Chemistry
2. The nano carrier needs to remain in suspension in H2O, PBS, human serum, etc. What type of polymer do you need to use to decorate the surface of the nanocarrier to achieve this goal?
In order to maintain the nanocarrier in suspension in water, Phosphate-Buffered Saline (PBS), human serum a suitable solution a polymer is needed on its surface. The polymer used needs to accomplish three goals. The polymer needs to decorate the nanocarrier surface to enhance suspension and secondly, to prevent protein absorption. Another characteristic is that the polymer evades the immune system. PLGA poly(lactic-co-)glycolic acid is the polymer.
3. Chemical structures
Figure 1Chemical Structure for PEG (Ju, 2015) A component of PLGA
The chemical structure of PEG shows a single-strand organic polymer. (See fig.1) ‘n’ denotes the site where higher numbers of the same single-strand organic polymer are able to produce a chain.
Figure 2 Chemical Structure for PLGA and the products of a hydrolysis reaction
(Makadia & Siegel, 2011).
4. Most important configurations to reduce protein adsorption
The reason is because the polymer remains on the nanocarrier surface by covalent attachment and the most recent knowledge on the interactions indicate a reduction of protein adsorption (Schottler et al., 2016). The capability of protein absorbance reduction is called “the stealth effect” (Schottler et al., 2016). The most important configuration of the polymer for protein reduction appears to be PGLA copolymers because they are able to block ‘foreign’ molecules and prevent reactions, and protein is therefore reduced. (On the other hand, the drug being delivered also consists of ‘foreign’ molecules so the ideal balance must be reached if applying PLGA copolymers.)
5. Monomer ratio (X:Y) for nanocarrier synthesized with PLGA
The ratio for lactic acid to glycolic acid for a copolymer synthesized with a nanocarrier can be 50:50 (50% lactic acid to 50% glycolic acid), 65:35, 75:25, and 85:15 (Makadia & Siegel, 2011).
6. Would you use an amorphous or crystal PLGA polymer or a mixture or both to synthesize your nanocarrier?
PLGA has a proven track record for use as a drug delivery system so PLGA would be my choice. PEG displays a crystalline structure versus an amorphous, more soluble configuration. The properties are suitable for using with drugs that are stable with Tg (°C) = 45 to 55. The degradation rate of PGLA is slower than the PGA crystalline structured polymer of 2-3 months. The degradation for PLA (D, L form) amorphous polymer exhibits a degradation rate from 12-15 months, PLGA exhibits a degradation rate of one to six months and one of its typical applications is for drug delivery at the microsphere level.
7. Which configurations does your nanocarrier need to reduce protein adsorption and evade the immune system?
Lactic and glycolic acid
( the IUPAC name PGLa (peptidyl-glycylleucine-carboxyamide) Poly(lactic-co-glycolic acid) (PLGA
surface
The functional unit of the PEG component of the molecule is the hydroxyl, OH¯. (See fig. 1) PEG is the basic component from which block co-polymers are built in an effort to develop more effective drug delivery systems. DSPE-PEG (with an amine) and COOH-PEG (acetic acid ether also designated as -R) polymers are useful in self-assembly activities (Al-Jamal et al.). The functional groups present in the structure are NH3, amine and COOH¯, acetic acid ether. Poly lactic-co-glycolic acid (PLGA) is another polymer with high potential to enhance drug delivery of nanocarrier.
The oxygen molecule binds with the oxygen of the hydroxyl group and the carbon of the carboxyl group. During the drug delivery the drug is in encapsulated form so it cannot react during hydrolysis (or other reactions) that may be present. Another positive aspect for PLGA nanoparticles (or microspheres) is their multi-functionality. When the nanocarrier is used as a health deliver tool, the side effects from the drug are reduced because the drug can be administered in encapsulated form (Makadia & Siegel, 2011).
8. What will be the size of the designed nanocarrier? specific size, charge relation to the therapeutic effectiveness of the nanocarrier
The size and surface charge of the polymeric nanoparticles are the main factors for activating the complement system. The surface charge is linked to the main proteins in the complement system. The PLGA is designed for self assembly and is composed of
diameter 120μm
Molecular weight: 50:50 PLGA density 1.34 g/cm2 amorphous Charge -25 2004
9. Draw the shape of the designed nanocarrier and explain the elements that form it.
Lactic acid is a poly-acetic acid is hydrophilic (water-loving) because of the COOH (or-R group, also known as the carboxyl group). Lactic acid is a very weak acid compared to acetic acid (which is also a weak acid); but the Pka for lactic acid is less and the pH is only about 2.4 to 3.8; the Normality is only 0.1 N. As the polymer’s surface erodes due to hydrolysis the carboxylic groups (which are hydrophilic) increase, but at the same time the molecular weight decreases. (MW of lactic acid is 90.08 g/mol). The lactate ion is CH3CH(OH)CO2− the OH¯ is the hydroxyl group and the carboxyl group is O=CH3CH(OH); the double bond to the oxygen molecule is between the methyl group (CH3) of the carboxyl acid and the hydroxyl group. (See the figures)
10. Write the X = hydrophobic Y = hydrophilic
Y-Y-Y
The stealth effect is due to the same properties that have been seen to enhance the drug delivery efficacy of nanocarrier (Slamaso and Caliceti, 2013).
