RICERCA ITALIANA     

PHYSICAL PROPERTIES OF POLYMER-BASED NANOSTRUCTURED BIOMATRICES

Università degli Studi di Parma

Abstract

The research project aims at improving the knowledge of structural and dynamic properties of matrices based on natural and synthetic polymers. The objectives of this study are twofold:
- to improve our understanding of basic aspects of solvent-solute interactions in chemical and physical gel systems;
- to make use of this detailed picture to optimize the tailoring of polymer- and biopolymer-structures for biomedical applications, namely: nanostructures for modulated drug delivery
Two types of materials will be studied in the project:
i) matrices based on poly (vinyl alcohol) suitably modified in order to obtain hydrogel microspheres with a large surface/volume ratio and therefore with a high capacity of loading scarcely soluble drugs (typically anti-tumor drugs) otherwise difficult to deliver directly.
ii) matrices based on hyaluronic acid, HYA, a biopolymer present in the sinovial fluid of mammals. We will investigate a derivative of HYA with just 4 % of the repeating units grafted with hydrophobic alkyl chains. This modified HYA is able to form, even at very low polymer concentrations (c 10 g/L), stable hydrogels with remarkable viscoelastic properties.
Our aim is to impart to the new systems properties, absent in the starting materials, that make it possible to tune the biomatrix characteristics in response to external thermodynamic parameters that can be relevant in bio-technological applications. Examples are the >>>

Principal Investigator

Antonio Deriu Università degli Studi di PARMA

Research Objectives

The project aims at investigating the structural and dynamic properties of novel biomatrices (made up from gels and nanogels) suitable for controlled drug delivery. In particular we intend to study:
i) matrices based on poly (vinyl alcohol) suitably modified in order to obtain hydrogel microspheres with a large surface/volume ratio and therefore with a high capacity of loading scarcely soluble drugs (typically anti-tumor drugs) otherwise difficult to deliver directly.
ii) matrices based on hyaluronic acid, HYA, a biopolymer present in the sinovial fluid of mammals. We will investigate a derivative of HYA with just 4 % of the repeating units grafted with hydrophobic alkyl chains. This modified HYA is able to form, even at very low polymer concentrations (c 10 g/L), stable hydrogels with remarkable viscoelastic properties.
Our aim is to obtain and characterize systems providing an appreciable encapsulation of insoluble bioactive molecules, an enhanced bio-availability of the drug, a localized (focal) release with a controlled kinetics, a limited (if any) immunologic response, and an overall acceptability from the patients.
The carriers will be obtained in gel and nanogel form. The accurate design of these materials is crucial as it determines the localization and the efficacy of the release of the carried drug. A further very relevant item that has to be investigated in detail is the water-macromolecule interaction mechanism and its role in >>>

First Results

Our aim is to obtain and characterize novel biomatrices suitable for 'smart' drug delivery providing an appreciable encapsulation of insoluble bioactive molecules, an enhanced bio-availability of the drug, a localized (focal) release with a controlled kinetics, a limited (if any) immunologic response, and an overall acceptability from the patients.

The main deliverable will therefore be the optimised preparation protocols for the two classes of biomatrices investigated:
i) matrices based on poly (vinyl alcohol) in form of hydrogel microspheres with a large surface/volume ratio and therefore with a high capacity of loading scarcely soluble drugs.
ii) matrices based on a modified form of hyaluronic acid (with about 4% of the repeating units grafted with hydrophobic alkyl chains) that is able to form, even at very low polymer concentrations (c 10 g/L), stable hydrogels with remarkable viscoelastic properties and enhanced resistance to enzymatic degradation.

The information obtained on PVAMA gels will also be useful as a starting point for further studies on new multifunctional systems obtained from PVA. As an example we may quote recent studies that demonstrated that by incapsulating diethylenetriamine pentaacetic acid (Gd-DTPA) into biodegradable polymeric microparticles it is possible to enable noninvasive monitoring of their local intravesical delivery by magnetic resonance imaging [1]. In a similar context, PVAMA-NiPAAM >>>

Timescale

24 months

National and international background

In recent years pharmaceutical research tackled a range of complex problems in connection with the development of new therapeutic methodologies as for instance: gene- therapies, targeted release of drugs, molecular imaging. The design of novel active pharmaceutical systems requires an integrated approach in order to maximize the effectiveness of the active species by its interaction with a suitable carrier able to eventually release the drug in a controlled way and in a specific region. Usually these drug platforms are hydrogel matrices: multi-component system constituted by an aqueous solution and a polymeric moiety imparting different functions to the matrix, as responsiveness to external stimuli, affinity to receptors, controlled drug release. These systems form nowadays a relevant family of biomaterials and their study will further expand in the next years [1-3]. The aim is to obtain systems able to time tune and to localize the drug release; therefore bio-availability and controlled release should be the benchmarks achievable by using new polymer platforms. In this respect, two types of biomatrices with different physical and chemical characteristics will be investigated in the present project:
(i) injectable micro/nano-hydrogels based on poly (vinyl alcohol);
(ii) macroscopic hydrogels based on hyaluronic acid.
The most important characteristics of systems (i) are:
- Very large surface/volume ratio, a property of major importance for >>>