Development of Anti-VEGF Prolonged Release Drug Delivery System Containing PLL Dendrimer and Hyaluronic Acid

In this study we aimed to develop anti-vascular endothelial growth factors (anti-VEGF) drug delivery systems that long-term sustained release using dendrimer technology and to evaluate its possible cytotoxic effects on the retina pigment epithelial cells (ARPE-19) and the irritation potential by Hen...

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Bibliographic Details
Published in:Russian journal of bioorganic chemistry 2022-12, Vol.48 (6), p.1348-1361
Main Authors: Gedik, G., Oztabag, C. K., Sarp, O., Nazli, H., Tiranbesli, G., Kurt, A. H., Dinc, E., Ayaz, L.
Format: Article
Language:English
Subjects:
Biochemistry
Biomedical and Life Sciences
Biomedicine
Bioorganic Chemistry
Clarity
Drug carriers
Drug delivery systems
Epithelium
Evaluation
Growth factors
Hyaluronic acid
Irritation
Life Sciences
Lysine
Mathematical analysis
Organic Chemistry
Particle size
Polydispersity
Spectrophotometry
Sustained release
Zeta potential
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Summary:In this study we aimed to develop anti-vascular endothelial growth factors (anti-VEGF) drug delivery systems that long-term sustained release using dendrimer technology and to evaluate its possible cytotoxic effects on the retina pigment epithelial cells (ARPE-19) and the irritation potential by Hen’s Egg Test on a chorioallantoic membrane (HET-CAM) analysis. The drug carrier gel formulation was prepared by adding hyaluronic acid (HA) after bevacizumab (BEV) was complexed with poly-L-lysine (PLL) dendrimer. The formulations were determined by the particle size, polydispersity index (PDI) values, zeta potential, pH, optical clarity, and their content. The UV- spectrophotometric analytical methods were developed, validated and applied for the kinetic studies. Prolonged BEV release from formulations has been observed for up to 21 days. Cell viability was evaluated with the XTT assay. VEGF and BEV levels in the medium were measured using a human VEGF and BEV ELISA kit, respectively. HET-CAM assays were conducted to determine the irritation potential. The clarity of gel formulation was found to be “clear” and satisfactory (double +). The pH of gel formulation ranged between 6.39 and 6.95. The zeta potential of formulations ranged between +3.9 and –1.5 mV. The particle size of formulations ranged between 15 and 302 nm. The loading efficiency (LE) of the complex formulation was found 79.04%. The formulation’s kinetic behavior was determined by the Higuchi and Korsmeyer–Peppas model. The formulations did not cause any irritation. According to the results obtained, gel formulation was innovative, effective and suitable for treatment. However, animal experiments and clinical studies should also be performed.
ISSN:1068-1620
1608-330X
DOI:10.1134/S1068162022060115