I include gene delivery by polymeric nanoparticles.

1. POLYMERS CONTROLLED
DELIVERY OF THERAPEUTIC
NUCLEIC ACID
SIVASANGARI SHANMUGAM

2. CONTENT
• Polymers
• Types of polymers
• Uses
• Properties
• Polymeric nanoparticles
• Vehicle for gene delivery
• Delivery of therapeutic Nuclic Acid
 History
 Mechanism
 Polymeric release
 Substrate mediated delivery

3. POLYMERS
 The word comes from the Greek
words “Poly” means “Many” &
“Mers” means “Parts”.
 Polymers are complex & gaint
molecules usually with carbons
building the backbone,different
from the two molecular weight
compound.
 The small individual repeating
molecules are known as
monomers.
 A polymer with two different
monomers is known as a
Copolymer (or) Homopolymer.

5. USES OF POLMERS
• Polypropene finds usage in a broad range of industries such as textiles,
packaging, stationery, plastics, aircraft, construction, rope, toys, etc.
• Polystyrene is, actively used in the packaging industry. It is also used as an
insulator.
• The most important use of polyvinyl chloride is the manufacture of sewage
pipes. It is also used as an insulator in the electric cables.
• Polyvinyl chloride is used in clothing and furniture and has recently become
popular for the construction of doors and windows as well. It is also used in
vinyl flooring.
• Urea-formaldehyde resins are used for making adhesives, moulds, laminated
sheets, unbreakable containers, etc.

6. PROPERTIES OF POLYMER
Physical Properties :
1. As chain length and cross-linking increases the tensile strength of the
polymer increases.
2. Polymers do not melt, they change state from crystalline to semi-
crystalline.
Chemical Properties :
1. Compared to conventional molecules with different side molecules,
the polymer is enabled with hydrogen bonding and ionic bonding
resulting in better cross-linking strength.
2. Dipole-dipole bonding side chains enable the polymer for high
flexibility.
3. Polymers with Van dar waals forces linking chains are known to be
weak, but give the polymer a low melting point.

7. POLYMERIC NANOPARTICLES

8. POLYMERIC NANOPARTICLES
 PNPs are quickly expanding.
 Play an important role in wide spectrum of areas ranging from
Electronics, Medicines, Sensors, Biotechnology, Pollution controll
etc..,
 PNPs are vehicle for Drug delivery, Protein, DNA to target cells &
organs.

9. GENE DELIVER
• Gene delivery is a process of
introducing foreign genetic
material,such as DNA or
RNA,into host cells.
• Genetic material must reach the
nucleus of the host cell to induce
gene expression.

10. VEHICLE FOR GENE DELIVER
• Vehicles for gene delivery can be fabricated from both natural and synthetic
polymers and processed into a variety of forms, including :
1. NANOSPHERES
2. NANOCAPSULE
3. MICROSPHERES
4. SCAFFOLDS

11. NANOSPHERES
 Nanospheres are particles with diameters ranging from approximately 50
to 700 nm
 consistent with the size of viral and nonviral vectors. Nanoparticles are
internalized and release DNA intracellularly.

12. MICROSPHERES
 In contrast, microspheres, with diameters ranging from 2 to 100 μm, are
not readily internalized, but retained within the tissue to release DNA
 Released DNA can transfect cells at the delivery site, with the protein
product acting locally or distributed systemically

13. SCAFFOLDS
 Alternatively, polymeric scaffolds function to define a three-dimensional
space and can either be implanted or be designed to solidify upon
injection.
 These scaffolds can deliver DNA to cells within the surrounding tissue or
can target those cells infiltrating the scaffold.
 The scaffold can also distribute the vector throughout a three-
dimensional space, and transfection on a three-dimensional construct
may extend transgene expression

14. • retained within the
tissue to release
DNA
• scaffolds can deliver
DNA to cells within
the surrounding
tissue
• Nanocapsules are
system in which the
substance is confined
to a cavity surrounded
by a unique polymer
membrane.
• Nanospheres are
matrix system in
which the drug (or)
other substances
are basically and
uniformly.
NANOSPHERES NANOCAPSULES
MICROSPHERESAFFOLRD

15. DELIVERY OF THERAPEUTIC
NUCLEIC ACID
 Different types of
biocompatible nanoparticles
have been used to deliver
genes.
 PNPs deliver genes (or)
therapeutic proteins including
drug which can either be
dissolved (or) encapsulated
them forming & a nanocapsule
respectively.
 PNPs can also deliver protein
to the taegeted cells by
entrapping them with in
structure forming a
nanosphere.

16.  The delivered therapeutic proteins act by altering defective proteins
or genes in the patients cells.
 The size of the polymer nanoparticle could be turned to enable these
drugs & therapeutic proteins to fit in.
 PNPs like all nanoparticles are capable of regaining their size once
inside the cell through the physiological change in pH.
 PNPs can used for targeted delivery by surface modification, and
they allow the delivery of combined active material.

