الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Osteoarthritis (OA),a serious disease,affects whole joint tissues resulting in structural changes in cartilage, synovial inflammation and bone remodeling.
Management of OA primary focuses on pain reduction and function restoration using anti-inflammatory and analgesic agents torelief symptoms only but they can’t retard deterioration and structural alterations of OA.
Therefore,disease-modifying OA drugs (DMOADs) were investigated based on good understanding of key factors contributed to OApathogenesis to retard jointdegeneration for repairing the existing joint damage.
However, a lot of challengesfacing DMOAsresultedin an unmet clinical need for OA modifying therapeutics such as associatedside effects and lowpoorbioavailability.
Diacerein, a prodrug converted to rhein (RH)prior to its systemic absorption showing its promising chondroprotective effect.
Unfortunately, loworalbioavailability and substantial sideeffect (diarrhea)limited its effective OA therapy.
Therefore, delivery of suchpromising agents through efficient drug delivery systems might be a meaningful step towards OA therapy. Intra-articular (IA) drug delivery represents many benefits giventhe localized nature of OAoffering high drug concentration whileminimizing substantial side effects associated to systemic one.
Whilerapid clearancefollowing IA administrationfenestrated these benefits. To optimize the IA route, several strategies were developed regarding increasing the joint residence time. Recently, nanocarriers attracted a significant attention in this regard. The present thesis aimed at developing and evaluating suitable drug delivery systems for local administration of rhein(RH), active metabolite of diacerein,with the aim of improving therapeutic efficacy, reduced side effects and targeted the diseased tissue with cartilage homing agents like chondroitin sulfate and phospholipids to overcome disadvantages associated with conventional preparations.
The work in this thesis is divided into two. parts