A unique amphiphilic triblock copolymer, nontoxic to human blood and potential supramolecular drug delivery system for dexamethasone

The drug delivery system (DDS) often causes toxicity, triggering undesired cellular injuries. Thus, developing supramolecules used as DDS with tunable self-assembly and nontoxic behavior is highly desired. To address this, we aimed to develop a tunable amphiphilic ABA-type triblock copolymer that is nontoxic to human blood cells but also capable of self-assembling, binding and releasing the clinically used drug dexamethasone. We synthesized an ABA-type amphiphilic triblock copolymer (P2L) by incorporating tetra(aniline) TANI as a hydrophobic and redox active segment along with monomethoxy end-capped polyethylene glycol (mPEG2k; Mw = 2000 g mol−1) as biocompatible, flexible and hydrophilic part. Cell cytotoxicity was measured in whole human blood in vitro and lung cancer cells. Polymer-drug interactions were investigated by UV–Vis spectroscopy and computational analysis. Our synthesized copolymer P2L exhibited tuned self-assembly behavior with and without external stimuli and showed no toxicity in human blood samples. Computational analysis showed that P2L can encapsulate the clinically used drug dexamethasone and that drug uptake or release can also be triggered under oxidation or low pH conditions. In conclusion, copolymer P2L is nontoxic to human blood cells with the potential to carry and release anticancer/anti-inflammatory drug dexamethasone. These findings may open up further investigations into implantable drug delivery systems/devices with precise drug administration and controlled release at specific locations.

ACID-LABILE CORE CROSS-LINKED MICELLES FOR pH-TRIGGERED RELEASE OF DOXORUBICIN

A acid-labile core cross-linked micelle system of amphiphilic triblock copolymer of poly(oligo(ethylene glycol) methyl ether methacrylate)-block-poly(styrene-alt-maleic anhydride)-block-poly(styrene) (POEGMA-b-PSMA-b-PS) was prepared. The POEGMA-b-PSMA-b-PS triblock copolymers were synthesized by the reversible addition-fragmentation chain transfer (RAFT) polymerization. Doxorubincin (DOX) was entrapped into micellar structure with POEGMA block as a shell and PSMA-b-PS block as a core. Then, core cross-linking was carried out by amidation reaction between 2,2-bis(aminoethoxy)propane and maleic anhydride group inner core. DOX loading content and efficiency were calculated to be 18 and 90 (wt. %), respectively. Core cross-linked micelles illustrated good stability under physiological condition but disassociated rapidly under acidic pH. The DOX release experiments indicated a rapid DOX release at pH 5.0 compared to pH 7.4.

ABA Type Amphiphiles with Poly(2-Benzhydryl-2-Oxazine) Moieties: Synthesis, Characterization and Inverse Thermogelation

<div>Thermoresponsive polymers are frequently discussed for various applications. Here, we introduce a novel amphiphilic triblock copolymer, which undergoes inverse thermogelation, i.e. is forms a physical gel upon cooling. The polymers comprises poly(2-benzhydryl-2-oxazine) as the hydrophobic building block, a polymer which has not been reported to date. The physical gels are surprisingly strong with a storage modulus of 22 kPa at 25 wt.% in water. In addition, relatively high yield and flow points were determined by rheology.</div>

ABA Type Amphiphiles with Poly(2-Benzhydryl-2-Oxazine) Moieties: Synthesis, Characterization and Inverse Thermogelation

<div>Thermoresponsive polymers are frequently discussed for various applications. Here, we introduce a novel amphiphilic triblock copolymer, which undergoes inverse thermogelation, i.e. is forms a physical gel upon cooling. The polymers comprises poly(2-benzhydryl-2-oxazine) as the hydrophobic building block, a polymer which has not been reported to date. The physical gels are surprisingly strong with a storage modulus of 22 kPa at 25 wt.% in water. In addition, relatively high yield and flow points were determined by rheology.</div>

Potential Effects of Poloxamer 188 on Rat Isolated Brain Mitochondria after Oxidative Stress In Vivo and In Vitro

Outcome after cerebral ischemia is often dismal. Reperfusion adds significantly to the ischemic injury itself. Therefore, new strategies targeting ischemia/reperfusion (I/R) injury are critically needed. Poloxamer (P)188, an amphiphilic triblock copolymer, is a highly promising pharmacological therapeutic as its capability to insert into injured cell membranes has been reported to protect against I/R injury in various models. Although mitochondrial function particularly profits from P188 treatment after I/R, it remains unclear if this beneficial effect occurs directly or indirectly. Here, rat isolated brain mitochondria underwent oxidative stress in vivo by asphyxial cardiac arrest or in vitro by the addition of hydrogen peroxide (H2O2) after isolation. Mitochondrial function was assessed by adenosine triphosphate synthesis, oxygen consumption, and calcium retention capacity. Both asphyxia and H2O2 exposure significantly impaired mitochondrial function. P188 did not preserve mitochondrial function after either injury mechanism. Further research is indicated.

Synthesis of nanostructured silica/hydroxyapatite hybrid particles containing amphiphilic triblock copolymer for effectively controlling hydration layer structures with cytocompatibility

This is the first successful report to synthesize the nanostructured mesoporous silica (MS)/hydroxyapatite (HA) hybrid particles containing amphiphilic triblock copolymer. The controlled hydration layer structures on the hybrid particles significantly affected the protein secondary structures for providing the higher cytocompatibility.