Introduction

Polyethylene glycols are the polymers or hydrophilic oligomers produced from ethylene oxide, comprising of repeating units of – (O - CH2 - CH2) -. PEGs are manufactured in huge range of molecular weights, denoted as “monodispersed” with the defined PEG molecular weight and chain size, or “polydispersed” polymers with the help of Gaussian distribution of molecular weights and chain lengths. The capability to assign various reactive functional groups to the terminal sites of PEG polymers have expanded their advantages. Homo and hetero bifunctional PEG derivatives are appropriate as the cross-linking agents or spacers within the chemical ent

Introduction

Polyethylene glycols are the polymers or hydrophilic oligomers produced from ethylene oxide, comprising of repeating units of – (O - CH2 - CH2) -. PEGs are manufactured in huge range of molecular weights, denoted as “monodispersed” with the defined PEG molecular weight and chain size, or “polydispersed” polymers with the help of Gaussian distribution of molecular weights and chain lengths. The capability to assign various reactive functional groups to the terminal sites of PEG polymers have expanded their advantages. Homo and hetero bifunctional PEG derivatives are appropriate as the cross-linking agents or spacers within the chemical entities, where mono-functional PEGs are protecting the bridging reactions that affect the PEGylation of various compounds with the bifunctional PEGs.

The procedure of PEGylation, covalent grafting of PEG derivative on molecules, enhances the water biocompatibility and solubility, specifically used for the development of the drug. Products based on PEGylated needs a huge characterization with the analytical and critical techniques for enduring the regulatory compliance for the applications of medicine. Derivatives of bifunctional PEG are continuously used for the PEGylation of proteins, peptides, small molecules such as mannose, folate, oligonucleotides, prodrugs, nanoparticles, cells, surfaces and virus particles. Derivatives of multi-arm PEG work in the formation of hydrogels for the controlled release of therapeutics in medical devices, regenerative medicine and several applications involving wound healing and cell culture. Important developments were done in the year 2014 by the scientific community in research & development for innovative applications for PEGs.

Polyethylene Glycols Applications for the Targeted Diagnostics and Cancer Drug Delivery

Efforts of R&D on the innovative applications of the PEG derivatives are concentrating on the drug delivery & targeted diagnostics by direct PEGylation of therapeutics or the PEG containing vehicles like liposomes, micelles, nanoparticles and dendrimers. Significant parameters influencing the bioactivity of PEGylated drugs involve the PEGylation site, length of PEG chain, temperature particular for PEGylation reaction and linker chemistry. For instance, heat treatment was displayed to enhance the bioactivity of C-terminally PEGylated staphylokinases, where the amyl linker for around 20 kDa PEG developed the bioactivity of staphylokinases. Picking the organic solvent for the hydrophobic proteins have the capability of reducing the price of reaction times and reagents where parameters are significant for the PEGylation processes on the industrial scale. Amongst the enhancements done for therapeutics by PEGylation is the developed water solubility, controlled release, enhanced stability, prolonged drug and the improved pharmacodynamics/ pharmacokinetic profile.

In the development of PEGylation of small molecule drugs, multi-arm polyethylene glycol link the drug molecules, enduring huge drug load and improved drug release function. As an instance, the growing molecular weight of iRGD peptide by the prolonged PEGylation into macromolecular extravasation and the complete penetration of drug in tumors and enhanced pharmacokinetic profile of iRGD to the unmodified peptide.

PEG-containing vehicles for the drug delivery like dendrimers, liposomes, micelles or nanoparticles are the best substitutes to the PEGylation of drugs. Liposomes experience the inert extravasation to the tumor tissues where the ligands are unprotected with the controlled exogenous administration of decreasing l-cysteine. Consequently, RGD identify integrins, expressed on the malignant tumors, searching deep in the vascular tumor spheroids and the internalization in synergistic effect with TAT. For the drug delivery, the inserting area within the alkyl grafts of reducible polymers and the oleic acid layer on the nanoparticles surface stored the hydrophobic drug whereas PEG chains enhanced the dispersion of nanoparticles in the aqueous environment.

Polyethylene Glycol Applications in Tissue Regeneration and Wound Healing

Amongst the main uses of PEG hydrogels are the utilization as adhesives for the wound closure, wound healing, controlled release matrices for therapeutics, regenerative medicine tools and part of the medical devices. The behavior of swelling, storage moduli of hydrogel bioadhesive and degradation profiles were familiar by altering the degree of oxidation of alginate. The level of adhesion was improved on the porcine skin model on comparing the commercially available fibrin glue. The effect of pH on the intermolecular cross-linking and connection to biological substrates permitted the recognition of optimal buffering pH for the formulation of adhesive. On testing the adhesive for pericardium tissue, the formulation pH of around 7.5 offered the perfect model of the mechanical properties, curing rate and the interfacial binding ability for the Catechol comprising of the PEG hydrogel with dopamine.

The molecular weight of the polyethylene glycol chain does not have a substantial effect on cell division and the glycosaminoglycan production as the part of composite hydrogels. Similarly, for the regenerative medicine purposes, a ‘tissue engineered periosteum’ is generated by using the hydrolytically degradable PEG hydrogels to localize and transplant mesenchymal stem cells to allograft the surfaces. The method developed the healing graft vascularization, biomechanical strength and the endochondral bone formation on comparing the untreated allografts. The procedure of endochondral ossification on comparing the untreated allografts, needing future supplementation of hydrogels with additives to accelerate the procedure of ossification for treating the crucial sized bone defects.

Polyethylene Glycol Applications in Tissue Models and Cell Culture

PEG-copolymer and PEG hydrogels are the solutions as scaffolds used for cell culture, for the controlled release of therapeutics and the other applications not limited to tissue engineering. PEG hydrogels with the physiologically related matrix diffusion distance and elasticity, invented in transwell inserts used by the cell culture of valvular endothelial and interstitial cells. Increase in the cells of PEG hydrogel matrices have permitted the appropriate investigations associated to the valve stenosis progression and initiation.

Bio-synthetic tissue scaffold comprising the interpenetrating network of gelatin methacrylamide polymerized in the polyethylene glycol framework for the endothelial cells culture. The tissue model presented the huge cytoplasmic spreading and the cellular adhesion, with the continued viability and the proliferation for adherent and encapsulated cells.

The hydrogel the system was based on the macromere of polyethylene glycol permitted the superficial incorporation of bioactive peptides for the enhanced cell-matrix interactions. The 3D hydrogel system is regulating the expression of NCTP in summarized HepG2 and Huh7 cell lines and the hepatocyte-like polarity, deprived of genetic modification and requirement for chemical additives and growth factors.

Conclusion

Various uses of polyethylene glycol and PEG hydrogels are used in drug delivery, cancer diagnostics, wound healing, tissue scaffold models, cell culture and tissue regeneration. Other applications of polyethylene glycol involve PEGylation of large and small molecules like proteins, peptides, mannose, folate, PEGylation of cells, oligonucleotides, virus & nanoparticles and modification of the surface.