1. polyethyleneimine (PEI) In light of abundant evidence obtained so far, we have a much better understanding of polyethyleneimine (PEI), a cationic synthetic polymer, and its properties in drug delivery and, more than ever, we understand the high potentials of this gold standard polymer, especially in gene delivery. PEI-based systems have been employed to deliver active agents including drugs, nucleic acids, and bioactive molecules, and the feasibility and the possibility of clinical applications of these delivery systems have been explored so far. 2. Polyethylene glycol (PEG) Polyethylene glycol has a long history of use in drug delivery fields. This synthetic polymer is widely employed to cover the surface of the main delivery system, the process called PEGylation, to modify the properties of the designed carrier. The so-called PEGylation process can significantly reduce the toxicity of the delivery system, especially in the case of highly cationic polymers since, as mentioned previously, cationic charges interact with blood components. It also prolongs blood circulation time providing more chance of the drug/gene accumulation at the tumor site. 3. Chitosan Chitosan, a linear natural polysaccharide, possesses interesting features. The current literature on this polymer abounds with a lot of examples in many fields such as agriculture, water filtration, weight loss products, winemaking, food preservation, bio-printing, and biomedical uses. The employment of chitosan in drug delivery fields has been reported in many researches; thus, we have a way deeper understanding of this polymer than ever. Chitosan is a highly biocompatible and biodegradable polymer with very low toxicity both in vitro and in vivo. 4, Poly (D, L-lactic acid) (PLA), poly (glycolic acid) (PGA), poly (lactic-co- glycolic acid) Poly (D, L-lactic acid) (PLA), poly (glycolic acid) (PGA), and poly (lactic-co-glycolic acid) (PLGA) seem to have some similar properties that a number of studies have decided to argue about them and treat them as they are in a united group. Indeed, the key properties that have been seen in these three synthetic polymers are their high biocompatibility, biodegradability, and non-toxic features on which a lot of research have been made and which also brightened the hope of more clinical trials with these polymers. Thanks to their old history of application, a massive data is now available in the use of these polymers in drug delivery systems. PLGA has versatile degradation kinetics, and due to the high flexibility of PLGA, the physical properties of the obtained nanoparticles can be easily controlled by adjusting the suitable L:G ratio (lactate to glycolic acid ratio). PLGA NPs have been 4 Application of Polymers|successfully proven to be efficient carriers of large biomolecules such as vaccines and proteins. An active pharmaceutical ingredient (API) appears to be dispersed homogeneously within the PLA matrix. In a comparison between PLGA and PGA, PGA polymers possess amide groups which make modification with biologically active moieties possible and easier. . Hyaluronic acid (HA) Hyaluronic acid (HA) is a linear high molecular weight natural biopolymer that consists of repeating d-glucuronic acid and N-acetyl-d-glucosamine disaccharide units. This natural polymer exists in the human body mainly found in the extracellular matrix of connective tissues, indicating the possible non-toxic features that can be expected from hyaluronic acid-based NPs. HA is highly biocompatible and biodegradable and is gradually degraded by enzymes such as hyaluronidases in the body. This unique polymer has been widely applied in medicine for tissue engineering, drug delivery, and molecular imaging, indicating a massive data is available on it and the toxicity profile of the polymer has been well studied. It is well established by many studies that tumor cells overexpress CD44 receptors on them which is a potent receptor for HA. Polycaprolactone (PCL) Polycaprolactone (PCL) is a synthetic biodegradable polyester approved by the Food and Drug Administration (FDA) as a drug delivery system. The application of PCL as a device in biomedical implants has almost an old history of use, but the use of this polymer as a compartment of a drug delivery system has attracted a great deal of attention, recently. Indeed, the acceptable toxicity profile of PCL encourages the attempts for clinical applications. The presence of ester linkage groups in PCL structure opens the ways of hydrolysis in the human body resulting in such biodegradability which is favorable in a given drug/gene carrier. PCL-based NPs appear to have a prolonged circulation property, bringing more chances for the medicine to reach the action site. They also seem to have a high drug- loading capacity which widens the choices of selected drugs/genes (Wang et al. PEG-PCL NPs were reported to have high biocompatibility and biodegradability and long circulation time in the delivery of a wide range of therapeutic agents. . Polyorthoester (POE) POE with the general structure -[-R-O-C(R1, OR2)}-O-R3-]n— is a synthetic biodegradable and highly hydrophobic polymer that follows a zero-order drug release kinetics in the physiological environment. The release profile of POE can be adjusted by choosing the appropriate molar ratio of latent acid in the polymer chains as well as lipophilicity of the diol and polymer molecular weight, indicating the degradation time of POE-based polymers can be easily controlled. 5 Application of Polymers|8. Poly (methyl methacrylate) (PMMA) PMMA is the synthetic polymer of methyl methacrylate approved by the Food and Drug Administration (FDA) for medical applications. The highlighting feature of PMMA is its biocompatibility. To take advantage of this feature in one study, PEI-PMMA were synthetized for gene delivery and the obtained NPs efficiently delivered DNA into HeLa cells. In another report, cellulose-graft-poly (methyl methacrylate) nanoparticles loaded with betulinic acid (BA) demonstrated perfect biocompatibility in vitro and in vivo and better anti-tumor efficiency with reduced side effects. 9. Polyvinylpyrrolidone (PVP) PVP with synthetic origin has been also used in some studies to investigate its drug delivery features. In a study, Praseetha et al. coated magnetic nanoparticles with PVP polymer and then coated the whole carrier with folic acid (FA) for specific targeting of an anticancer drug (epirubicin hydrochloride) to cancer cells. They revealed that PVP-coated NPs had a better anti-tumor response than PVP uncoated NPs. 6 Application of Polymers|