PEGylated versus non-PEGylated magnetic nanoparticles as camptothecin delivery system

Abstract

SummaryCamptothecin (CPT; (S)-(+)-4-ethyl-4-hydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14-(4H,12H)-dione) is a highly cytotoxic natural alkaloid that has not yet found use as chemotherapeutic agent due to its poor water-solubility and chemical instability and, as a consequence, no effective administration means have been designed. In this work, camptothecin has been successfully loaded into iron oxide superparamagnetic nanoparticles with an average size of 14 nm. It was found that surface modification of the nanoparticles by polyethylene glycol enables loading a large amount of camptothecin. While the unloaded nanoparticles do not induce apoptosis in the H460 lung cancer cell line, the camptothecin-loaded nanoparticle formulations exhibit remarkable pro-apoptotic activity. These results indicate that camptothecin retains its biological activity after loading onto the magnetic nanoparticles. The proposed materials represent novel materials based on naturally occurring bioactive molecules loaded onto nanoparticles to be used as chemotherapeutic formulations. The procedure seems apt to be extended to other active molecules extracted from natural products. In addition, these materials offer the potential of being further implemented for combined imaging and therapeutics, as magnetic nanoparticles are known to be multifunctional tools for biomedicine.

PEGylated magnetic nanoparticles (PEG@Fe 3 O 4 ) as cost effective alternative for oxidative cyanation of tertiary amines via C H activation

“…The obtained Fe 3 O 4 nanoparticles were subsequently functionalized with succinic acid as a linker to provide active COOH groups for ester bond formation with PEG [43]. Thus obtained succinic acid modified magnetic nanoparticles were treated with polyethylene glycol (PEG 300 ) in the presence of EDC (N-(3-dimethylaminopropyl)-N -ethylcarbodiimide hydrochloride) and ion exchanger (Indion 130) as shown in Scheme 2.…”

Exploring Factors for the Design of Nanoparticles as Drug Delivery Vectors

“…This is the case with CPT, whose high chemotherapeutic activity cannot be achieved with conventional aqueous soluble synthetic derivatives, such as topotecan or irinotecan, As cited previously, CPT has been successfully linked to organic NPs, such as those made of PLGA, and inorganic ones, such as gold or magnetic NPs . Other hydrophobic or poorly water soluble cancer drugs linked to NPs have also been cited, such as docetaxel in organic NPs, Sorafenib in silica NPs, Cisplatin in platinum NPs,, Paclitaxel in titania or honokiol in thermosensitive hydrogels…”

“…This way, CPT becomes adsorbed over the surface of bare NPs or entrapped between polymeric chains in the functionalized ones. It was shown through practice that while both formulations maintained apoptotic activity of CPT, pegylated NPs doubled the drug loading capacity of the bared ones …”

“…Another important consideration for the selection of the appropriate drug delivery mechanism is that it should not affect drug stability; as an example, the breaking of the lactone ring of CPT can be cited. This can happen due to the use of aggressive reagents, or because the method directly involves the functional groups on which drug activity relies …”

PhytoNanotechnology: Enhancing Delivery of Plant Based Anti-cancer Drugs

“…No significant difference in the cytotoxic activity was observed among the CPT loaded on either the PEGylated or bare magnetic NPs (% apoptotic cells 80% for both). However, a different behavior of PEGylated and non-PEGylated magnetic NPs can be expected due to longer circulation times of the PEGylated ones (Castillo et al, 2014). …”