Intra articular drug delivery system final

Intra articular drug delivery system is most useful for treating incurable disease such as rheumatoid arthritis

1. GOVT. COLLEGE OF PHARMACY, KARAD GOVT.COLLEGE OF PHARMACY, KARAD

2. PRESENTED BY: Miss.Shital Baburao khade Under the guidance of: miss. M.P .Kurade “SUSTAIN RELEASE INTRA-ARTICULAR DRUG DELIVERY IN RHEUMATOID ARTHRITIS”

3. Anotomy of normal joint verses arthritis joint Cartilage Bone Tendon Synovial fluid- Hyaluronidase Synovial membrane

4. Introduction of Rheumatoid arthritis- Rheumatoid arthritis-30,000 people dead Disorder of the joint in which inflammation of the joint and hence erosion of the bone take place.

5. Factors in RA-

6. Diagnosis establishment   Complete blood count. Comprehensive metabolic panel. Rheumatoid factor. Antibodies to citrullinated peptide including antigens. C-reactive protein [CRP]. Erythrocyte sedimentation rate[ESR].

7. Placebo effect Novel mechanism direct targeting the pathophysiological RA. Local Drug delivery to the joint. To Avoid conventional barrier to entry to joint following systemic . Increase bioavailability and Decrease dose via IA . No oral NSAIDS available superior to IA placebo with resp. pain reduction Marked difference in Effect of size between oral and IA. To Avoid side effect due to extra- articular delivery. To Prolong action of drug and site specificity. To Avoid toxicity to liver, lung, kidney, Heart , GIT irritation ,neural toxicity due to oral and systemic delivery of anti rheumatic drug Why the need intra- articular drug delivery?

8. Rheumatoid nodule. Cardiopulmonary diseases. Eye disorder – Keratoconjunctivitis of sjorens syndrome. Rheumatoid vasculitis. Neurologic disease – carpel tunnel syndrome , Cervical myelopathy. Cervical myelopathy. Feltys syndrome. Toxicity to other tissues Disease caused due Extraarticular drug delivery

9. LIMITATION TO INTRAARTICULAR DRUG DELIVERY Fast eliminated from joint. Requiring numerous injection and hence cause infection , rashes Cuase joint disability Inflammatory response to intraarticular injection Crystal induced arthritis, observed in 10% people Pain or swelling at the site of injection, may occur in 20% people Septic arthritis

10. Modulation in intra articular drug delivery- Sustain release[increase retention time] Modulators Hydrogel Nano/micro particle Liposomes Polymers Magnetic nanoparicles Chitosan, PLGA, PEG ,

11. Micro and nanoparticles- Localise drug delivery at the site of infection Increase retention time

12. MODULATORS Polymeric micelles Advantage– Easy to design ,Encapsulation of a wide-range of therapeutics , Controlled and/or sustained release Protection of encapsulated drugs from in vivo degradation and Clearance Disadvantages- Limited polymers for use ,Lack of stability ,Deficiency in methods for large-scale production   Poly(ethylene glycol) (PEG) Water soluble Advantages- Excellent biocompatibility ,Low toxicity ,High drug loading capacity Increased dwell time Highly permissible environment for facile diffusion ,FDA approved Disadvantages- Rapid drug release , Inhibit cellular uptake ,Inhibit endosomal escape Poly lactic-co-glycolic acid (PLGA) Advantages- Specifically tailored to be biocompatible and biodegradable ,Exhibits a wide-array of erosion times Modification in surface properties provide better interaction with biological materials , FDA approved Disadvantages- Negative charge of PLGA particles is disadvantageous for particle uptake PLGA particles can not be sterile filtered Particle size may limit crossing of biological barrier

13. advantages of sustain release intraarticular delivery Increase retention time Reduction in frequency of injection and doses Reduction in frequency of infection Increase concentration of drug and reduction dose Prolong duration of action of drug Reduction in joint disabilities due to intraarticular injection

14. treatment A) Medication B) Patient education C) Surgery   1 Methotrexate alone or in Combinations (with leflunomide )   2 Immunomodulatory agents (Cyclosporine, tacrolimus, azathioprine, cyclophosphamide)   3 Traditional DMARD 8 corticosteroid- (Gold Compounds, D penicillamine, prednisolone , betamethasone Sulfasalazine , antimalarials)   4 Cytokine inhibitors 9. Hyaluronate injection IL-1 antagonists (IL-1Ra, IL-1 soluble receptors)   5TNF-alpha 10.Biologic agents et anercept, adalimumab   6 NSAID 11.Autologus blood product Diclofenac , Ibuprofen IL-1 ANTAGONIST   7 DMARD-  

15. Recent approaches in IA Nonsurgical synovectomy with radionuclides Gene therapy Cell based therapy Magnetic nanoparticle Gold nanoparticles

16. Treatment of RA by IA route/ Application Drug Brand name Dose Caution Side effect 1.BOTULINUM NEUROTOXIN INJ. BOTOX More than 12 weeks Pregnancy, Eaton la bert syndrome 2.BETAMETHASONE CELESTONE 0.5-2ml, 3 to4 inj, 2wk interval Diabetes Increase BP, appetite bruising 3.Trimcinolone Kenalog 40 40 mg/ml for 1wk Idiopathic Redness at inj site , pain Kenalog 20 20mg /ml for 1wk Thrombocytopenia Itching 4Trimcinolone hexiacetonide ARISTOSPAN 2-20 mg for 3-4 wks 5.Adalimumab HUMIRA 40 mg for past 6 month Pneumonia, hepatitis Redness , pain ,Itching

17. Drug Brand name Dose Caution Side effect Etanerce -pt ENBREL 50mg for 4wk CHF , TB Rash , pain ,infection Inflixima-b INFLECTRA 10-20 mg for 8wks CHF , Hepatitis Headache, fungal infection Leflunomide ARAVA 12.5-15mg once a wk upto 25 mg for 6 month Ras h , pain , Itching Prednisolone RAYOS >30 mg lasted for 5 wk Diabetese, high BP Pain at inj site , redness , itching

18. CONCLUSION The intraarticular injection of therapeutic agents is an attractive strategy for the local treatment of joint diseases. Most joints are accessible to accurate injection, especially when using image guidance. Given that such injections cannot be administered too frequently, it is preferable to use reagents that have a Prolong therapeutic effect . However, soluble agents are rapidly cleared from joints, regardless of the size of the drug, and this transience remains a major barrier to successful therapy. Intraarticular injection became popular in the latter half of the twentieth century owing to the introduction of Intraarticular corticosteroids. Today, this treatment and the injection of hyaluronate into joints with RA form the major uses of this technique. Interest in delivering recombinant proteins, autologous blood products, particles, cells and gene therapy vectors to diseased joints continues to mount. Local delivery in this fashion is potentially safer, less expensive and more effective than parenteral delivery. Reducing the need for burdensome repeated injections of soluble therapeutics will, however, require better drug formulations with more lasting efficacy.

19. Thank you!