Engineered Polymersomes for the Treatment of Fish Odor Syndrome: A First Randomized Double Blind Olfactory Study

Abstract

Trimethylamine (TMA) is a metabolite overtly present in patients suffering from trimethylaminuria (TMAU), a rare genetic disorder characterized by a strong “fishy” body odor. To date, no approved pharmacological treatment to sequester excess TMA on the skin of patients exists. Here, transmembrane pH gradient poly(isoprene)‐block‐poly(ethylene glycol) (PI‐b‐PEG) polymersomes are investigated for the topical removal of TMA. PI‐b‐PEG amphiphiles of varying chain length are synthesized and evaluated for their ability to form vesicular structures in aqueous media. The optimization of the PI/PEG ratio of transmembrane pH gradient polymersomes allows for the rapid and efficient capture of TMA both in solution and after incorporation into a topical hydrogel matrix at the pH of the skin. A subsequent double blind olfactory study reveals a significant decrease in perceived odor intensity after application of the polymersome‐based formulation on artificial skin substrates that has been incubated in TMA‐containing medium. This simple and novel approach has the potential to ease the burden of people suffering from TMAU.

Ammonia uptake by transmembrane pH gradient poly(isoprene)-block-poly(ethylene glycol) polymersomes

“…For PI-b-PEG 2000 , encapsulation experiments were reported previously and the data confirmed a vesicle structure for PI-b-PEG 2000 with PI/PEG (w/w) ratios of 1.32 to 2.90. 29 Encapsulation experiments with PI-b-PEG 700 indirectly revealed a high proportion of hollow structures (Fig. S21, ESI †), supporting the elevated ammonia capture values at high PI/PEG 700 (w/w) ratios.…”

“…The synthesis of several polymers of the PEG 2000 library is reported in a previous publication from our group (i.e., polymers with PI/PEG 2000 (w/w) ratios of 1.32, 1.99, 2.30, 2.90, and 3.62). 29 Synthesis of PEG monomethyl ether 2-bromopropionate (PEG-Br) (3). PEG monomethyl ether (1) (1 eq.)…”

“…Recently, our group described the formation of transmembrane pH gradient polymersomes comprised of PI-b-PEG block copolymers, that were able to capture the metabolite trimethylamine (TMA), showing promise for the topical symptomatic treatment of trimethylaminuria. 29 Employing the optimized conditions found in this previous study, we attempted to prepare vesicles with our amphiphiles having an inside pH of 2.0 using an emulsification process. 23 Sizes of macromolecular assemblies were analyzed by DLS.…”

Mastering the Tools: Natural versus Artificial Vesicles in Nanomedicine

“…In-human olfactory studies Sequestration of trimethylamine (TMA) via polymersome transmembrane pH gradient for trimethylaminuria treatment [ 274] Polymersomes of the diblock copolymer PS-b-PIAT…”

“…In addition, they demonstrated that polymersomes conjugated with the transactivator of transcription cell-penetrating peptide (derived from HIV virus) may increase their cellular uptake in vitro. [230] Similarly to liposomes, the hydrogel formulations for polymersomes are based on synthetic [272][273] or natural polymers [274][275] (see Table 1), combining polymersome membrane integrity with sustained cargo release.…”