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New Polymeric Carriers on Cancer Treatment

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Sahil Bangar

on 25 February 2014

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Transcript of New Polymeric Carriers on Cancer Treatment

New Polymeric Carriers on Cancer Treatment
New Polymeric Carriers on Cancer Treatment
Overview
Objective
Current Cancer Treatments and their Disadvantages
Polymer as novel Drug Deliver Carrier
Nanosphers/Microspheres - A potential Drug delivery carrier
Recent Progress
Recommendation and Conclusion
Objective
Cancer Treatments and their Disadvantages
Polymer as Novel Drug Delivery Carrier
Jennifer Polland, This Nanoparticle System May Lead To A Cure For Cancer, http://www.businessinsider.com/nanoparticle-system-may-cure-cancer-2012-7?op=1#ixzz2tv2BECC4, Accessed Feb 20, 2014
Disadvantages of Current Treatments
Not everyone can undergo it
Not all tumors are operable
Instructor: Dr. R. Narain

Group Members:
Ankit Kumar
Susan Romero
To demonstrate importance of finding new cancer drug delivery carrier for fighting cancer which is the leading cause of death in Canada and world
In 2012 14.1 million new cancer cases
8.2 million deaths in world
To research current cancer drug delivery methods
To suggest improvement in current drug delivery methods in order to create drug carriers that are more effective and efficient

Current Treatments
Surgery
Chemotherapy
Radiation
Targeted therapy
Immunotherapy
Transplantation: bone marrow, peripheral blood and cord blood transplant
Others: angiogenesis inhibitors, biological therapies, vaccines, cryosurgery, hyperthermia, laser, photodynamic

Surgery
Types of Polymeric Carriers
Properties and Benefits of Relevant Polymers
Properties
Biodegradable
Bio compatible
Common examples: Poly(lactic-co-glycolic) acid (PLGA), Polycaprolactone (PCL), and amino acids
Benefits
Controlled release of drugs
Specific targeting to cancerous cells (high efficacy, low toxicity)
No subsequent removal treatment
Can be modified depending upon requirements
Therapeutic effectiveness and side effects reduction

Nanospheres/ Microspheres as Drug Delivery Carrier
Why Nanospheres/Microspheres?
Benefits
Easy large scale production
Large loading capacity
Better protection of encapsulated drug from external milieu

Drawback
Concerns over toxicity because of use of surfactants during synthesis

Nanosphere/ Microsphere Synthesis
Emulsion solvent evaporation technique
Emulsion cross linking method
Coacervation method
Spray drying technique
Emulsion-solvent diffusion technique
Multiple emulsion method
Ionic gelation

Prasanth VV, Akash Chakraborthy Moy, Sam T Mathew, Rinku Mathapan, Microspheres - An Overview. International,
Journal of Research in Pharmaceutical and Biomedical Sciences, 2 (2), 2011, 1242-1254.
Preparation of Nanospheres/Microspheres by Solvent Evaporation
P.B. O’Donnell, J.W. McGinity / Advanced Drug Delivery Reviews 28 (1997) 25 –42
Recent Progress
Preparation and Characterization of Anticancer Drug-Loaded Implantable PLGA Microparticles
Aim of study: to prepare and physicochemically characterize Doxorubicin (DOX)-loaded PLGA
Microparticles, could be directly injected into the tumorous brain tissues
PLGA microparticles prepared by using a modified version of an o/w single-emulsion solvent evaporation process.
Organic phase consists of PLGA polymer in an acetone-dichloromethane mixture (0.5:1)

DOX release profile is obtained in PBS, pH 7.4
Release study carried out in sink conditions.
Cumulative in vitro release of DOX from PLGA microparticles shown in Figure below
From graph, initial release of DOX (60% of the DOX) fast
Poorly entrapped in the polymer matrix during first day
Novel Technique to Decrease Release Time
With PLGA hollow microspheres (HMs), delivery of anticancer drug into tumor cells and quick release of drug in acidic organelle
Sodium bicarbonate (NaHCO3) incorporated, while preparation of hollow microsphere via water-in-oil-in-water (W/O/W) double-emulsion, solvent-diffusion–evaporation technique
In acidic environment such as near lysosome NaHCO3 reacts to generate Carbon dioxide bubbles, producing bursting of walls of the Microsphere helping release the anticancer drug to the targeted organ
Doxorubicin (DOX) as an example of an anticancer drug, because it has fluorescence capability
DOX was encapsulated in the aqueous core of HMs by physical means, as opposed to covalent attachment
To help track the particles intracellularly, PLGA shells of HMs were doped with DiO, a lipophilic dye

Novel Technique
Schematic structural representation of a PLGA hollow microsphere containing doxorubicin and the release mechanism of drug

Recommendation and Conclusion
Recommendations for Use of pH
Sensitive Polymers
pH sensitive or responsive polymers are cross-linked which respond to the changes in the pH of the surrounding medium
Such materials increase its size (swell) or collapse depending on the pH of their environment
This responsiveness is exhibited due to the presence of certain functional groups in the polymer chain
The extent of swelling will depend on the quality of solvent, ionization degree, crosslink density, and ionic strength
pH-Sensitive Polymers Classification
1. Anionic pH sensitive polymers: contain acidic functional group like carboxylic acid.
Examples: Poly alkyl acrylic acids and their copolymers with other hydrophobic polymers (Poly acrylic acid (PAA)–co-Poly methyl methacrylate (PMMA), Poly (styrene-alt-maleic anhydride) (PSMA).





