Polymers controlled delivery of therapeutic nucleic acid

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 .

4. 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.

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

6. POLYMERIC NANOPARTICLES

7. 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.

8. 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 .

9. 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 : NANOSPHERES NANOCAPSULE MICROSPHERES SCAFFOLDS

10. 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 .

11. 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

12. 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

13. 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 .

14. 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.

15. HISTORY Mohammedi et al.have synthesized DNA chitosan nanoparticles to deliver DNA to the lung epithelial cell. Das et al. Have utilized PEI based nanoparticles to the siRNA to STAT3 in lung cancer invitro & invivo . 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. In 2015, Bishop et al. Have utilized polymer coated gold nanoparticles for DNA & siRNA delivery. Colombo et al. Have synthesized hybrid lipid-polymer nanoparticles for siRNA delivering .

16. MECHANISMS POLYMERIC RELEASE SUBSTRATE MEDIATED DELIVERY

17. 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.

18. 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.

19. 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.

20. 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)

21. 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.

22. REFERENCE https://byjus.com/jee/polymers/?utm_source=Google&utm_medium=cpc&utm_campaign=K12-Traffic-DynamicSearch- India&utm_term=&gclid=EAIaIQobChMIuL_3vPHR5AIVyxErCh1zCA24EAAYASAAEgLKqvD_BwE https://www.sigmaaldrich.com/technical-documents/articles/material-matters/delivery-of-nucleic-acids-using-polymers.html https://www.semanticscholar.org/paper/Bioresponsive-polymers-for-the-delivery-of-nucleic-Edinger-Wagner/2f42d1290d661bd7423b70912242030cbf9f96bc https://www.cell.com/action/showPdf?pii=S1525-0016%2804%2900123-6

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