Enhanced uptake of polyethylene glycol coated gold nanoparticles for improved therapeutics

Polyethylene glycol (PEG) has promoted the prospective cancer treatment applications of gold nanoparticles (GNPs). PEG is widely used in providing GNPs with stealth properties, hence prolonging blood circulation times. GNPs coated with PEG (PEG-GNPs) take advantage of the enhanced permeability and retention effect in tumor environments, making them suitable for targeted treatment. The cellular uptake of PEG-GNPs is significantly lower than uncoated GNPs in vitro. PEG minimizes PEG-GNP interaction with ligands that mediate cancer cell uptake, causing reduced GNP uptake in comparison to uncoated GNP. As intracellular localization of GNPs maximizes its therapeutic enhancement, there is a need to improve the uptake of PEG-GNPs. To improve cell entry, receptor mediated endocytosis peptides were conjugated with PEG-GNPs of varying core sizes. Spherical GNPs of diameters 14, 50 and 70 nm with a PEG chain length of 2 kDa were used to determine a preferred core size for uptake in vitro in HeLa and MDA-MB-231 cells. A preliminary study using surface-modified GNPs as a radiosensitizer to a megavoltage clinical photon beam was done to assess its therapeutic application.

Enhanced uptake of polyethylene glycol coated gold nanoparticles for improved therapeutics

Polyethylene glycol (PEG) has promoted the prospective cancer treatment applications of gold nanoparticles (GNPs). PEG is widely used in providing GNPs with stealth properties, hence prolonging blood circulation times. GNPs coated with PEG (PEG-GNPs) take advantage of the enhanced permeability and retention effect in tumor environments, making them suitable for targeted treatment. The cellular uptake of PEG-GNPs is significantly lower than uncoated GNPs in vitro. PEG minimizes PEG-GNP interaction with ligands that mediate cancer cell uptake, causing reduced GNP uptake in comparison to uncoated GNP. As intracellular localization of GNPs maximizes its therapeutic enhancement, there is a need to improve the uptake of PEG-GNPs. To improve cell entry, receptor mediated endocytosis peptides were conjugated with PEG-GNPs of varying core sizes. Spherical GNPs of diameters 14, 50 and 70 nm with a PEG chain length of 2 kDa were used to determine a preferred core size for uptake in vitro in HeLa and MDA-MB-231 cells. A preliminary study using surface-modified GNPs as a radiosensitizer to a megavoltage clinical photon beam was done to assess its therapeutic application.

Impact of Chain Length on Release Behavior of Modified Polyethylene Glycol Intercalated-Montmorillonite Nanocomposite

A new drug delivery nanocomposite system was prepared from sodium montmorillonite (Na+Mt) intercalated with modified polyethylene glycol (PEG). PEGs of different molecular weights (400, 4000, and 8000) were modified with glycidyltrimethylammonium chloride (GTMAC) to provide terminal quaternary ammonium sites capable for attaching with Mt or other materials through ion exchange. The modified PEG-GTMAC derivatives were reacted in excess amount with Na+Mt through ion exchange. The remaining quaternary sites were used for the attachment of sodium diclofenac as a model drug. The structures of the prepared clay-modified PEG-diclofenac systems were characterized using Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). The release behavior of diclofenac from the different nanocomposites was studied at different pH values. With regard to the PEG chain length, the drug release increased with increasing PEG molecular weight (GCDIII > GCD-III > GCDII > GCDI). The kinetics of the release models was discussed using Korsmeyer–Peppas, Higuchi, and zero- and first-order models. The results of the kinetics study revealed that modified samples with PEG 400 and PEG 4000 (GCD-I and GCDII) exhibited non-Fickian diffusion (anomalous transport) while modified samples with PEG 8000 (GCDIII) exhibited super case-II transport.

Toward Understanding Curcumin Delivery by Trimethyl Chitosan -polyethylene Glycol: Optimization Ofpolymer Concentration and Chain Length by Molecular Dynamics

The second main cause of death in the world and one of the major public health problems is cancer. Curcumin is anatural bioactive substance with good anti-cancerous effect.However, due to thelow cellular uptake of curcumin anti-cancer drug, it is vital to exploit a noble formulation, which can contribute to a decrease in its hydrophobicity and enables theefficient therapeutic effect of curcumin. Biocompatibility and hydrophilicity of the polyethylene glycol cause itto be one of the most attractive drug carriers. Chitosan is also of great importance, consideringits biocompatibility,and is used along with thedrug-carrying polymers. In this study, for the first time, a combination oftrimethyl chitosan and polyethylene glycol was employedto deliver curcumin.Herein, hydrophilicity, stability, and energy analysis of the systems have been investigated, from which it was found thatthe 60/40 is the optimum ratio concentration ofchitosan to polyethylene glycol for Curcumin delivery. Another characteristic property of the hybrid drug delivery system was the PEG chain length, with its least magnitude being the optimal value. Results of the present molecular study give a practicalinsight into the curcumin drug delivery system and propose a novel hybrid carrier for efficient curcumin delivery, which can be further exploited to develop novel nanomedicine systems.

Long-Acting HIV-1 Fusion Inhibitory Peptides and their Mechanisms of Action

The clinical application of HIV fusion inhibitor, enfuvirtide (T20), was limited mainly because of its short half-life. Here we designed and synthesized two PEGylated C34 peptides, PEG2kC34 and PEG5kC34, with the PEG chain length of 2 and 5 kDa, respectively, and evaluated their anti-HIV-1 activity and mechanisms of action. We found that these two PEGylated peptides could bind to the HIV-1 peptide N36 to form high affinity complexes with high α-helicity. The peptides PEG2kC34 and PEG5kC34 effectively inhibited HIV-1 Env-mediated cell–cell fusion with an effective concentration for 50% inhibition (EC50) of about 36 nM. They also inhibited infection of the laboratory-adapted HIV-1 strain NL4-3 with EC50 of about 4–5 nM, and against 47 HIV-1 clinical isolates circulating in China with mean EC50 of PEG2kC34 and PEG5kC34 of about 26 nM and 32 nM, respectively. The plasma half-life (t1/2) of PEG2kC34 and PEG5kC34 was 2.6 h and 5.1 h, respectively, and the t1/2 of PEGylated C34 was about 2.4-fold and 4.6-fold longer than C34 (~1.1 h), respectively. These findings suggest that PEGylated C34 with broad-spectrum anti-HIV-1 activity and prolonged half-life can be further developed as a peptide fusion inhibitor-based long-acting anti-HIV drug for clinical use to treat HIV-infected patients who have failed to respond to current anti-retrovirus drugs.