17. HISTORY
1. Mohammedi et al.have synthesized DNA chitosan nanoparticles to
deliver DNA to the lung epithelial cell.
2. Das et al. Have utilized PEI based nanoparticles to the siRNA to STAT3
in lung cancer invitro & invivo.
3. Other research group have also synthesized chitosan as a main
targeting nanoparticles for siRNA delivery to treate different disease
like lung cancer, ovarian cancer, pancreatic cancer, hapatocellular
carcinoma.
4. In 2015, Bishop et al. Have utilized polymer coated gold nanoparticles
for DNA & siRNA delivery.
5. Colombo et al. Have synthesized hybrid lipid-polymer nanoparticles for
siRNA delivering.

18. MECHANISMS
1. POLYMERIC RELEASE
2. SUBSTRATE
MEDIATED DELIVERY

20. POLYMERIC RELEASE
For polymeric release,
 DNA is entrapped within the material and released into the
environment, with release typically occurring through a combination of
diffusion and polymer degradation.
 Polymeric delivery may enhance gene transfer by first protecting DNA
from degradation and then maintaining the vector at effective
concentrations, extending the opportunity for internalization.
 DNA release into the tissue can occur rapidly, as in bolus delivery, or
extend over days to months.
 For rapid release, levels would be expected to rise quickly and decline as
the DNA is cleared or degraded.

21. SUBSTRATE MEDIATED DELIVERY
• The concentration may be maintained within an appropriate range by adjusting the release
to replace DNA that is cleared or degraded.
• Conversely, substrate-mediated delivery, also termed solid-phase delivery, describes the
immobilization of DNA to a biomaterial or extracellular matrix, which functions to support
cell adhesion as well as migration and places DNA directly in the cellular
microenvironment.
• The immobilization of DNA to the matrix may seem counterintuitive given the need for
cellular internalization to achieve expression; however, natural and synthetic corollaries
exist for growth factors and viral vectors.
• Growth factors associate with the extracellular matrix, functioning directly from the matrix
or upon release.
• In substrate-mediated delivery, DNA is concentrated at the delivery site and targeted to the
cells that are adhered to the substrate.
• Cells cultured on the substrate can internalize the DNA either directly from the surface or
by degrading the linkage between the vector and the material.

22.  Molecular interactions between the vector and the polymer ,whether the
DNA is bound to the delivery vehicle.
 Viral & nonviral vectorscontain negatively charged DNA/ RNA potentially
complexed with proteins, cationic polymers, interact with polymeric
biomaterials through nonspecific mechanisms, including hydrophobic,
electrostatic, and van der Waals interactions.
 These interactions have been well characterized for adsorption and
release of proteins from polymeric systems.
 Nonspecific binding depends upon the molecular composition of the
vector (e.g., lipid, polymer, protein) and the relative quantity of each (e.g.,
N/P).
 Alternatively, specific interactions can be introduced through
complementary functional groups on the vector and polymer, such as
antigen–antibody, to control vector binding to the substrate.

23.  The effective affinity of vector for polymer is determined by the
strength of these molecular interactions, which may also be influenced
by environmental conditions (e.g., ionic strength, pH), binding-induced
conformational changes, or vector unpacking.
 Delivery from most polymeric systems likely occurs through a
combination of binding and release mechanisms, and both the vector
and the polymer can be designed to regulate these interactions.
 A variety of natural and synthetic materials used for DNA delivery, which
can be either hydrophobic/ hydrophilic polymers.
 Hydrophobic - e.g., poly(lactide-co-glycolide) ,polyanhydrides
 hydrophilic polymers- e.g., hyaluronic acid (HA), collagen,
poly(ethylene glycol)

24.  Synthetic polymers such as PLG and polyanhydrides have been widely used in
drug delivery applications, as they are biocompatible and available in a range of
copolymer ratios to control their degradation
 Drug release from these polymers typically occurs through a combination of
surface desorption, drug diffusion, and polymer degradation
 For DNA delivery, polymer processing techniques are being developed to
fabricate a range of geometries and properties while retaining the activity of the
vector during processing and release.
 Alternatively, can be employed to process hydrophilic polymers into hydrogels.
These hydrogels are often more than 98% water and maintain the activity of
encapsulated vectors, which are released by diffusion from the polymer network.
 These hydrophilic polymers, along with some hydrophobic polymers, contain
functional groups (e.g., carboxylic acids, amines) in the polymer backbone that
can be readily modified, allowing interactions between the polymer and the
vector to be manipulated.

26. REFERENCE
1. https://byjus.com/jee/polymers/?utm_source=Google&utm_medium=cpc&utm_c
ampaign=K12-Traffic-DynamicSearch-
India&utm_term=&gclid=EAIaIQobChMIuL_3vPHR5AIVyxErCh1zCA24EAAYASAAEgL
KqvD_BwE
2. https://www.sigmaaldrich.com/technical-documents/articles/material-
matters/delivery-of-nucleic-acids-using-polymers.html
3. https://www.semanticscholar.org/paper/Bioresponsive-polymers-for-the-delivery-
of-nucleic-Edinger-Wagner/2f42d1290d661bd7423b70912242030cbf9f96bc
4. https://www.cell.com/action/showPdf?pii=S1525-0016%2804%2900123-6

27. THANK YOU