11. What if nanocarrier is not designed well where in the body do they end up?
The problems that can occur with poorly designed nanoparticles is when the nanoparticles enter into reactions with molecules in the living organism (the human body). Proteins coating the nanocarrier can potentially reduce the body’s immune defense system. plaques can be created within the cell and intensify certain diseases like amyloid disease. Nanoparticles can potentially move from the inside the nose’s upper lining into the brain.
12. If the complement is activated in the presence of the nanocarrier will reach the target tissue
Yes because proteins activated with the complement make the nanocarrier more effective at reaching the target area. Yes, the nano carrier will reach the targeted system if the complement system is activated, because the proteins will make the movement of the nanocarriers more efficient. C1q3 and C3b3 can bind to the nanocarrier surface and one CLq is 3 polypeptide chains. They are homologous and cause binding to target tissues.
13. If the drug delivery system is administered subcutaneous do you think that the complement system will be activated?
Subcutaneous delivery can activate the complement system if the “stealth liposomes;” liposomes with PEG are present. PEG on the surface of liposomes enhances the delivery to target tissues. liposoids are in the same class as other colloidal particulates such as the microspheres and nano-carriers as well as the reverse micelles.
17. Once you have synthesized your nano carrier would you use to characterize it? SEM or TEM
(See fig. 2) Hydrolysis is a main type of degradation mechanism and the reaction I would choose. The polymer is degraded during hydrolysis into its basic monomers while water is consumed (used during the reaction). The nanocarrier is large so I would use the TEM (Transmission electron microscopy). The scanning electronic microscope
18. what is the source of energy in the SEM and TEM electron
The SEM scans the sample with scattered electrons and the source of energy is a low energy electron beam
The TEM uses transmission of an electric beam that passes through the sample
SEM is less damaging to samples.
19. What type of info does SEM and TEM give about the sample
Electron microscopes can show cells, bacteria and viruses, macro molecule and small molecules.
The SEM scans the surface of a sample so it gives info about the topography (texture, etc.), the shape and size of particles and the crystallographic arrangements of atoms.
The TEM is able to display more detailed information because the strong electronic beam allows a snapshot of a cross section of the sample. The TEM is used to study cancer cells, viruses, and nanotechnology.
Erosion process.
use the 50:50 line
PLGA has properties of biodegradability that is a controlled drug deliver carrier.” PLGA-PEG copolymers have been found to be effective when develop into diblocks (PLGA-PGA) and as triblocks with the ABA or BAB configurations. The ABA is configured as PLGA-PEG-PLGA and the BAB is PEG-PLGA-PEG.
References
Gref, R., Domb, A., Quellec, P., Blunk, T., Müller, R. H., Verbavatz, J. M., & Langer, R. (1995). The controlled intravenous delivery of drugs using PEG-coated sterically stabilized nanospheres. Advanced Drug Delivery Reviews,16(2-3), 215–233. http://doi.org/10.1016/0169-409X(95)00026-4
Ju. (2015). PEG Structural Fomula V1. By Jü - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=38464529
J. Kahovec, R. B. Fox and K. Hatada (2002). "Nomenclature of regular single-strand organic polymers". Pure and Applied Chemistry 74 (10): 1921–1956. doi:10.1351/pac200274101921
Makadia, H. K., & Siegel, S. J. (2011). Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier. Polymers, 3(3), 1377–1397. http://doi.org/10.3390/polym3031377
Stefano Salmaso and Paolo Caliceti, “Stealth Properties to Improve Therapeutic Efficacy of Drug Nanocarriers,”Journal of Drug Delivery, vol. 2013, Article ID 374252, 19 pages, 2013. doi:10.1155/2013/374252
Susanne Schöttler, Greta Becker, Svenja Winzen, Tobias Steinbach, Kristin Mohr, Katharina Landfester, Volker Mailänder & Frederik R. Wurm. (2016),Protein adsorption is required for stealth effect of poly(ethylene glycol)- and poly(phosphoester)-coated nanocarriers. Nature Nanotechnology, doi:10.1038/nnano.2015.330
