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• Presented to: Dr. Javed AliPresented by: Shakeeb Ahmed
Jamia Hamdard
BIODEGRADABLE POLYMERIC DELIVERY
SYSTEM
BIODEGRADABLE POLYMERS
Nature’s way:
“Every resource made by nature returns to nature”
HO
W LO
NG
DO
ES IT TAK
E?
POLYMERIC MATERIAL DEGRADATION TIME
Cotton rags 1-5 months
Paper 2-5 months
Rope 3-14 months
Orange peels 6 months
Wool socks 1 to 5 years
Cigarette butts 1 to 12 years
Plastic coated paper milk cartons 5 years
Plastic bags 10 to 20 years
Nylon fabric 30 to 40 years
Aluminum cans 80 to 100 years
Plastic 6-pack holder rings 450 years
Glass bottles 1 million years
Plastic bottles May be never
HISTORY
• When polymers were synthesized from glycolic acid in 1920s, at that time, polymer degradation was viewed negatively as a process, where properties and performance deteriorated with time.
BIODEGRADABLE POLYMER: DEFINITION
• “Polymers that degraded/eroded by enzymes introduced in vivo or surrounding living cells or
• Degraded/eroded by non enzymatic process into oligomers ,after their intended purpose to result in natural byproducts (gases : CO2, N2; water, biomass, and inorganic salts)”
• Byproducts are metabolized and removed from the body via normal metabolic pathways.
ADVANTAGES
Less toxic compared to non-biodegradable polymers
Much higher doses of the drug can be delivered locally
Controlled drug release from the formulation
Stabilization of drug
Localized delivery of drug
Decrease in dosing frequency
Reduce side effects
Improved patient compliance
Polymer retain its characteristics till the depletion of drug
BIODEGRADABLE POLYMERS: classification
A: BASED ON ORIGIN Natural origin : Collagen, Albumin, Casein, etc. Semi-synthetic polymers : Gelatin, Dextran , Chitin, Alginate, Chitosan , etc. Synthetic polymers : Aliphatic polyesters : PGA, PLA,PCL, etc. Polyphosphoesters , polyanhydrides , polyphosphazenes, polyaminoacidsB. BASED ON ENVIORNMENTAL FACTORS: Thermosensitive polymer: Polyacrylamide , etc. Electrically and chemically controlled: Poly(pyrrole), collagen, etc. pH sensitive polymer: poly (2-ethylacrylic acid), etc.
C. MISCELLANEOUS: Polymeric phospholipids, Polyethyleneamine, Polyamidoamine, PEG
DIFFERENT MECHANISMS OF DEGRADATION
1. Chemical degradation
2. Physical degradation
3. Enzymatic degradation
ENZYMATIC OR CHEMICAL DEGRADATION
• Chemical or enzymatic degradation–mediated by water, enzymes, microorganisms.
CLEAVAGE OF CROSSLINKS
TRANSFORMATION OF SIDE CHAINS
CLEAVAGE OF BACKBONE
BIODEGRADABLE POLYMERS
• Acetal:
Hemiacetal:
• Ether
• Nitrile
• Phosphonate
• Polycyanocrylate
OH2
+C
O
H H
R' OHO C O
H
H
R R' R OH +
OC
C
C C
C
OH
OH
OH
OH
OH OHC
C
C C
OH
OH
OH
OH
H2O+
C==O
H
H2O
R C O C R'
H H
H H
OH2
R C OH
H
H
R' C OH
H
H
+
R C R
C N
H
R C R
C O
H
NH2
R C R
C O
H
OH
OH2 OH2
RO P OR'
O
OR''
OH P OH
O
OR''
OH2
+ +R OH OH R'
R C C C C R'
CN
C
OR''
CNH
HO C
OR'''
O
H
H
OH2R C C C
CN
C
OR''
H
HO
H
H
OH C R'
CN
C
OR'''
O
+
1) Bulk erosion
• Degradation takes place throughout
the whole of the sample.
• Water intake is faster than the polymerchain scission
• Eg : polyesters, PLA, PLGA, polylactones, poly(amino acids), and polyphosphazenes
2) Surface erosion
– Sample is eroded from the surface.
– polymer degradation is much faster
than water intake
– E.g. Polyanhydrides, polyorthoesters11
PHYSICAL DEGRADATION
METHODS OF STUDYING POLYMER DEGRADATION
• Morphological changes (swelling, deformation, bubbling, disappearance)
• Weight loss
• Thermal behavior changes (DSC)
• Molecular weight changes
– Size exclusion chromatography
– Gel permeation chromatography
– Mass spectroscopy
• Change in chemistry (IR, NMR)
MOLDING (Formation of drug polymer matrix)
Methods:1. Compression molding2. Melt molding3. Solvent casting
1.Compression molding
• Polymer and drug particles are milled to a particle size range of 90-150 µm
• Drug/polymer mix is compressed at approx. 30,000 psi• Formation of some types of tablet/matrix
MELT MOLDING
SOLVENT CASTING
APPLICATIONS OF BIODEGRADABLE POLYMERS
• Polymer system for gene therapy.
• Biodegradable polymer for ocular, tissue engineering, vascular,orthopedic, skin adhesive & surgical glues.
• Biodegradable drug delivery system for therapeutic agents such asanti-tumor, antipsychotic agent, anti-inflammatory agent.
• Polymeric materials are used in and on soil to improve aeration,and promote plant growth and health.
• Many biomaterials, especially heart valve replacements and bloodvessels, are made of polymers like Dacron, Teflon and polyurethane.
•
•
APPLICATION
APPLICATION
APPLICATION: as a Drug Delivery System
APPLICATION: as an ocusert
BIODEGRADABLE POLYMERS: Application in drug delivery
BIODEGRADABLE POLYMERS: Application in drug delivery
BIODEGRADABLE POLYMERS: Application in drug delivery
INDIVIDUAL APPLICATION OF BIODEGRADABLE POLYMERSPOLYMERS APPLICATION
Collagen In wound repairing
Chitosan Gelling agent
Dextran Plasma volume expander
Lectins As a mucoadhesive
Cyclodextrins, guar gum, pectin, insulin
Delivery of drug to colon
Poly -€-caprolactone Microspheres, implants
Rosin As an adhesive in TDDS
INDIVIDUAL APPLICATION OF BIODEGRADABLE POLYMERS
POLYMERS APPLICATION
PLA, PLGA
• Excipients for injectable drugs • PLA + Doxycycline…….periodontal disease• PLGA + Growth hormone…Growth
deficiency• PLA + Leuprolide acetate….Prostate
cancer
CONCLUSION
• Numerous synthetic biodegradable polymers are available and stillbeing developed for sustained and targeted drug delivery applications.
• Biodegradable polymers have proven their potential for thedevelopment of new, advanced and efficient DDS and capable ofdelivering a wide range of bioactive materials.
• However, only few have entered the market since many drugs faces theproblem of sensitivity to heat, shear forces and interaction betweenpolymers.
• These problems can be overcome by fully understanding thedegradation mechanism to adjust the release profile.
REFERENCES
• Kumari A, Yadav SK, Yadav SC (2010); “Biodegradable polymeric nanoparticles based drug delivery systems”; Colloids Surf B Biointerfaces
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