Elsevier

European Polymer Journal

Volume 40, Issue 8, August 2004, Pages 1683-1690
European Polymer Journal

Timolol maleate release from pH-sensible poly(2-hydroxyethyl methacrylate-co-methacrylic acid) hydrogels

https://doi.org/10.1016/j.eurpolymj.2004.03.012Get rights and content

Abstract

Multifunctional polymeric materials were obtained from poly(methacrylic acid-co-2-hydroxyethyl methacrylate), to be used as a raw material in the manufacture of contact lens and as drug delivery systems. Poly(methacrylic acid-co-2-hydroxyethyl methacrylate) was prepared by free-radical polymerization in aqueous solution at 60 °C using potassium persulfate (KPS) as initiator and N,N-methylenebisacrylamide (BIS) as cross-linker agent. The dynamic and equilibrium swelling properties of dry glassy poly(methacrylic acid-co-2-hydroxyethyl methacrylate) polymeric networks were studied as a function of pH and methacrylic acid (MAA) content. The water content increase as MAA content and pH increase. Timolol maleate delivery from poly(MAA) and poly(2-hydroxyethyl methacrylate) (HEMA) homopolymers was studied and the results show a Fickian diffusion behavior.

Introduction

In the modern medicine [1], [2], polymeric materials have been used for a wide range of applications because much of them are biocompatible with blood, tissues, cells, i.e., in the human body. The actual tendency is directed to the development of materials that are assimilated by the organism producing minimum collateral effects. That is the case of the hydrogels.

Hydrogels are a cross-linked hydrophilic polymer networks that can absorb more than 100 times their dry weight in water, giving the physical characteristics similar to soft tissue. Swelling and hydration occur without dissolution of the polymer, since the process of cross-linking creates an insoluble networks. In addition, hydrogels are highly permeable, which facilitates exchange of oxygen, nutrient and other water-soluble metabolites.

In the last decades, chemically and physically diverse hydrogels have became standard materials for scaffolds for the regeneration of new skin, encapsulation of cells and regeneration of tendons and cartilage [3], [4], [5], [6], [7], corneal implants, contact lenses and intelligent controlled drug release devices for site-specific drug delivery [8], [9], [10].

In this sense, the aim of this work is to study the swelling behavior of the methacrylic acid (MAA) and 2-hydroxyethyl methacrylate (HEMA) copolymers, prepared by radical copolymerization in aqueous solution, to be evaluated as a multifunctional material, i.e., used both, as a contact lens and a timolol maleate controlled delivery system.

Section snippets

Materials

Methacrylic acid (MAA, Fluka A.G.) and 2-hydroxyethyl methacrylate (HEMA, Fluka A.G.) were vacuum distilled at 63 °C/12 mmHg and 50 °C/50 mmHg, respectively, prior to used in order to remove the inhibitor. In HEMA vacuum distillation, hydroquinone was added to prevent polymerization. Cross-linking agent, N,N-methylenebisacrylamide (BIS, Fluka A.G.) and potassium persulfate (0.001% N) (KPS, Merck) were used without further purification. Water used in all the studies was double distilled and

Results and discussion

In the previous stage of the polymer dissolution, the solvent molecules go into the polymeric mass, swell it until chain separation and its incorporation into the solution in opposition to the intermolecular forces (e.g. van der Waals, electrostatics, etc.) that exist between them. However, if the polymer is no soluble, a solvent diffusion to the polymeric mass and from he polymeric mass to the medium will only exist. Then, the polymer swelling will occur. The equilibrium swelling will be

Conclusions

2-Hydroxyethyl methacrylate (HEMA) and methacrylic acid (MAA) hydrogels have been synthesized and influence of the hydrogel composition and pH in the swelling and the timolol maleate release at 37 °C have been studied. As the MAA content in the hydrogel increases its swelling is higher, because of the hydrophilic character of that monomer. In the same way, hydrogel composition affects to the drug release process too. Diffusion coefficients are higher as the MAA content in the hydrogel

Acknowledgements

The authors thank the MCYT (projects number MAT2000-0768-CO2-02 and PPQ2000-287-CO2-02), Gobierno Vasco and the Universidad del Paı́s Vasco for their financial support.

References (22)

  • A.S Hoffman

    Adv. Drug Deliv. Rev.

    (2002)
  • K.T Nguyen et al.

    Biomaterials

    (2002)
  • L.G Griffith

    Acta Mater.

    (2000)
  • N.A Peppas et al.

    J. Controlled Release

    (1997)
  • Y Qiu et al.

    Adv. Drug Deliv. Rev.

    (2001)
  • K Shoutha

    Biomaterials

    (1995)
  • N.B Graham

    Hydrogels: their future, Part II, Med. Dev. Technol.

    (1998)
  • N.A Peppas

    Hydrogels in medicine and pharmacy

    (1987)
  • N.A Peppas et al.

    Eur. J. Pharm. Biopharm.

    (2002)
  • K Park

    Controlled drug delivery: challenges and strategies

    (1997)
  • E Schatch

    J. Controlled Release

    (1996)
  • Cited by (0)

    View full text