Polymers for Drug Delivery - Sigma-Aldrich · PDF file2. Polymers for Drug Delivery....

POLYMERS FOR DRUG DELIVERY
Biodegradable Micro and Nanoparticles
Biodegradable Block Copolymer Micelles
Biodegradable Targeting Micro and Nanoparticles with Functional Polymers
Responsive Polymers
PEG Conjugation (PEGylation)
Polyoxazoline Conjugation
Dendrimers
Polymeric Hydrogels for Localized Delivery

2 Polymers for Drug Delivery
Sigma-Aldrich offers a diverse drug delivery toolbox that includes ready-to-use polymer and nanoparticle chemistries for directed and controlled delivery of small and large molecule therapeutics.
A major challenge in drug development is ensuring that each new candidate is delivered to the right place, at the right time and in the right amount. Low drug solubility, drug degradation, drug toxicity, or rapid clearance from the body can reduce the effectiveness of an otherwise promising candidate. Synthetic and natural polymers are both effective solutions for the delivery of small molecules, proteins, genes, or peptides.
Polymer Categories and Their Applications in Drug DeliveryControlled
ReleaseTargeted Delivery
Solubility Enhancement
Biodegradable micro and nanoparticles Biodegradable block copolymer micelles Biodegradable targeting micro and nanoparticles with functional polymers Responsive polymers PEG conjugation Polyoxazoline conjugation Dendrimers Polymeric hydrogels for localized delivery
Different polymer types can be used to control drug release rates, deliver a drug to the desired site of action, or increase drug solubility and reduce toxicity (increase biocompatibility).
TARGET ID &VALIDATION
LEADDISCOVERY
LEADOPTIMIZATION
PRE-CLINICALDEVELOPMENT
CLINICAL DEVELOPMENT
MANUFACTURING
TRANSLATIONAL RESEARCH SOLUTIONSPolymer Drug Delivery Techniques is just one part of Sigma-Aldrichs complete offer for academic Drug Discovery, a unique series of solutions that span Target ID & Validation through Pre-Clinical Development. Translational Medicine Solutions from Sigma-Aldrich are used by experts and non-experts alike to facilitate the cross-disciplinary research required for todays drug discovery.
To learn more about solutions that cover the entire drug discovery workflow, visit
aldrich.com/translational
Your Partner In Academic Drug Discovery
POLYMERS FOR DRUG DELIVERY

3For more information, visit sigma-aldrich.com
Targeted Delivery
Controlled Release
Biodegradable Micro and Nanoparticles
Polylactides Name Structure Degradation Time Mn PDI Prod. No.
Poly(L-lactide), PLLA OOH
O
CH3 n
CH3 >3 years
5,000 1.2 76459010,000 1.1 765112
20,000 1.1 764698
Poly(D,L-lactide), PDLLA CH3OOH
O
CH3 n

Natural PolymersName Structure Description Viscosity Prod. No.
Chitosan OOH
NH2
O
HO
HO
OOH
NH2
HO
n
low molecular weight20300 cP, 1 wt. % in 1% acetic acid (25 C, Brookfield) (lit.)
448869
medium molecular weight200800 cP, 1 wt. % in 1% acetic acid (25 C, Brookfield) (lit.)
448877
high molecular weight8002,000cP, 1wt. % in 1% acetic acid (25C, Brookfield) (lit.)
419419
Alginic acid sodium salt powder 1520cP, 1% in H2O (lit.) 180947
TRANSLATE DISCOVERIES INTOTHERAPEUTICS
Improve accuracy, reproducibility and confidence in your drug discovery and drug delivery research
Move your research forward with our polymer therapeutics solutions
sigma-aldrich.com/translational
Biodegradable Polymers: polylactide and polyglycolide (PLA, PGA, PLGA), RESOMER, and chitosan
Hydrophilic Polymers: PEGs, poly(2-oxazoline), PNIPAM Conjugated Nanomaterials: Au, Ag, iron oxide
nanoparticles, graphene oxide, and carbon nanotubes
Broad Selection of Polymerization Tools: monomers, initiators, and CRP agents
TARGET ID &VALIDATION
LEADDISCOVERY
LEADOPTIMIZATION
PRE-CLINICALDEVELOPMENT
CLINICAL DEVELOPMENT
MANUFACTURING
TRANSLATIONAL RESEARCH SOLUTIONS

Targeted Delivery
Controlled Release
Biodegradable Block Copolymer Micelles
Amphiphilic diblock copolymers consisting of a hydrophilic block (PEG) and a hydrophobic block (PLA, PGA, PLGA, PCL), have the capacity to form micelles to encapsulate hydrophobic drugs in order to increase drug solubility and facilitate delivery. The phase segregation of polymer blocks into a micellar morphology creates an environment where hydrophobic molecules can dissolve in the hydrophobic core.
Biodegradable Block CopolymersName PEG Mn B Block Mn PDI Degradation Time Prod. No.AB Diblock CopolymersPEG-PDLLA 2,000 2,200

