Emulsion assisted nonsteroidal anti-inflammatory drug delivery system for the osteoarthritis treatment
Date
2023-07-24
Authors
Journal Title
Journal ISSN
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Publisher
Saudi Digital Library
Abstract
Osteoarthritis (OA) is one of the considerable chronic health conditions worldwide. In the UK, 8.75
million people were receiving OA treatment. Currently, there are no disease-modifying drugs, and
treatment relies on the management of pain associated with OA. The delivery of OA drugs is
challenging because the cartilage is dense, avascular (i.e., has no blood vessels), and relies on
diffusion to transport nutrients and drugs to the cells. Moreover, cartilage matrix is composed of
anionic proteoglycans that can repel negatively charged drugs, making it difficult for OA drugs to
penetrate through the matrix and reach the target cells. Additionally, most OA drugs are hydrophobic,
so an appropriate technique is required to deliver them inside cartilage. A novel and efficient
emulsion-based local delivery of OA drugs coated with poly beta-amino ester polymers (POLY-X)
into cartilage was proposed.
In this project, nonsteroidal anti-inflammatory drugs as a model drug for OA treatment were
examined. The characterization of the developed delivery system and its efficacy in native (non
treated) and glycosaminoglycan (GAG) depleted cartilage was assessed by measuring the zeta
potential and size, amount of drug uptake and retention in the cartilage. In addition, the ability of the
developed drug delivery system to inhibit cytokine (IL-1α) induced glycosaminoglycan and collagen
degradation, as well as the loss of cell viability in cartilage explants were tested.
The data showed that the developed emulsion delivery system exhibited enhanced and prolonged
drug localisation not only on non-treated cartilage tissues but also on GAG depleted sample resulting
in a higher amount of drug uptake and retention in cartilage compared to the control, and the
difference was statistically significant (p < 0.05). Furthermore, the developed emulsion delivery
system protects the viability of the chondrocyte cell and provides a significant increased (p <0.01) in
glycosaminoglycan and collagen content compared to IL-1α treated cartilage and similar to untreated
control. The percentage of sGAG and collagen loss was 3 to 5 times higher in IL-1α treated cartilage
compared to the untreated and developed drug delivery system treated groups.
This study proved that modified emulsion-based therapy could provide a substantial improvement in
the treatment of OA to maintain cartilage properties and improve OA outcomes.
Description
Keywords
Osteoarthritis, Polybeta amino ester polymer, NSAIDs, emulsion