONS
  We have shown that the interaction between PAA and procaine HCl is dependent upon the presence of counterions (monovalent ions) and is mainly entropically driven. The calculated stoichiometry indicated that one procaine HCl molecule neutralised one carboxylic acid group on PAA. Although electrostatic interactions were necessary for initiating complex formation, the non-electrostatic forces were dominant in stabilising the PAA-procaine HCl complex.
authors.affiliation: School of Pharmaceutical Sciences, University of Nottingham, UK.
authors.forename: T
authors.initials: T
authors.lastname: Govender
authors.forename: T
authors.initials: T
authors.lastname: Ehtezazi
authors.forename: S
authors.initials: S
authors.lastname: Stolnik
authors.forename: L
authors.initials: L
authors.lastname: Illum
authors.forename: S S
authors.initials: SS
authors.lastname: Davis
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D000779:Anesthetics, Local / Q000737:chemistry*; D000838:Anions; D001665:Binding Sites; D002151:Calorimetry / Q000379:methods; D002412:Cations; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D007700:Kinetics; D011189:Potassium Chloride / Q000737:chemistry; D011343:Procaine / Q000737:chemistry*; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D000180:Acrylic Resins; D000779:Anesthetics, Local; D000838:Anions; D002412:Cations; C006903:carbopol 940; D011343:Procaine; D011189:Potassium Chloride