Polymer Characterisation

Question 1

Different Drug Deliver Polymers Classes

Answer 1

Polymerics drugs, polymer-drug conjugates, micro/nano-particulate drug carriers, macroscopic drug carriers, coatings and matrix excipients

Question 2

Polymeric Drugs Outline

Answer 2

Polymers as API (not carrier or pro-drugs). Eg; Glatiramer Acetate

Question 2

Glatiramer Acetate Outline

Answer 2

Immunomodulator to treat MS, reduces relapse risk (not progression). Randomly sized polypeptides composed of 4 amino acids (mixed randomly)

Question 3

Glatiramer Acetate Formation

Answer 3

Chain formation. Initiator compound opens ring on amino acid rings (N-Carboxyanhydride)

Question 4

3 Methods of Polymeric Drug Release

Answer 4

Diffusion-Controlled (matrix, reservoir), Solvent-Controlled (osmotically or swelling controlled) and Chemically-Controlled (covalent-polymer backbone, rate controlling membrane and bio erodible polymer)

Question 5

Why are polymers used in drug delivery

Answer 5

Increases the potency of drugs by making delivery mor efficient (less drug lost by metabolism, reduces toxicity, sustained release). But tends to reduce a compounds hydrophilicity

Question 6

Polymeric Drug Delivery Considerations

Answer 6

complex nature, site of action (pH, ligands), excretion route (eg kidneys), biodegrading,

Question 7

Drug to polymer covalent bond release

Answer 7

Drug released when enzyme at target site cleaves covalent bond, releasing drug to bind with receptor. May contain targeting moiety to increase specificity to target site (reduce off target action. Eg; Paclitaxel (Taxol)

Question 8

Hoe Does Enhanced Permeability and Retention Effect Drug Delivery

Answer 8

Helps deliver drug to tumour site (selectivity) as drug can only move through vessel at that site, so only attacks tumour

Question 9

Hydrophilic Polymers Delivering Hydrophobic Drugs

Answer 9

Nano spheres/capsules, lipo/polymersomes, micellar systems and conjugates

Question 10

Nanospheres & Nanocapsules Outline

Answer 10

Solid polymeric matrix/shell and liquid inner core (drug)

Question 11

Liposomes and Polymersomes Outline

Answer 11

Phospholipid bilayers with PEG brushes or amphiphilic block copolymers

Question 12

Micellar Systems Outline

Answer 12

Linear Polymers (formed by amphilic copolymers), star-shaped (hydrophobic core encloses drug) and dendritic (dense outer share)

Question 13

Pegylation Outline

Answer 13

PEG may result in increased retention, may result in adverse events

Question 14

Components of Pegylated Small Molecules

Answer 14

PEG (biggest component, by a lot), linker (hydrolytic, enzyme sensitive, smallest) and drug

Question 15

Paclitaxel (Taxol) Outline

Answer 15

Chemotherapy for multiple cancers. Poor aqueous solubility naturally. Conjugated to poly(L-glutamic acid) aka PG by ester linkage

Question 16

Hydrophobic Matrix System

Answer 16

Release by polymer erosion/diffusion. Polymers form a barrier to drug movement and protects drug from environment. Includes: Nanoparticles, Microcapsules, Microspheres and Film Coatings

Question 17

3 Mechanisms of Biodegradation

Answer 17

Cleavage of water soluble polymer crosslinks, cleavage/transformation of side chain to polar (charged) & backbone linkage cleavage

Question 18

Poly(glycolic acid) Outline

Answer 18

Highly crystalline (brittle), high melting point (225-230 C) and polar (not soluble in non-polar)

Question 19

Poly(lactide acide) Outline

Answer 19

Chiral (L and D confirmations), both semicrystalline and D conformation is amorphous (Tg 55-60 C)

Question 20

PLGA Outline

Answer 20

Copolymer of PGA and PLA. Ratio effects crystallinity (degradation). Higher PGA = faster degradation

Question 21

PLGA In Vivo Release Profile

Answer 21

Increasing lactic acid slows the release of drug

Question 22

Microencapsulation Outline

Answer 22

encapsulation of small particles of drug is a polymer film or coat

Question 23

Microspheres Outline

Answer 23

Solid particles that capture a drug

Question 24

Polymer Vectors in Gene Therapy

Answer 24

Polymer (cationic (positive)) and nuclaic acid (anionic (negative)). Eg; polyethylene amine (PIE), polyamidoamine (PAMAM) dendritics, polylysine (PLL)

Question 25

Relationship between dendritic fold and gene delivery

Answer 25

More folds = lower gene degradation risk