Targeted Delivery
Controlled Release
Biodegradable Targeting Micro and Nanoparticles with Functional Polymers
Targeted delivery of drugs can be achieved through the conjugation of targeting moieties using functionalized polymers. For example, nanoparticles or micelles (i.e., PLGA nanoparticles), made with end-group functionalized polymers, can be grafted to specific targeting peptides, ligands, or antibodies through bioconjugation techniques.
Sigma-Aldrich offers: Biodegradable polymers with diverse end-groups amenable to a
variety of conjugation strategies.
End-functionalized Poly(L-lactide)sName Structure Mn PDI Prod. No.
Acrylate HCH3
OO
O
OCH2
O
n
2,500 1.2 775991
5,500 1.2 775983
Acetylene H O O CH
CH3
O
n
2,000 1.1 774162
5,000 1.1 774154
Amine H O O NH2
O
CH3 n
2,500 1.3 776378
4,000 1.2 776386
Azide H O O N3
O
CH3 n
5,000 1.2 774146
Maleimide OCH3
OO
N
O
On
H
2,000 1.2 746797
5,000 1.2 746517
Methacrylate H O O O CH2CH3
O
O
CH3n
2,000 1.1 771473
5,500 1.2 766577
Thiol H O O SH
CH3
O n
2,000 1.1 747394
2,500 1.2 747386
PLGA Particles
Conjugation with Targeting Moiety
Targeted Delivery
Controlled Release
Targeted Delivery
Controlled Release

Targeted Delivery
Controlled Release
Responsive Polymers
Stimuli-responsive polymers have been widely employed to enable targeted delivery and controlled release in response to changes in their environment. Stimuli-responsive polymers undergo rapid changes in their microstructure from a hydrophilic to hydrophobic state, triggered by external stimuli, including heat, pH, and ionic strength. Drug delivery systems (micelles, microgels, and hydrogels) composed of responsive polymers release the drug during the collapse and expansion of the network in the aqueous environment. The most extensively investigated temperature/pH sensitive systems are based on poly(N-isopropylacrylamide) (PNIPAM).
Polymeric Micelle-drug Complex
Below LCST
Drug Release Acceleration and Cellular Adsorption Enhancement
Above LCST
Poly(N-isopropylacrylamide) (PNIPAM)Structure Molecular Weight Prod. No.
O NH
n
H3C CH3
Mw20,00040,000 535311
End-functionalized PNIPAMStructure Functional End Group Average Mn Prod. No.
SSi
NHOn
CH3H3C
O
O
O
CH3CH3
CH3
Amine2,500 7248235,500 724831
Azide 15,000 747068
Carboxylic acid
2,000 7248155,000 7248077,000 724866
10,000 724459
N-hydroxylsuccinimide (NHS) ester2,000 725668
15,000 747068
Maleimide2,000 7310485,500 728632
Triethoxysilane 2,500 760978
Temperature and pH Sensitive PNIPAM CopolymersCopolymer Average Mn LCST Prod. No.Poly(NIPAM-co-BA) BA 12 mol % 30,000 1416 C 762881Poly(NIPAM-co-BA) BA 5 mol % 30,000 25 C 762857Poly(NIPAM-co-MAA-co-ODA)* MAA 5 mol %, ODA 1 mol % 30,00060,000 2232 C 724475Poly(NIPAM-co-MAA)* MAA 5 mol % 30,00050,000 2932 C 724467Poly(NIPAM-co-MAA)* MAA 10 mol % 60,000 2932 C 724858Poly(NIPAM-co-MAA)* MAA 10 mol % 8,00010,000 3337 C 750166Poly(NIPAM-co-AA)* AA 15 mol % ** 3236 C 741930Poly(NIPAM-co-AAm) AAm 15 mol % 20,00025,000 3034 C 738735Poly(NIPAM-co-AAm) AAm 10 mol % 20,000 3438 C 738727
BA: butylacrylate, MAA: methacrylic acid, ODA: octadecyl acrylate, AA: acrylic acid, AAm: acrylamide *pH sensitive **Linear hydrogel, viscosity 7,50012,500 cPs (5 wt. % in H2O, 25 C)
Sigma-Aldrich offers: Temperature- or pH-responsive hydrophilic polymers, such as
end-functionalized PNIPAMs, allow for the activation of a payload upon delivery.
Targeted Delivery
Controlled Release

Targeted Delivery
Controlled Release
PEG Conjugation (PEGylation)
Poor drug solubility and biocompatibility is a significant challenge with many new drug candidates. Modifying a drug by attaching a functional PEG can enhance drug solubility, reduce protein aggregation, and decrease immunogenicity. By increasing the molecular mass of proteins and peptides and shielding them from proteolytic enzymes, PEGylation improves pharmacokinetics. The proper molecular weight selection of the PEG linker can significantly enhance the solubility and distribution of a drug candidate within an organism.
PEGylation
Increased hydrodynamic size Longer half-life Impr

Polymers for Drug Delivery - Sigma-Aldrich · PDF file2. Polymers for Drug Delivery....

Documents

Transcript of Polymers for Drug Delivery - Sigma-Aldrich · PDF file2. Polymers for Drug Delivery....