PGA – Poly(Glutamic Acid)
A Modern versatile Polymer as Drug Carrier for Drug Delivery,
Tissue Engineering, Sensing, Catalysis, NanoMedicinen
Poly(glutamic acid) is a biocompatible and biodegradable polymer, which can be conjugated through side chain condensation with any suitable molecule. Due to a controlled proprietary and patented process with living polymerization technology a superior quality of PGA is being achieved. Usual poly amino acids carry significant amount of cyclic structures, carbamates or isocyanates. Through a very well controlled polymerization process well defined terminal groups and polymeric structure is being achieved in high purity and with superior polydispersity. Through "living polymer" technology also multifunctional PGA polymers can be produced through post polymerization modification.
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PGA can be used for polymer therapeutics application for large biopharmaceuticals and also for small molecule drugs. A controlled loading of small molecules onto PGA polymer can be achieved and brings the advantage of polymer therapy also to small molecules.
In the following published application PGA equips a hydrophobic small peptoidic drug molecule, which has poor water solubility, with superior pharmacokinetic properties excellent water solubility and increases membrane permeability.
Modulation of Cellular Apoptosis with Apoptotic Protease-Activation Factor 1 (Apaf-1) Inhibitors L. Mondragón, M. Orzáez, G. Sanclimens, A. Moure, A. Armiñán, P. Sepúlveda, A. Messeguer, M. J. Vicent, E. Pérez-Payá; J. Med. Chem. 2008; 51: 521-529.
Drug Carrier and Release System for Multiple Drug Therapy
Through post polymerization modification PGA can be equipped with additional functional groups, like alkyne or azides for click conjugation, however, also the basic polymer can be loaded with different molecules as shown in the following example.
Paclitaxel (PTX) is a widely-used potent cytotoxic drug that also exhibits anti-angiogenic effects at low doses. However, its use at its full potential is limited by severe side effects. The PGA polymer PTX nano-scaled conjugate passively targets tumor tissue exploiting enhanced permeability and retention effect. The polymer is enzymatically-degradable leading to PTX release under lyosomal acidic pH. The cyclic RGD peptide enhances the effect of PGA-PTX alone by targeting ανβ3 integrin, which is overexpressed on tumor endothelial and epithel cells.
Integrin-assited drug delivery of nano-scaled polymer therapeutics bearing paclitaxel Anat Eldar-Boock, Keren Miller, Joaquin Sanchis, Ruth Lupu, Maria J. Vicent, Ronit Satchi-Fainaro Biomaterials 2011; 32: 3862-3874.
Bi-functional Drug Carrier available for
Sophisticated Applications Combination Therapy – Personal Medicine
Azido: Conjugation via Click Chemistry
Propargyl: Conjugation via Click Chemistry