1- Issues with Current Therapy

- Anticholinergics block muscarinic receptors in other smooth muscles causing dry

mouth and eyes, dizziness, constipation, nausea, and blurred vision.

- It also binds to M2 receptors on the heart causing cardiac side effects

- Oxybutynin is selective for M1 receptors and can cross the BBB. Thus, it negatively
effects CNS causing hallucinations and confusion

- Anticholinergics has serious cognitive side effects on people over 65 of age

Doses of 50 mg or higher of beta-3 agonist are associated with increased heart rate and
blood pressure.

2- Comparison between Current and Novel Therapies

Oxybutynin IR Lipotoxin

Efficacy - Significantly increases bladder capacity - Significantly decreases urinary

frequency and nocturia
- Decreases urgency and frequency
- Statistically significantly decreases pain
and urgency

Safety - Potential CNS adverse reactions in -Less systemic side effects

geriatric
- Risk of UTI, urinary retention, and pain
- Metabolic load and possible drug-drug
interaction

Tolerabilit - Generally poor due to bothersome side - Well tolerated by patients

y effects
- General improvement in quality of life
- Poor adherence and increased patient
discontinuation
3- Issues with Lipotoxin with Suggested Solutions:
- Large molecular weight (150 kDa)  treat with protamine sulfate to increase
permeability to urothelium

- Unstable during sterilization  use glass fiber filtration and 0.45 µm cellulose filters

- Short shelf-life of less than 2 years  add antioxidants + use non-oxygenated

aqueous solution

- Physical instability  add cholesterol to strengthen lipid membrane + store at 4℃

with no light exposure

- Risk of bleeding 

- Risk of infection  Keep good hygiene and use water-based antiseptics before and
during procedure

- Risk of urinary retention  recommend patients to use catheterization until

symptoms improved.

4- Why Lipotoxin is an optimization over Oxybutynin:

 Lipotoxin offers high, local drug concentration and extended duration of drug
contacting the bladder. Thus, it increases drug uptake through endocytosis.

 Lipotoxin is superior in reducing systemic side effects caused by Oxybutynin due to

its local administration.

 Liposome encapsulates the drug preventing it from being degrade by enzymes in the
urine, which optimize drug design.