Customised drug delivery system

Introduction
 Drug delivery systems that are designed to release the drug as per the

need of the individual or specific patient.

 Therapy with right drug at right dosing in the right patient.

 Ability to look at a patient on an individual basis will allow for a more

accurate diagnosis and specific treatment plan.

 Customised medicines are prepared based on each patient’s medical

history, needs, genetics, health conditions and other factors.

 Genetic and metabolic data will allow drugs to be tailored to patients

sub group.

 The customised drug release profiles required will necessitate the use

of multiple types of technologies like extended release, sustained

release and timed pulsatile release.

 Much of the innovation will come from developing a better

understanding of the patient rather than the identification of new

molecules.

Definition
  Customised drug delivery also termed personalised medicine is a

medical procedure that separates patients into different groups with

medical decisions, practices to individual patient based on their

predicted response or risk of disease.

 It is also known as smart drug delivery.

 The terms personalised medicine contain P4 medicines.

The Person

 Their DNA

 Exposure to environmental factors.

 Types and amount of stress they experience.

 What they eat.

Advantages of customised drug delivery

 Better matching patients to drugs instead of trial and error.

 Eliminate life-threating adverse reactions.

 Reduce cost of clinical trails by quickly identifying total failures and

favourable response for particular backgrounds.

 Improved efficacy of drugs.

  Dosage can be controlled for the patients who need lower doses or

with the needs of each individual patient.

 Any allergic creating ingredient can be skipped and a customised

medicine can be produced for a particular individual.

 One size fits all prescription medicines cannot meet so customised

medicines are the only way to better health.

Example 1: Treatment of Arrhythmia

 Response to currently used antiarrhythmic therapies is vary from

person to person, with some patients gets clear-cut benefit such as
reduction in paroxysmal atrial fibrillation, while other derive no
benefit.

Advance genetic and genomic technologies:

 GAWS (Genome wide association studies) has been used in the

cardiac electrophysiological field and has resulted in the identification
of several loci involved in long QT syndrome plays an important role
in the calcium signaling pathways in myocardial repolarization, and
many other ECG parameters.

Bioelectronic medicine

 Bioelectronic medicine are electronic devices can be used to analyze

and modulate the electrical activity within nerves system.
  Bioelectronic medicines are new and innovative approach of
personalized drug delivery system. These are used to diagnosis of any
disease, clinical testing and therapy.

 These are used to diagnosis of any disease, clinical testing and

therapy. The main feature of bioelectronic medicine as it stimulates
electrical impulse to nerves system and body tissues instead of
chemical treatment.

Example 2: Treatment of cancer

 The customised drug delivery Systems is also called smart drug

delivery.
 This can be made possible by making it in form of nanomedicine
these nanoparticles loaded with drug and targeted to specific parts of
the body where there is solely diseased tissue, avoiding interaction
with healthy tissue.
 This can be done either by passive or active targeting.

In cancer:

 The drug delivery by passive targeting is based on EPR effect

(Enhance permeation and retention) which provides rather modest
tumour specificity with 20-30% in delivery increase compared to
normal organs.

 Doxil and caelyx are some of nanocarriers of passive targeting

through EPR effect are successfully used in clinics.
  The active targeting is further improvised in cancer through

Cellular, vascular, nuclear, acidity of TME (tumour micro

environment).

Cellular targeting:

 Tumour cell targeting is performed by nanocarriers.

 Targeting is based on density i.e., higher density higher the targeting
efficiency.
 The ligand or receptor interaction occurs only at high density
receptors, nanoparticles pass and enhance cell penetration.
 Eg: folic acid conjugated to silica nanoparticles

Vascular targeting:

 It targets angiogenic endothelial cells which are adjacent to tumour

cells this will reduce blood supply to the tumour and deprive cancer
cells from oxygen and nutrients with subsequent hypoxia and
necrosis.
 Eg: RGD peptides (arginine glycine aspartic acid) grafted on
nanoparticles or nanocarriers like nanotubes, nanographene oxide
carrying anticancer drugs.
 RGD targets integrin present cancer cells because they are
upregulated compared to healthy cells.
Nuclear targeting:

 Some treatments need more precise level which is the drug delivery at
organelle level for examples nucleus, lysosomes, mitochondria,
endoplasmic reticulum.
 Example: Doxorubicin involves oxidative damage and topoisomerase
II inhibition within the nucleus by using gold nanoparticles by
reducing size to 30nm with PEG and Peptide because only gold
nanoparticles below 9nm penetrates nuclear pore complex which
controls the communication between cytosol and nucleus but show
fast clearance.

Targeting the mildly acidic tumour environment:

 Tumour tissues are more acidic than normal PH because the

cellular metabolism in tumour cells switch to glycolysis with the
formation of lactic acid.
 Eg: Estrone anchored pH sensitive liposomes of doxorubicin
shown more cytotoxicity than free or non pH sensitive estrone
anchored liposomes. Side effects of doxorubicin such as
cardiotoxicity is reduced and less take up by kidney and higher
accumulation in tumour.
Impact of biomarkers in management of cancer

L-Asparaginase treatment of cancer guided by biomarker

 L-Asparaginase a bacterial enzyme used to treat lymphoblastic

leukaemia, selectively starve cells that cannot synthesise sufficient
asparaginase.
 For enhancing L-ASP activity by combining it with antagonists of
ASNS such as siRNAs, antisense nucleotides, antibodies or small
molecule inhibitors for treatment of cancer. Reducing or suppressing
the expression of ASNS potentiates the growth inhibitory activity of
L-ASP four to five-fold.

Personalized cancer vaccines

 There are several types of cancer vaccines which include nucleic

based, Mab- based and cell-based vaccines.

Personalized vaccines are:

1. Antigen specific vaccines

2. Tumour derived vaccines

3. FANG vaccine

4. My Vax

5. Onco Vax
Conclusion

 Personalized drug delivery system is most effective way to treat

cardiac arrhythmia and cancers

 It helps to avoid different side effects.

 It is customized for each person who is under treatment, it gives

treatment according to persons genetic makeup hence it is also called

as customised drug delivery system