B.

PHARM FOURTH YEAR (SEMESTER VIII)

DRUG DELIVERY SYSTEMS (TUTORIAL I)
Name: SONU LAXMAN SHARMA
Roll no: B050

Gene delivery using nanocarriers

Gene therapy is a technique in which faulty genes are corrected to cure gene
associated diseases such as thalassemia, sickle cell anemia, cystic fibrosis, Tay-
Sachs disease etc. by changing how the gene express themselves in the cells of the
patient .Nanocarriers have been a promising drug delivery vehicles for many
researchers due to its ability to reach areas where standard drug delivery systems
fails to reach. Furthermore, they provide site specificity which is critical in gene
therapy. Nonspecific adsorption and aggregation in physiological fluids are 2 of
the most serious problems from clinical point of view. There are 2 types of gene
therapy In Vivo and Ex vivo. In In Vivo gene therapy the genes are introduced
directly into the patient cells while the cells are still in patients body whereas in Ex
vivo gene therapy the cells are removed from the patients body then the genes are
added to those cells in the lab and the cells are then returned to those patients.

Challenges faced during Clinical trials

(1) Biodegradation & Biocompatibility.

(2) Aggregation in physiological fluids.
(3) Nonspecific adsorption by non-desired tissues.
(4) Cellular endocytosis
(5) Clearance in circulation
(6) Adverse effects and high cost.
Strategies adopted to overcome the above challenges

(1) PEGylation of nanocarriers improves stability and circulation time and

prevents absorption.
(2) Specific ligand receptor-mediated active targeting. (Improves gene target
efficacy in vivo)
(3) Passive targeting.

Research and advancement in this field

Cheng et al developed a series of cationic helical polypeptides to deal with the

efficiency toxicity poor correlation with normal carriers by using natural polymers
such as cyclodextrins, chitosan, and many other low molecular weight polymers.
Furthermore, these polymers help in overcoming the challenges such as
biocompatibility and biodegradation. They mainly worked on CALLA-01, a
targeted nanoparticle system based on cyclodextrins which went through human
phase-1 clinical trial.

Davis et al also worked on CALLA-01 and reported a phase 1 clinical trial against
cancers. Their results demonstrated that this drug could deliver siRNA to
melanoma cells by systemic administration and can show effective anticancer
activity against various types of cancer.

Conclusion

Gene therapy using nanocarriers has a come a long way since these past decade ,
but due to some of the challenges faced by this technique it raises a question about
its safety and affordability to the consumer . With further advancement in
nanotechnology this technique can be a promising technique for treating gene
associated diseases .