title: Poly(aspartic acid) with adjustable pH-dependent solubility.
abstract: Poly(aspartic acid) (PASP) derivatives with adjustable pH-dependent solubility were synthesized and characterized to establish the relationship between their structure and solubility in order to predict their applicability as a basic material for enteric coatings. Polysuccinimide, the precursor of PASP, was modified with short chain alkylamines, and the residual succinimide rings were subsequently opened to prepare the corresponding PASP derivatives. Study of the effect of the type and concentration of the side groups on the pH-dependent solubility of PASP showed that solubility can be adjusted by proper selection of the chemical structure. The Henderson-Hasselbalch (HH) and the extended HH equations were used to describe the pH-dependent solubility of the polymers quantitatively. The estimate provided by the HH equation is poor, but an accurate description of the pH-dependent solubility can be found with the extended HH equation. The dissolution rate of a polymer film prepared from a selected PASP derivative was determined by fluorescence marking. The film dissolved rapidly when the pH was increased above its pKa. Cellular viability tests show that PASP derivatives are non-toxic to a human cell line. These polymers are thus of great interest as starting materials for enteric coatings.
  
  
  
  Poly(amino acid) type biocompatible polymers were synthesized for future use as pharmaceutical film coatings. To this end, we tailored the pH-dependent solubility of poly(aspartic acid) (PASP). It was found that both the solubility and the pKavalues of the modified PASP depended strongly on composition. Fluorescent marking was used to characterize the dissolution of a chosen PASP derivative. In acidic media only a negligible amount of the polymer dissolved, but dissolution was very fast and complete at the pH values that prevail in the small intestine. As a consequence, enteric coatings based on such PASP derivatives may be used for drug delivery in the gastrointestinal tract.
authors.affiliation: Department of Physical Chemistry and Materials Science, Budapest University of Technology and Economics, Műegyetem rkp. 3., H-1111 Budapest, Hungary.
authors.forename: Csaba
authors.initials: C
authors.lastname: Németh
authors.affiliation: Department of Physical Chemistry and Materials Science, Budapest University of Technology and Economics, Műegyetem rkp. 3., H-1111 Budapest, Hungary.
authors.forename: Benjámin
authors.initials: B
authors.lastname: Gyarmati
authors.affiliation: Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia.
authors.forename: Timur
authors.initials: T
authors.lastname: Abdullin
authors.affiliation: Department of Physical Chemistry and Materials Science, Budapest University of Technology and Economics, Műegyetem rkp. 3., H-1111 Budapest, Hungary.
authors.forename: Krisztina
authors.initials: K
authors.lastname: László
authors.affiliation: Department of Physical Chemistry and Materials Science, Budapest University of Technology and Economics, Műegyetem rkp. 3., H-1111 Budapest, Hungary. Electronic address: aszilagyi@mail.bme.hu.
authors.forename: András
authors.initials: A
authors.lastname: Szilágyi
mesh_terms: D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008962:Models, Theoretical; D010455:Peptides / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D012995:Solubility
chemical_list: D010455:Peptides; C017645:polyaspartate; C025252:poly-DL-succinimide; D001224:Aspartic Acid
keywords: Biopolymers; Enteric coatings; Poly(aspartic acid); Solubility models; pH-dependent solubility