Screening of poly-beta amino ester coated emulsion of ketorolac for cartilage delivery.

Osteoarthritis (OA) is a prevalent chronic health condition necessitating effective treatment strategies. Globally, there were 86 million people with incident knee osteoarthritis in 2020. Pain management remains the primary approach to OA as the nature of cartilage poses challenges for drug delivery. An emulsion-based delivery system, using a class of positively charged and hydrolysable polymers (poly-beta-amino-esters) to coat oil droplets containing drugs, has been shown to enhance and prolong drug localization in ex vivo cartilage models. As the properties of the polymers used in this technology strongly depend on the monomers used in the synthesis, this study presents the screening of a wide range of PBAEs as droplet coating agents and using ketorolac as a model of nonsteroidal anti-inflammatory drugs. The emulsions prepared with this PBAE library were characterized, and drug localisation and retention were evaluated in both native and glycosaminoglycan (GAG) depleted cartilage ex vivo models. Optimal candidates were identified and tested in an ex vivo model showing the ability to protect chondrocyte cell viability and increase both GAG and collagen contents in cartilage exposed to cytokine (IL-1α) simulating acute cartilage damage. This work demonstrates the potential of PBAE coated emulsion as a delivery system for effective drug delivery in OA treatment.

Poly beta amino ester coated emulsions of NSAIDs for cartilage treatment.

Delivering drugs directly into cartilage is still the major challenge in the management and treatment of osteoarthritis (OA) resulting from the aneural, avascular and alymphatic nature of an articular cartilage structure. Progress has been made in the design of drug delivery systems that enhance corticosteroid uptake and retention in cartilage; however also non-steroidal anti-inflammatory drugs (NSAIDs) are prescribed for patients affected by OA and a drug delivery system specifically designed for this drug category is currently unavailable. We developed an approach based on the preparation of NSAID oil-in-water emulsions coated with poly-beta-amino-esters (PBAEs) to exploit the cartilage penetrating ability of such polymers and the high solubility of drugs in oil. These emulsions containing different NSAIDs (indomethacin, ketorolac, diclofenac and naproxen) exhibited enhanced and prolonged drug localisation not only in healthy cartilage tissues but also in early-stage OA samples. The critical role of the PBAE layer on oil droplets was established along with the retained biological activity of the drug as glycosaminoglycan (GAG) and collagen degradation induced by interleukin-1 (IL-1) was prevented by the novel technology. Oil-in-water coated emulsions are very flexible and cost-effective drug delivery systems and such an approach presented here could provide a substantial improvement in the therapeutic treatments of OA and thus patients' outcomes.

Polymer colloids as drug delivery systems for the treatment of arthritis.

The most common types of arthritis are osteoarthritis (OA) and rheumatoid arthritis (RA) which are themain causes of disability and pain among older people. Current treatment of arthritis mainly consists of oral and intra-articular medications. Despite the efficacy of the intraarticular injections over the oral treatment, it is still limited by the rapid clearance of the injected drug. Therefore, a rational design of drug delivery systems (DDSs) able to delivery drugs in controlled manner and for required period of time to the arthritis joint is a key in developing safe and effective formulations for OA and RA. In this paper various colloidal systems like nanoparticles, liposomes, cationic carriers, hydrogels, and emulsion-based carriers were presented and discussed in light of their use and efficacy as delivery systems to transport therapeutics for arthritis treatment. Factors influencing the delivery efficacy such as size, charge, structure, drug uptake, retention and its release profile alongside with cytocompatibility and safety were addressed. Moreover, the advantages and disadvantages of the different colloidal systems were emphasised.