Thursday, June 7, 2012

Week 9 & 10

Final Design/Novel Application


  • Nanoparticles of albumin and cancer medication matrixed with microbbuble w/PLA and anti-CD47
  • Modeling Microbubble Jetting

Project Presentation:

Held on Wednesday, June 6th, 2012 at 3:30pm (Curtis 162 - MEM)

Project Final Report:

Due Friday, June 8th, 2012
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Monday, May 28, 2012

Week 7 & 8


 Criteria on Evaluating Alternative Solutions:

  1. Cost
  2. Effectiveness/Efficacy 
  3. Biocompatibility 
  4. Biodegradability 
  5. Ease of Use 
  6. Safety
  7. Time Active in System  
  8. Time Present in System  
  9. Ease of Access

Weighting Formula: 


Weighting Formula
Cost
Effectiveness
Biocompatibility
Biodegradability
Total=100%
15%
20%
10%
5%
Details on Each Criteria
Cost of procedure to make the materials (drug, etc.) used in the procedure; Cost to store them; Cost of the input (syringes, machinery). The solution with the lowest cost will have the highest ranking.
How effective the drug is as well as the procedure to deliver the drug
Are there any reactions/side effects affecting the body due to the drug?
Is the drug harmful when treated in the body? Any radioactivity?
  
Ease of Use
Safety
Time active in system
Time present in system
Ease of Access
5%
20%
15%
5%
5%
Is there specific instruments or medical equipment, such as UV fluids, syringes, machinery, that will be utilized for the procedure?
Safety is an important factor in determining whether the solution is viable for general use or only for certain demographics.
How the long the drug can be activated to work and how long the drug actually works
How long the microbubbles and drugs stay in the system that is inactive to the primary purpose
Does it require special containers to store and transfer, such as temperature- or radiation-sensitive containers?

Criteria Evaluation:

 
Criteria Evaluation (Out of 5.0):
1 (least favorable)
3 (moderately favorable)
5 (most favorable)


Alternative Solutions
Cost (15%)
Effectiveness (20%)
Biocompatibility (10%)
Biodegradability (5%)
Ease of Use (5%)
1) Adjust the number and positioning of the microbubbles in order to rupture the capsule
5
3
4
3
4
2) Incorporate antibodies throughout the polymer shell of microbubbles
3
3
3
3
4
3) Composite materials for coating the microbubbles
2
2
4
3
2
4) Use of Polylactic Acid
3
3
4
3
3
5) Albumin and other drugs cross linked with microbubbles
4
4
4
2
4
6) Liposomes and Microbubbles together
3
3
4
3
4






Alternative Solutions
Safety (20%)
Time active in system (15%)
Time present in system (5%)
Ease of Access (5%)
Total Weighted Score Out of 5.0
1) Adjust the number and positioning of the microbubbles in order to rupture the capsule
3
3
3
3
3.45
2) Incorporate antibodies throughout the polymer shell of microbubbles
4
2
2
3
3.05
3) Composite materials for coating the microbubbles
4
4
3
3
3.05
4) Use of Polylactic Acid
4
4
3
3
3.45
5) Albumin and other drugs cross linked with microbubbles
4
4
3
4
3.85
(most favorable)
6) Liposomes and Microbubbles together
2
4
3
2
3.05



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Thursday, May 10, 2012

Week 5 & 6

Alternative Solutions to Further Assess and Evaluate:

1.     Adjust the number and positioning of the microbubbles in order to rupture the capsule

  • One of the main problems with using a polymer shell as a transport vehicle for drugs is that scientists have been unable to rupture the capsule by microbubble cavitation. Existing research has demonstrated that microbubble cavitations near solid walls generate jets of water in the direction of the wall. This results from the pressure difference on each side of the microbubble. By varying the number and location of microbubbles along with the above principle, it may be possible to concentrate the force on a specific area to break through the polymer shell.       

