학술논문
PLGA nanocapsules as a delivery system for a recombinant LRP-based therapeutic.
Document Type
Academic Journal
Author
Bernert M; School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, South Africa.; Bignoux MJ; School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, South Africa.; Madhav C; School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, South Africa.; Gqeba S; School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, South Africa.; Otgaar TC; School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, South Africa.; Morris G; School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, South Africa.; Weiss SFT; School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, South Africa.; Ferreira E; School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, South Africa.
Source
Publisher: John Wiley & Sons Ltd Country of Publication: England NLM ID: 101580716 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2211-5463 (Electronic) Linking ISSN: 22115463 NLM ISO Abbreviation: FEBS Open Bio Subsets: MEDLINE
Subject
Language
English
Abstract
Telomerase activity is directly affected by the laminin receptor precursor (LRP) protein, a highly conserved nonintegrin transmembrane receptor, which has been shown to have therapeutic effects in ageing, and age-related diseases. Recently, it has been found that overexpression of LRP-FLAG, by plasmid transfection, leads to a significant increase in telomerase activity in cell culture models. This may indicate that upregulation of LRP can be used to treat various age-related diseases. However, transfection is not a viable treatment strategy for patients. Therefore, we present a nanoencapsulated protein-based drug synthesised using poly(lactic-co-glycolic acid) (PLGA) nanocapsules for delivery of the 37 kDa LRP protein therapeutic. PLGA nanocapsules were synthesised using the double emulsification-solvent evaporation technique. Different purification methods, including filtration and centrifugation, were tested to ensure that the nanocapsules were within the optimal size range, and the BCA assay was used to determine encapsulation efficiency. The completed drug was tested in a HEK-293 cell culture model, to investigate the effect on cell viability, LRP protein levels and telomerase activity. A significant increase in total LRP protein levels with a concomitant increase in cell viability and telomerase activity was observed. Due to the observed increase in telomerase activity, this approach could represent a safer alternative to plasmid transfection for the treatment of age-related diseases.
(© 2024 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
(© 2024 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)