Novel Random Triblock Copolymers for Sustained Delivery of Macromolecules for the Treatment of Ocular Diseases

Abstract

The objective of this study is to design, develop, and synthesize novel random triblock (RTB) copolymers for sustained delivery of macromolecules. RTB copolymers have not been utilized for the delivery of macromolecules for ocular diseases. RTB copolymers comprising of polyethylene glycol, glycolide, and ɛ-caprolactone blocks were synthesized and assessed for their molecular weights and purity using 1H-NMR spectroscopy, gel permeation chromatography, FTIR (functionality), and XRD (crystallinity). No toxicity was observed when ocular cell lines were treated with RTB copolymers. These materials were applied for encapsulation of peptides and proteins (catalase, IgG, BSA, IgG Fab fragment, lysozyme, insulin, and octreotide) in nanoparticles. Particle size ranged from 202.41 ± 2.45 to 300.1 ± 3.11 nm depending on the molecular size and geometry of proteins/peptides. Polydispersity indices were between 0.26 ± 0.02 and 0.46 ± 0.07 respectively. Percentage entrapment efficiency and drug loading ranged from 83.44 ± 2.24 to 45.35 ± 5.53 and 21.56 ± 0.46 to 13.08 ± 1.35 respectively depending on molecular weights of peptides or proteins. A sustained in vitro release of macromolecule was observed over 3-month period. These results suggest that RTB copolymers may be suitable for sustained delivery systems for various macromolecules for different diseases including ocular diseases.

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Acknowledgements

The authors would like to thank Dr. James Murowchick (Department of Geosciences, UMKC) for XRD analysis, Dr. Zhonghua Peng (Department of Chemistry, UMKC) for his assistance in GPC analysis, and Dr. Kun Cheng (Department of Pharmaceutical Sciences, UMKC) for allowing us to utilize freeze dryer.

Funding

This work was supported by National Institute of Health grants RO1 EY 09171-14, RO1 EY 10659-12, and Genentech. This work is also financially supported by Graduate Assistant Fund (GAF), UMKC Women’s Council.

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Correspondence to Ashim K. Mitra.

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Ngatuni, M.J., Trinh, H.M., Pal, D. et al. Novel Random Triblock Copolymers for Sustained Delivery of Macromolecules for the Treatment of Ocular Diseases. AAPS PharmSciTech 19, 3871–3885 (2018). https://doi.org/10.1208/s12249-018-1172-3

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KEY WORDS

  • random triblock copolymers
  • nanoparticles
  • ocular delivery
  • protein and peptide
  • sustained drug delivery
  • controlled release