drug delivery in arthritis

Question 1

what are advantages of articular injection?

Answer 1

As able to target area directly, increases bioavailability of the drug and reduces off target effects

lower drug cost

Question 2

what are some disadvantages of articular drug injection?

Answer 2

biochemical properties of drug varies as it interacts with hydrophobic and hydrophilic surfaces

increased infection risk

unable to overcome lymphatic clearance

Question 2

what is meant by bioavailability of a drug?

Answer 2

the % drug which reaches the target site

Question 3

what is meant by release kinetics of a drug?

Answer 3

the rate at which a drug is released from its delivery system to the environment

Question 4

what do current OA treatments focus on?

Answer 4

aim to ease the symptoms of the disease
> pain
> joint swelling

Question 4

how is secondary OA different from ideopathic OA?

Answer 4

there is a known cause for OA e.g
> post-traumatic
> congentical
> metabolic

Question 5

name some current OA treatments

Answer 5

drugs - NSAIDS, corticosteroid injection

recommend - lifestyle change + physio

Question 6

why are targeted OA treatments difficult to develop?

Answer 6

OA affects multiple tissues making up the joint and each tissue undergoes pathological changes
> degenerative
> inflammatory
> functional + structural changes

these changes vary during stages of disease too

Question 7

where could a OA drug target?

Biologically

Answer 7

anatomically = bone, cartilidge, SF

cellular target = chondrocyte, synoviocyte, immune cells

molecular = pain, repair, remodelling, inflam pathways,

Question 8

what is a DMARD?

Answer 8

disease modifying drug

unfortunately no such DMARD exisits yet for OA

Question 9

what are characteristics of ideal drug?

Answer 9

able to be targeted to tissue of interest
controlled release
miminal side effects

Question 10

how do patients present as a barrier for OA drug design?

Answer 10

variable disease progression with late+early onset

so this patient variability can affect optimal drug efficacy

Question 11

why is the OA joint a barrier to drug design?

Answer 11

its avascular so alternatives to systemic delivery need to be developed

complex joint anatomy so many tissues to target

Hard to penetate as its a closed system

Question 12

how would a pro-i environment affect drug delivery design?

Answer 12

hostile environment could compromise stability of the drug and make it susceptible to degradation before reaching its target site

Question 13

how do intra-articular injection overcome OA drug delivery barriers?

Answer 13

rate of passage of molecules into S.F by capillaries is size dependent

so injection can immediately enter SF

Question 14

why is the Articular cartilage tissue a barrier for OA drug delivey?

Answer 14

AC tissue is heterogenous and structured into different zones and regions

collegen fibre orientation and chondrocyte shape varies across the tissue

composition of ECM changes thoughout the tissue making drug
Penetrance difficult

Question 15

how can we tell histologically that OA is happening?

Answer 15

loss of toludine blue staining

normally stains GAGs like aggrecan but in OA the protease ADAMTS5 cleaves aggrecan