Novel drug carrier that maximizes therapeutic potential
- Alternative to PEGylation
- No modification of API
- Extend API half life and bioavailability
- Increase stability and improve safety of API
- Target API to diseased and inflamed tissue
- Bind peptides, proteins, and RNA
to topHydrophobic CoreTM
This platform consists of a hydrophobic reversible binding moiety. The specific molecule used varies, but often consists of a fatty acid chain with 18-22 carbons. The length of this molecule may be adjusted to optimize the binding affinity of the drug to the carrier. In essence, this creates a carrier with properties much like a reverse-phase HPLC column. Many proteins and peptides have hydrophobic domains which bind with high affinity to the PGC-HCTM carrier.
Applications: Glucagon like peptide-1 (GLP-1), a human hormone involved in glucose control, insulin secretion, and gastric emptying
to topMetal BridgeTM
This platform takes advantage of the metal binding properties of some proteins and peptides to create a high affinity interaction between the drug and carrier. In this platform, the reversible binding moiety is a metal chelator, typically binding Zn or Cu. With the addition of a metal ion, the resulting carrier coordinates metal binding molecules with high affinity. Insulin, for example, has a high affinity for Zn and binds the PGC-MBTM carrier with nanomolar affinity.
Applications: Native Human Insulin (has a high affinity for Zn ions)
to topAnionic CoreTM
This platform consists of an anionic reversible binding moiety such as chondroitin sulfate. In essence, this creates a carrier with properties much like an ion-exchange column. Many proteins and peptides have charged domains which bind with high affinity to the PGC-ACTM carrier.
Applications: Basic peptides or protein that contain amino acid residues such as lysine or arginine which are positively charged at physiological pH such as heparin-binding Epidermal Growth Factor.
to topOligo CoreTM
This platform consists of oligonucleotide reversible binding moiety such as polyG, polyC, polyA or polyT. The specific molecule used varies, but will contain an oligonucleotide complementary to the binding moiety. In essence, this creates a carrier with properties which take advantage of polynucleotide complementation. The affinity can be changed by changing the number of complementing oligonucleotides.
Applications: drugs that contain RNA or DNA.
to topPGCTM Affinity Binding Mechanism
The loading and release of the API / drug from PGCTM is equilibrium based, with a Kd that favors binding.
PGCTM loaded with drug
|Kd =||[Free Drug] [Empty PGCTM sites]||= ~10 -9 M|
|[Total PGCTM sites]|
to topPGCTM Application Guide
|PGCTM Technology||Load Molecule Attributes|
|Anionic CoreTM||Isoelectric point > 8.0
multiple formal charges
Note: Loading is defined as weight of API per weight of carrier, so 10% loading is 10 mg of API per 100 mg carrier.
to topPro-drug Technology with PGCTM
PGCTM protects the peptide-ligand conjugate. When the peptide-ligand conjugate is released from the PGCTM, the linker is cleaved to release active peptide into the blood.
to topAdvantages of PGCTM
Affinity based binding of drug to carrier
- No irreversible chemical modification of drugs
- Improves PK, solubility, and safety
- Useful for peptides, proteins, and potent small molecules
- Ease of formulation and manufacturing
- Passive targeting to areas of enhanced vascular permeability (inflammation, infection, and tumors)
- Active targeting capability
- Strong IP
- SC, IV, and IM
to topComparison of PGCTM to Other Systems
|PGCTM is Superior to No Carrier||PGCTM is Superior to HESylation & PEGylation||PGCTM is Superior to Liposomes & Micelles|
to topSolubility Case Study
Formulated with PGC-hydrophobic coreTM
to topPGCTM dramatically extends bioavailability and pharmacokinetics when formulated with peptides
ANP example in dog
Unformulated ANP peptide (red) is cleared in minutes while PGC-formulated-ANPTM (blue) lasts for days.
to topLigand-TerlipressinTM pro-drug example in rats
Unformulated Ligand-Terlipressin peptide (“free”, orange) is cleared in minutes while PGC-formulated-Ligand-TerlipressinTM (green) lasts for days.
to topMechanism of Passive Targeting from Enhanced Permeability and Retention
Healthy blood vessels (A)
Sites of infection, inflammation, and in tumors (B)
to topPGCTM Targets Inflammation and Infection
Enhanced permeability and retention and long circulation enables accumulation of PGCTM loaded with imaging agent to damaged tissue
to topPGCTM Tumor Targeting
Accumulation of PGC-formulated-APITM in tumors is a result of long circulation and enhanced permeability and retention effects
Rat breast tumor model imaged with PGCTM and co-labeled with Gd and 111In; Fisher rat at 48 hrs.
© PharmaIN 2016