2.     Incorporate antibodies throughout the polymer shell of microbubbles 

  • The advantage of antibodies on the polymer coating is that this would help the microbubbles to stick and attach to the targeted designated site more efficiently, such as a cancer tumor. It would also weaken the microbubble shell so that it will be able to be ruptured easily using ultrasound and release the medicine that are inside the microbubbles. Research has been done in analyzing the attachment of specific antibodies to the phosphatidylserine (PS) layer of Sonozoid (which consists of perfluorobutane gas microbubbles stabilized by a membrane of hydrogenated egg phosphatidylserine). The attachment of antibodies was used to detect the PS layer specifically for “targeted molecular imaging”. However, this has not been implemented in the process of actual drug delivery. 
  • Phosphatidylserine (PS) exists and is exposed on the outer membrane of cells during the apoptosis stage, or the cell death stage. PS also has been found on cancer cells, which ironically prevents the death of these cells. As a probable solution, the idea of having microbubbles covered with specific antibodies or contrasting agents would be used to detect and attach to the PS layer of cancer tumor cells, instead of the microbubbles being covered by PS. This would eventually help in safely and directly releasing the medicine into the cancer cell, as the microbubbles are ruptured by the ultrasound. In the study mentioned above, the possible antibodies or agents that was utilized on Sonozoid were Fluorescein-Labeled Annexin V, PE-streptavidin with PE Biotinylated Annexin V (Avidin-Biotin binding), or the Avidin -Biotin binding along with a biotinylated Alexa488–IgG antibody. These antibodies/agents may be suitable for a new design of polymer-covered microbubbles, if they are sufficiently effective, do not cause any side effects in the body, and if it is not costly to be developed. It may also be convenient if the microbubbles had a phospholipid bilayer with PS already on its membrane. 
  • http://search.proquest.com/biologicalscience/docview/855954465/1368E50A5FB1528C1FD/6?accountid=10559

3.     Composite materials for coating the microbubbles

  • Magnetic/PLA composite microbubble with various structures and controllable average size can be prepared by a modified double emulsion solvent evaporation.  Certain amount of manganese phosphide  and pla are mixed and dissolved in dichloromethane. Then 2-3 milliliters of deionized water is added. The obtained emulsion is then poured into poly vinyl alcohol solution and homogenized for a certain amount of time. The resultant double emulsion is then stirred with 2% isopropanol solution and after waiting for couple of hours, the resultant microbubbles can be obtained. 
  • http://www.springerlink.com/content/h0831787r1n35838/fulltext.html#Sch1

4.     Polylactic Acid

  • Nowadays, some protein especially albumin based microbubbles are being used commercially for drug delivery. But polymeric microbubbles have some advantages over albumin based one. Since polymeric shells are thick and sturdy, it can possess a higher loading capacity. It is also stable and flexible. For this purpose, polylactic acid or PLA can be used to make microbubbles. This is also a biodegradable and biocompatible polymer. Another great advantage of PLA is the bubbles can be stored inside the polymeric shell for quite a long time and both hydrophobic and hydrophilic drugs can be incorporated.

5.     Albumin and other drugs cross linked with microbubbles

  • Albumin chosen as nanomaterial not only has some benefits as mentioned previously but also was easy to link to the protein ultrasound microbubbles for the purpose of targeting.There are two different methods for nanoparticles to carry genes. One of them is the single-step method, in which a gene is added to the albumin solution before the nanoparticles are prepared, and the gene DNA is encapsulated in the matrix of the nanoparticles. This method has some advantages because of the higher concentration of the drug, delayed and controllable release, enzyme resistance, and a longer time to transfect the gene. Another method is the two-step method, in which the albumin nanoparticles are prepared before the gene is added, and the pH value of the solution is adjusted to be acidic, which makes a more positive charge on the surface of the nanoparticles and links easily to the gene DNA with the negative charge. The nanoparticles made this way are equal in size, and the particle diameter is changed easily but without the advantages mentioned previously Albumin can be crosslinked to another protein by glutaraldehyde.The microbubbles carried with albumin nano-tPa plasmid could not escape from blood in the circulation because of their size (2–5 μm in diameter).
  • For breast cancer:
    • Several drugs that interfere with estrogen binding to the ER has been approved by the FDA for the treatment of ER-positive breast cancer. Drugs called selective estrogen receptor modulators (SERMs), including tamoxifen and toremifene (Fareston®), bind to the ER and prevent estrogen binding. Another drug, fulvestrant (Faslodex®), bind to the ER and promotes its destruction, thereby reducing ER levels inside cells.

6.     Liposomes and Microbubbles together

  • Microbubble shell is comparatively thin and thus has limited drug carrying capacity. An alternative solution would be the conjugation of microbubbles with the liposomes.
  • http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2662343/
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