2. Cationic pH sensitive polymers: contain basic functional groups like amino group.
Examples: Polyethyleneimine, Poly (L-lysine), Poly (b-amino esters), Chitosan


Chitosan a polysaccharide & polycationic polymer derived from chitin (βlinked N-acetyl- D-glucosamine) by partial N-deacetylation and hydrolysis
It has primary and secondary hydroxyl group & free amino group
With a pKa of approximately 6.5, chitosan is soluble in acidic solutions owing to the protonation of the amino groups composing the polymeric chain at this pH.
Chemical/IUPAC name: Poly-(1-4)-2-Amino-2-deoxy-ß-D-Glucan
Molecular weights: LMW: 40000 Da; MMW: 480000 & HMW: 850000 Da
Chemical Structure:
Proposed Polymer
Conclusion
Use of pH sensitive cationic polymer along wih the use of sodium bi carbonate could decrease the release time even further thus having another control on release behavior
Overall, use of polymers in cancer drug delivery is very promising
Polymeric carriers increase efficiency and safety of the drug
Few drawbacks involves like toxicity issues, difficult synthesis process and delivery to a specific tissue, which require extensive research to make it a commercial cancer drug delivery treatment method
Chemotherapy
Damage to healthy cells
Side effects: bleeding, nervous system changes, diarrhea, hair loss, infection, etc.
Radiation Therapy
Treats tumor in specific areas: not broad
Side effects: fatigue, skin changes, and others depending on the area treated
Kevin Letchford, Helen Burt, European Journal of Pharmaceutics and Biopharmaceutics 65 (2007) 259–269
Cetin, M.; Vural, I.; Atila, A.; Kadioglu, Y.. Preparation and characterization of anticancer drug-loaded implantable PLGA microparticles. Turkish J. Chem. 2010, 34, 509-516
Cetin, M.; Vural, I.; Atila, A.; Kadioglu, Y.. Preparation and characterization of anticancer drug-loaded implantable PLGA microparticles. Turkish J. Chem. 2010, 34, 509-516
Cherng-Jyh Ke, Tzu-Yuan Su, Hsin-Lung Chen, Hao-Li Liu, Wei-Lun Chiang, Po-Chun Chu, Younan Xia, and Hsing-Wen Sung, Smart Multifunctional Hollow
Microspheres for the Quick Release of Drugs in Intracellular Lysosomal Compartments. Angew. Chem. Int. Ed. Engl. 2011, 50, 8086–9.
Cherng-Jyh Ke, Tzu-Yuan Su, Hsin-Lung Chen, Hao-Li Liu, Wei-Lun Chiang, Po-Chun Chu, Younan Xia, and Hsing-Wen Sung, Smart Multifunctional Hollow Microspheres for the Quick Release of Drugs in Intracellular Lysosomal Compartments. Angew. Chem. Int. Ed. Engl. 2011, 50, 8086–9.
Cherng-Jyh Ke, Tzu-Yuan Su, Hsin-Lung Chen, Hao-Li Liu, Wei-Lun Chiang, Po-Chun Chu, Younan Xia, and Hsing-Wen Sung, Smart Multifunctional Hollow Microspheres for the Quick Release of Drugs in Intracellular Lysosomal Compartments. Angew. Chem. Int. Ed. Engl. 2011, 50, 8086–9.
Cherng-Jyh Ke, Tzu-Yuan Su, Hsin-Lung Chen, Hao-Li Liu, Wei-Lun Chiang, Po-Chun Chu, Younan Xia, and Hsing-Wen Sung, Smart Multifunctional Hollow Microspheres for the Quick Release of Drugs in Intracellular Lysosomal Compartments. Angew. Chem. Int. Ed. Engl. 2011, 50, 8086–9.
Saunders, B. R.; Vincent, B. Microgel Particles as Model Colloids : Theory , Properties and Applications. Adv. Colloid Interface Sci. 1999, 1–25.
Grainger, S.; El-Sayed, M. Stimuli-Sensitive Particles for Drug Delivery; 2010; pp. 171–190.
Grainger, S.; El-Sayed, M. Stimuli-Sensitive Particles for Drug Delivery; 2010; pp. 171–190.
Picture source: Plain surface melamine nanospheres and microspheres
http://microspheres-nanospheres.com/Microspheres/Organic/Melamine/melamine.htm
Picture source: Treatment Options, http://www.millenniumphysicians.com/cancer-treatments/, Accessed Feb 20, 2014.
Source:http://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:16261
Davis, S. P., Chitosan : manufacture, properties, and usage. In: Biotechnology in Agriculture, Industry and Medicine. Hauppauge, N.Y. : Nova Science Publishers. 2011. eBook. , Database: eBook Collectio (EBSCOhost)
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