In past two decades poly lactic-co-glycolic acid (PLGA) has been among the most attractive polymeric candidates used to fabricate devices for drug delivery and tissue engineering applications. PLGA is biocompatible and biodegradable, exhibits a wide range of erosion times, has tunable mechanical properties and most importantly, is a FDA approved polymer. In particular, PLGA has been extensively studied for the development of devices for controlled delivery of small molecule drugs, proteins and other macromolecules in commercial use and in research. This manuscript describes the various fabrication techniques for these devices and the factors affecting their degradation and drug release.

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Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier

Nanoparticles in cancer therapy and diagnosis

Nanoparticle (NP) drug delivery systems (5−250 nm) have the potential to improve current disease therapies because of their ability to overcome multiple biological barriers and releasing a therapeutic load in the optimal dosage range. Rapid clearance of circulating nanoparticles during systemic delivery is a critical issue for these systems and has made it necessary to understand the factors affecting particle biodistribution and blood circulation half-life. In this review, we discuss the factors which can influence nanoparticle blood residence time and organ specific accumulation. These factors include interactions with biological barriers and tunable nanoparticle parameters, such as composition, size, core properties, surface modifications (pegylation and surface charge), and finally, targeting ligand functionalization. All these factors have been shown to substantially affect the biodistribution and blood circulation half-life of circulating nanoparticles by reducing the level of nonspecific uptake, de...

http://pubs.acs.org/doi/pdf/10.1021/mp800051m

Factors Affecting the Clearance and Biodistribution of Polymeric Nanoparticles

PEGylation as a strategy for improving nanoparticle-based drug and gene delivery

PEGylated PLGA nanoparticles as protein carriers: synthesis, preparation and biodistribution in rats

PEGylated polycyanoacrylate nanoparticles as tumor necrosis factor-α carriers

The objective of this study was to investigate the pharmacokinetics and in vivo anti-tumor effect of recombinant human tumor necrosis factor-α (rHuTNF-α) encapsulated in poly(methoxypolyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate) (PEG-PHDCA) nanoparticles. Our experimental results showed that PEG-PHDCA nanoparticles could extend the half-life of rHuTNF-α to 7.42 h and obviously change the protein biodistribution in tissues, and in particular, increase accumulation of rHuTNF-α in tumor. Compared with PHDCA nanoparticles and free rHuTNF-α, PEG-PHDCA nanoparticles loaded with rHuTNF-α showed higher anti-tumor potency at the same dose, which might be related to its higher accumulation in tumor tissues and longer plasma circulation time. Therefore, PEG-PHDCA nanoparticles could be an effective carrier for rHuTNF-α.

https://www.jstage.jst.go.jp/article/bpb/24/6/24_6_662/_pdf

Stealth Polycyanoacrylate Nanoparticles as Tumor Necrosis Factor-α Carriers: Pharmacokinetics and Anti-tumor Effects

The aim of the present work was to investigate and assess the merit of PEGylated recombinant human tumor necrosis factor-α (rHuTNF-α) following our previous work. The rHuTNF-α was modified using activated polyethylene glycol (PEG), N-succinimidyl succinnate monomethoxy polyethylene glycol (SS-PEG). The pharmacokinetics and anti-tumor effect were investigated. The experimental results showed that PEGylated rHuTNF-α could obviously alter in vivo behavioral characteristics of rHuTNF-α. Among the synthesized PEG-rHuTNF-αs with different PEG molecules, PEG20000-rHuTNF-α demonstrated the longest circulating half-life (24.8 h) which was about 50 times longer than that of rHuTNF-α (28.8 min). In addition, there was much more PEG20000-rHuTNF-α distributed into tumor tissues than other PEG-rHuTNF-αs or rHuTNF-α with time, and PEG20000-rHuTNF-α also showed the highest anti-tumor potency. These results indicated that PEG20000-rHuTNF-α was a useful long circulating molecule with selective localization in tumor tissues and enhanced anti-tumor activity of rHuTNF-α.

PEGylated recombinant human tumor necrosis factor alpha: pharmacokinetics and anti-tumor effects.

Recent outbreaks of coronavirus have brought serious challenges to public health around the world, and it is essential to find effective treatments. In this study, the 3C-like proteinase (3CLpro) of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has been considered as an important drug target because of its role in viral replication. We initially optimized 251 compounds at the PM7 level of theory for docking with 3CLpro, and then we selected the top 12 compounds for further optimization with the B3LYP-D3/6-311G** method and obtained the top four compounds by further molecular docking. Quantum chemistry calculations were performed to predict molecular properties, such as the electrostatic potential and some CDFT descriptors. We also performed molecular dynamics simulations and free energy calculations to determine the relative stability of the selected four potential compounds. We have identified key residues controlling the 3CLpro/ligand binding from per-residue based decomposition of the binding free energy. Convincingly, the comprehensive results support the conclusion that the compounds have the potential to become a candidate for anti-coronavirus treatment.

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Exploration of plant-derived natural polyphenols toward COVID-19 main protease inhibitors: DFT, molecular docking approach, and molecular dynamics simulations

Xiu-Jian Gao

Papers

PEGylated PLGA nanoparticles as protein carriers: synthesis, preparation and biodistribution in rats

PEGylated polycyanoacrylate nanoparticles as tumor necrosis factor-α carriers

Stealth Polycyanoacrylate Nanoparticles as Tumor Necrosis Factor-α Carriers: Pharmacokinetics and Anti-tumor Effects

PEGylated recombinant human tumor necrosis factor alpha: pharmacokinetics and anti-tumor effects.

Exploration of plant-derived natural polyphenols toward COVID-19 main protease inhibitors: DFT, molecular docking approach, and molecular dynamics simulations