June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Biodegradation of poly(esteramide)s - utility in ophthalmic drug delivery
Author Affiliations & Notes
  • George Mihov
    DSM, Geleen, Netherlands
  • Madalina Natu
    DSM, Geleen, Netherlands
  • Guy Draaisma
    DSM, Geleen, Netherlands
  • Silvana di-Silvestre
    DSM, Geleen, Netherlands
  • Jens Thies
    DSM, Geleen, Netherlands
  • Footnotes
    Commercial Relationships George Mihov, DSM (E); Madalina Natu, DSM (E); Guy Draaisma, DSM (E); Silvana di-Silvestre, DSM (E); Jens Thies, DSM (E)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 261. doi:
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      George Mihov, Madalina Natu, Guy Draaisma, Silvana di-Silvestre, Jens Thies, DSM Drug Delivery Research; Biodegradation of poly(esteramide)s - utility in ophthalmic drug delivery. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):261.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: Amino acid based poly(esteramide)s “PEAs” are a new family of biodegradable polymers based on amino acids, dicarboxylic acids and diols. This class of polymers is being explored as drug delivery vehicles in a variety of ophthalmic therapies. We report an extensive research on polymer degradation addressing degradation kinetics, mechanism and degradation products. The results provide valuable input not only for material safety but reveal how the intrinsic polymer degradation properties could be employed to engineer novel therapeutic solutions.

Methods: Test articles of PEA polymers were prepared by solvent casting. The degradation was studied in PBS buffer (0.1 M, pH 7.4) at 37˚C. Relative molecular weight of the remaining polymer articles was determined by GPC. PEA samples containing horseradish peroxidase (HRP) were prepared by solvent-casting of HRP suspension in 10 % polymer solution in ethanol. Next the protein was released in PBS buffer and analysed.

Results: The investigated PEA polymers degrade at physiological conditions via a complex mechanism exhibiting overall linear degradation kinetics. Importantly, the hydrolysis affects predominantly the ester bonds along the polymer chain. This allows a fine tuning and good predictability of material biodegradation properties based on polymer structural features. Furthermore, the intrinsic polymer degradation mechanism contributes for the good material API compatibility even at advanced stages of polymer chain cleavage. In a model experiment was demonstrated that HRP retains its enzymatic activity for more than two months when incorporated in PEA matrix. The study showed that the polymer degradation can contribute to the API release kinetics as well.

Conclusions: PEAs offer a versatile polymer platform for ophthalmic drug delivery. PEA polymers degrade slowly at physiological conditions via hydrolytic cleavage of the ester linkages along of the polymer chain. PEAs show good compatibility with acid sensitive API’s which is of particular importance for sustained delivery of biopharmaceuticals or hydrolysis susceptible molecules such as latanoprost. Furthermore, the intrinsic polymer degradation properties could be employed for engineering of optimal API release kinetics. Since PEAs are well tolerated in the ocular environment and can be manufactured to be loaded with different classes of drugs, PEAs would be ideal for sustained delivery of drugs to the posterior segment.

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