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

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-

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

8.  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?

9. 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

11. 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

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

13. MICRO AND NANOPARTICLES-
Localise drug delivery at the site of infection
Increase retention time

14. 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

15. 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

16. TREATMENT
A) Medication B) Patient education C) Surgery
1 Methotrexatealone 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
etanercept, adalimumab
6 NSAID 11.Autologus blood product
Diclofenac , Ibuprofen IL-1 ANTAGONIST
7 DMARD-

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

18. Treatment of RA by IA route/ Application
Drug Brand name Dose Caution Side effect
1.BOTULINU
M
NEUROTOXI
N INJ.
BOTOX
More than
12 weeks Pregnancy, Eaton la bert syndrome
2.BETAMETH
ASONE
CELESTONE 0.5-2ml, 3
to4 inj, 2wk
interval
Diabetes Increase BP, appetite
bruising
3.Trimcinolo
ne
Kenalog 40 40 mg/ml
for 1wk
Idiopathic Redness at inj site , pain
Kenalog 20 20mg/ml for
1wk
Thrombocyto
penia
Itching
4Trimcinolo
ne
hexiacetoni
de
ARISTOSPAN
2-20 mg for
3-4 wks
5.Adalimum
ab
HUMIRA 40 mg for
past 6
month
Pneumonia,
hepatitis
Redness , pain ,Itching

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

20. 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.

21. Thank you!