Oral administration is the most commonly used and readily accepted form of drug delivery; however, it is find that many drugs are difficult to attain enough bioavailability when administered via this route. Polymeric micelles (PMs) can overcome some limitations of the oral delivery acting as carriers able to enhance drug absorption, by providing (1) protection of the loaded drug from the harsh environment of the GI tract, (2) release of the drug in a controlled manner at target sites, (3) prolongation of the residence time in the gut by mucoadhesion, and (4) inhibition of efflux pumps to improve the drug accumulation. To explain the mechanisms for enhancement of oral bioavailability, we discussed the special stability of PMs, the controlled release properties of pH-sensitive PMs, the prolongation of residence time with mucoadhesive PMs, and the P-gp inhibitors commonly used in PMs, respectively. The primary purpose of this paper is to illustrate the potential of PMs for delivery of poorly water-soluble drugs with bioavailability being well maintained.

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Polymeric Micelles, a Promising Drug Delivery System to Enhance Bioavailability of Poorly Water-Soluble Drugs

D-ɑ-tocopheryl polyethylene glycol succinate (Vitamin E TPGS or TPGS) has been approved by FDA as a safe adjuvant and widely used in drug delivery systems. The biological and physicochemical properties of TPGS provide multiple advantages for its applications in drug delivery like high biocompatibility, enhancement of drug solubility, improvement of drug permeation and selective antitumor activity. Notably, TPGS can inhibit the activity of ATP dependent P-glycoprotein and act as a potent excipient for overcoming multi-drug resistance (MDR) in tumor. In this review, we aim to discuss the recent advances of TPGS in drug delivery including TPGS based prodrugs, nitric oxide donor and polymers, and unmodified TPGS based formulations. These potential applications are focused on enhancing delivery efficiency as well as the therapeutic effect of agents, especially on overcoming MDR of tumors. It also demonstrates that the clinical translation of TPGS based nanomedicines is still faced with many challenges, which requires more detailed study on TPGS properties and based delivery system in the future.

Recent Advances in the Application of Vitamin E TPGS for Drug Delivery.

Chitosan oligosaccharide (COS): An overview

A nanocarrier system of d-a-tocopheryl polyethylene glycol 1000 succinate (TPGS)-functionalized polydopamine-coated mesoporous silica nanoparticles (NPs) is developed for sustainable and pH-responsive delivery of doxorubicin (DOX) as a model drug for the treatment of drug-resistant nonsmall cell lung cancer. Such nanoparticles are of desired particle size, drug loading, and drug release profile. The surface morphology, surface charge, and surface chemical properties are also successfully characterized by a series of techniques such as transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), Brunauer-Emmett-Teller (BET) method, thermal gravimetric analysis (TGA), dynamic light scattering (DLS), and Fourier transform infrared spectroscopy (FTIR). The normal A549 cells and drug-resistant A549 cells are employed to access the cytotoxicity and cellular uptake of the NPs. The therapeutic effects of TPGS-conjugated nanoparticles are evaluated in vitro and in vivo. Compared with free DOX and DOX-loaded NPs without TPGS ligand modification, MSNs-DOX@PDA-TPGS exhibits outstanding capacity to overcome multidrug resistance and shows better in vivo therapeutic efficacy. This splendid drug delivery platform can also be sued to deliver other hydrophilic and hydrophobic drugs.

TPGS-Functionalized Polydopamine-Modified Mesoporous Silica as Drug Nanocarriers for Enhanced Lung Cancer Chemotherapy against Multidrug Resistance.

Vitamin E-based nanomedicines for anti-cancer drug delivery

The applications of Vitamin E TPGS in drug delivery.

To overcome the P-glycoprotein (P-gp)-induced multidrug resistance (MDR) of cancer cells, a novel copolymer, chitosan-graft-D-α-tocopheryl polyethylene glycol 1000 (TPGS) (CT) was synthesized for doxorubicin (DOX) delivery by the P-gp inhibiting virtue of TPGS. DOX-loaded CT nanoparticles (NPs) were fabricated by a modified solvent extraction/evaporation method combined with ionic cross-linking to form a uniform particle size of 140-180 nm with ∼40% DOX loading efficiency. These drug-loaded CT NPs demonstrated a pH-responsive release behavior, and DOX was released more quickly under low pH values. Significant cell cytotoxicity was observed on the human hepatocarcinoma cells (HepG2 and BEL-7402) and human breast adenocarcinoma cells (MCF-7). The cell cytotoxicity and apoptosis of drug-resistant cells (MCF-7/DOX and BEL-7402/5-Fu), was greatly enhanced as compared to Adriamycin. The IC50 value showed that DOX-loaded CT NPs could be 1.5-199-fold more effective than Adriamycin. This can be attributed to the P-gp blocking and down-regulation of ATP levels by the CT NPs. The potential of these NPs to act as an oral delivery system was also investigated. Both the pharmacokinetic properties and in vivo antitumor activity of DOX-loaded CT NPs were improved compared with Adriamycin.

Chitosan-g-TPGS nanoparticles for anticancer drug delivery and overcoming multidrug resistance.

Abstract Industrial activities and increased human population have made wastewater streams not entirely amenable to conventional treatment methods. Anaerobic digestion (AD) can treat such wastewaters with the advantage of bioresource recovery. However, the presence of solids and recalcitrant compounds in most wastewater streams may affect the AD process. Thus, combining AD with advanced oxidation processes (AOPs) such as ozonolysis is necessary. Ozonolysis can improve the biodegradability of wastewater substrates or eliminate biorecalcitrant pollutants that escape the AD process. This study combined ozonolysis with AD to treat waste activated sludge (WAS) and distillery wastewater (DWW). When applied as a pre-treatment, ozonolysis caused the rigid cell walls in WAS to rupture and solubilised the extracellular polymeric substances (EPS), leading to increased biodegradability. For the DWW, ozonolysis pre-treatment reduced the biorecalcitrant aromatic compounds to simple aliphatic compounds, thereby increasing biodegradability. In the ensuing anaerobic process, the WAS pre-treatment improved TSS and COD reductions and a 230% increase in cumulative biogas production. For the DWW, the ozonolysis pre-treatment did not significantly impact COD reduction or biogas production; however, ozonolysis as a post-treatment removed the color causing biorecalcitrant melanoidins from the anaerobically digested effluent and solubilised the sludge (TSS) washed out from the AD unit. Therefore, the AD-ozonolysis process configuration depends on the substrate being treated. Ozonolysis is best applied pre-AD for WAS treatment and post-AD for DWW.

Ben Oketch Otieno

Papers

The applications of Vitamin E TPGS in drug delivery.

Chitosan-g-TPGS nanoparticles for anticancer drug delivery and overcoming multidrug resistance.

Process configuration of combined ozonolysis and anaerobic digestion for wastewater treatment