Molecular characterization of a ,b -poly(asparthylhydrazide) a new synthetic polymer for biomedical applications R. Mendichi a, * , G. Giammona b , G. Cavallaro b , A. Giacometti Schieroni a a Istituto di Chimica delle Macromolecole (CNR), Via Bassini 15, 20133, Milan, Italy b Dipartimento di Chimica e Tecnologie Farmaceutiche, Universita ` degli Studi di Palermo, Via Archirafi 32, 90123, Palermo, Italy Received 20 October 1998; accepted 15 December 1998 Abstract a ,b -Poly(asparthylhydrazide) (PAHy) is a new synthetic polymer that exhibits interesting properties and is a candidate for biomedical applications. In this article the characterization of PAHy polymer by multi-angle laser light scattering (MALS) and single-capillary viscometer (SCV) detectors on-line to a size exclusion chromatography (SEC) system is reported. The SEC–MALS–SCV system furnishes exhaustive and consistent characterization of the PAHy polymer. Further, it is possible to characterize the PAHy polymer through conven- tional SEC and universal calibration. The universal calibration method gives intrinsic viscosity and dispersity very close to those measured by the absolute detectors; instead the weight-average molar mass is approximately 8% lower. This finding means that the chromatographic separation of PAHy polymer is fundamentally based on its hydrodynamic volume. By the SEC–MALS–SCV system the constants of the Mark–Houwink–Sakurada equation were also estimated.  1999 Elsevier Science Ltd. All rights reserved. Keywords: a ,b -Poly(asparthylhydrazide); Molecular characterization; Drug carrier 1. Introduction A great deal of interest has been aroused by the use of polymeric materials in the controlled drug delivery [1]. In this field such materials can be used to perform implants, hydrogels, micro- and nanoparticles, supramolecular micel- lar assemblies or polyelectrolytic complex containing drugs, polymeric drugs and polymeric carriers to which drugs can be linked by chemically and/or enzymatically hydrolyzable bonds [2,3]. In the latter case macromolecular prodrugs are obtained, which is able to deliver compound at the desired rate within the target compartment [4]. The major determi- nant of the pharmacokinetic characteristics in vivo of a macromolecular prodrug seems to be the macromolecule rather than the drug or targeting moiety [5]. Ideal macro- molecular carriers should be easily synthesized at low cost, freely water-soluble, non-toxic, non-immunogenic and well characterized from the physico-chemical point of view [6]. Large importance in the distribution and elimination patterns of a macromolecular system is attributed to its physico-chemical properties, including molar mass distribu- tion (MMD) and molecular size [5,6] and to its structural properties such as the presence of hydrophilic and/or hydro- phobic portions, the incorporation of charged groups, the possible chemical dishomogeneities [7], etc. Also confor- mational properties of the macromolecules and their affinity with the medium can influence the biodistribution into the organism [4]. Studies of renal excretion and retention on animals performed on polyaspartamides at different molar mass demonstrating that clearance rate decreases with increasing molar mass [8]; but comparing with different materials it should seem better to relate the clearance of macromole- cules to size rather than molar mass, since globular proteins and synthetic macromolecules of comparable molar mass have usually different sizes. Moreover, the flexible structure of the latter permits them to pass through glomerular pores by “end-up” motion allowing higher molar mass molecules to pass [7]. Unlike natural macromolecules, synthetic macro- molecules are polydisperse. Therefore, it is important to characterize these macromolecules not only by their average molar mass but also by their MMD. To be eliminated from the organism, the whole MMD must be under the threshold for glomerular filtration. Studies on the biological fate of some preparations of [ 14 C] Polyvinylpyrrolidone with the same molar mass but different polydispersities provided evidence for the importance of the MMD [9]. The prepara- tion with higher polydispersity (containing a fraction of macromolecules with higher molar mass) was found to be Polymer 40 (1999) 7109–7116 0032-3861/99/$ - see front matter  1999 Elsevier Science Ltd. All rights reserved. PII: S0032-3861(99)00079-8 * Corresponding author.