Drug delivery of 6-bromoindirubin-3’-glycerol-oxime ether employing poly(d,l-lactide-co-glycolide)-based nanoencapsulation techniques with sustainable solvents

Background Insufficient solubility and stability of bioactive small molecules as well as poor biocompatibility may cause low bioavailability and are common obstacles in drug development. One example of such problematic molecules is 6-bromoindirubin-3'-glycerol-oxime ether (6BIGOE), a hydrophobic indirubin derivative. 6BIGOE potently modulates the release of inflammatory cytokines and lipid mediators from isolated human monocytes through inhibition of glycogen synthase kinase-3 in a favorable fashion. However, 6BIGOE suffers from poor solubility and short half-lives in biological aqueous environment and exerts cytotoxic effects in various mammalian cells. In order to overcome the poor water solubility, instability and cytotoxicity of 6BIGOE, we applied encapsulation into poly(d,l-lactide-co-glycolide) (PLGA)-based nanoparticles by employing formulation methods using the sustainable solvents Cyrene™ or 400 g/mol poly(ethylene glycol) as suitable technology for efficient drug delivery of 6BIGOE. Results For all preparation techniques the physicochemical characterization of 6BIGOE-loaded nanoparticles revealed comparable crystallinity, sizes of about 230 nm with low polydispersity, negative zeta potentials around − 15 to − 25 mV, and biphasic release profiles over up to 24 h. Nanoparticles with improved cellular uptake and the ability to mask cytotoxic effects of 6BIGOE were obtained as shown in human monocytes over 48 h as well as in a shell-less hen’s egg model. Intriguingly, encapsulation into these nanoparticles fully retains the anti-inflammatory properties of 6BIGOE, that is, favorable modulation of the release of inflammation-relevant cytokines and lipid mediators from human monocytes. Conclusions Our formulation method of PLGA-based nanoparticles by applying sustainable, non-toxic solvents is a feasible nanotechnology that circumvents the poor bioavailability and biocompatibility of the cargo 6BIGOE. This technology yields favorable drug delivery systems for efficient interference with inflammatory processes, with improved pharmacotherapeutic potential. Graphical Abstract

Using Sound to Synthesize Covalent Organic Frameworks in Water

Most covalent organic frameworks (COFs) are synthesized using solvothermal conditions (>120 °C, >72 h) in harmful organic solvents. We report a strategy for rapidly synthesizing imine-linked COFs (< 60 min) in aqueous acetic acid using sonochemistry, avoiding most of the downsides of solvothermal methods. We first synthesized seven known COFs using this method and obtained crystallinity and porosity comparable to or better than materials from previously reported solvothermal routes. This sonochemical method even works in highly sustainable solvents, such as food-grade vinegar. The generality of the method was demonstrated by preparing two unreported COFs. Finally, we showed that one sonochemical COF is an excellent photocatalyst for sacrificial hydrogen evolution from water with a more sustained catalytic performance than its solvothermal analog. The speed, ease and generality of this sonochemical method with no sacrifice in material quality makes it an enabling methodology for rapid discovery of new functional COF materials.

Using Sound to Synthesize Covalent Organic Frameworks in Water

Most covalent organic frameworks (COFs) are synthesized using solvothermal conditions (>120 °C, >72 h) in harmful organic solvents. We report a strategy for rapidly synthesizing imine-linked COFs (< 60 min) in aqueous acetic acid using sonochemistry, avoiding most of the downsides of solvothermal methods. We first synthesized seven known COFs using this method and obtained crystallinity and porosity comparable to or better than materials from previously reported solvothermal routes. This sonochemical method even works in highly sustainable solvents, such as food-grade vinegar. The generality of the method was demonstrated by preparing two unreported COFs. Finally, we showed that one sonochemical COF is an excellent photocatalyst for sacrificial hydrogen evolution from water with a more sustained catalytic performance than its solvothermal analog. The speed, ease and generality of this sonochemical method with no sacrifice in material quality makes it an enabling methodology for rapid discovery of new functional COF materials.

Green Chemistry Approach for Fabrication of Polymer Composites

Solvents are an inevitable part of industries. They are widely used in manufacturing and processing industries. Despite the numerous controlling measures taken, solvents contaminate our environment to a vast extent. Green and sustainable solvents have been a matter of growing interest within the research community over the past few years due to the increasing environmental concerns. Solvents are categorized as “green” based on their nonvolatility, nonflammability, availability, biodegradability and so on. The use of ionic liquids, super critical carbon dioxide and aqueous solvents for the fabrication of polymer composites is discussed in this review. The progress of utilizing solvent-free approaches for polymer composite preparation and efforts to produce new biobased solvents are also summarized.