What do we do when we have to revive a drying plant? Of course, we will have to water the roots of the plant regularly to make it back to its freshness. This could be a simple method to revive a drying plant, as directing water at the base of your plant delivers the hydration right where it’s needed: the roots. Similarly, the target delivery approach in healthcare would take the drugs directly to right where it’s needed: the disease site, icing apt treatment. We have put in our best effort to make it easily graspable what are the intracellular drug delivery technologies and how it can ensure effective treatment for fatal disease.
Below are the highlights that we feel would be helpful to understand about the intracellular drug delivery / intracellular non-viral drug delivery approach.
WHAT IS INTRACELLULAR DRUG DELIVERY?
Intracellular drug delivery system is used to deliver the genomic materials into specific cells to generate a therapeutic effect by correcting an existing abnormality or providing the cells with a new function. Another term used for intracellular drug delivery could be the cytosolic drug delivery approach, which requires lower overall amounts of drugs and minimizes unwanted off-target interactions in the intracellular space.
FOCUS ON NON-VIRAL DRUG DELIVERY
Non-viral drug delivery systems comprise all the physical and chemical systems except viral systems and generally include either chemical methods, such as cationic liposomes and polymers, or physical methods, such as gene gun, electroporation, particle bombardment, ultrasound utilization, and magnetofection. Efficiency of this system is less than viral systems in gene transduction, but their cost-effectiveness, availability, and more importantly less induction of immune system and no limitation in size of transgenic DNA compared with viral system have made them more effective for gene delivery than viral delivery systems.
NEED FOR NON-VIRAL DRUG DELIVERY
During our research we came across some of the major dot points why the healthcare sector is more inclined towards the non-viral drug delivery approaches. The main issues with viral delivery approach are the immunogenicity and cytotoxicity. An additional and concerning use of viral gene transfer vehicle is the phenomenon known as insertional mutagenesis which leads to ectopic chromosomal integration of viral DNA disrupts the expression of tumor suppression gene or activates oncogene leading to the malignant transformation of cells. Whereas the non-viral vectors have important safety advantage over viral approaches such as the reduced pathogenicity, low cost, ease of production and bio-safety properties. Hence, the Non-viral vectors have drawn significant attention due to its less immunotoxicity. Use of non-viral vectors in clinical trials increased from 2004 to 2013 while that of viral vector saw significant decrease.
MECHANISM OF INTRACELLULAR DRUG DELIVERY
As per our research, 44% nanoparticle-based vehicle are used for intracellular delivery approach followed by oligonucleotides (11%) and Cell Penetrating Peptides (CPP) (10%). However, we also witnessed few other vehicle types for intracellular drug delivery with diverse range of linkages for attachment of drugs for an efficient delivery. It is important to highlight that every molecule has different mechanism of intracellular delivery based on the type of diseases. Below we have presented a very generalised diagram portraying how the intracellular delivery actually works:
ROADBLOCKS TO HEADWAY
With pros comes the cons. Even through the non-viral drug delivery is meant suitable for different type of diseases, it still has to go long way to omit the drawbacks related to extracellular stability, extracellular stability (polynucleotide degradation in extracellular space), internalization (internalization of carrier), intracellular trafficking (endosomal rupture and polynucleotide release), nuclear entry (dissociation of polynucleotide from the carrier and entry of polynucleotide into the nucleus). Hence, it is evident that the improvements to increase the delivery efficiency are anticipated to grow at a higher pace providing a predictable long lasting, efficient and non-toxic delivery system in foreseen future.