Julien Nicolas Profile picture
May 24, 2022 10 tweets 6 min read Read on X
🧵 Based on an analogy with AAm/Sty copolymers that exhibit #UCST properties we managed to replace Sty by aromatic ring-containing CKAs (MPDL & BMDO) to obtain degradable, UCST copolymers
✅Synthesis by #RAFT
✅UCST (w/ MDO = no UCST)
✅Degradation in accelerated conditions
1/9
The UCST can be finely tuned by simply varying the amount of CKA in the copolymer. With BMDO, Tcp = 22-55°C, thus covering r.t. and the body temperature, and opening the door to biomedical applications 💊 #hyperthermia 2/9
🔴 We also found that these copolymers can be rapidly degraded under "physiological" conditions (PBS, pH 7.4, 37°C) and even in water, below or above their UCST.

How fast❓ Faster than #PLA and even #PLGA!
▶️Up to -70% decrease in Mn after 7 days! 3/9
Why do we think this is so cool? It’s because CKA-containing copolymers have always suffered from slow hydrolytic degradation under physiological conditions, e.g. -70% decrease in Mn for OEGMA/MPDL copolymers after 12… months!
4/9
pubs.acs.org/doi/10.1021/ac…
Therefore, we believe that the AAm/CKA copolymerization system could open new exciting perspectives in the field of degradable vinyl polymers. 5/9

But there’s…
You can synthesize POEGMA-b-P(AAm-co-BMDO) amphiphilic diblock copolymers that exhibit both #UCST and #LCST transitions owing to the LCST of POEGMA, and the 3 different solubility states can be reversibly reached by oscillating the temperature (e.g., from 5 to 85°C). 6/9
📽
Icing on the cake: such copolymers can be formulated into degradable, #PEGylated, UCST nanoparticles by an *all-water* #nanoprecipitation process. Warm water poured into cold water, no organic solvent. 7/9 👇
✅The nanoparticles exhibit both UCST and LCST transitions
✅Their colloidal characteristics are reversible upon oscillating the temperature 8/9
Thanks for reading, hope you enjoyed the 🧵 !

And last but not least, the first author Amaury Bossion (poke @SardonL @DavidMecerreyes @POLYMAT_BERC) has recently found a permanent position at @Huntsman_Corp in Bruxelles! 🥳 9/9
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More from @julnicolas

Oct 4, 2022
Excited to share our work on subcutaneous administration of hydrophobic, vesicant anticancer drugs via water-soluble polymer prodrugs out in @J_A_C_S Wonderful team effort! @ERC_Research @UnivParisSaclay @CNRS @INC_CNRS @CNRSIdFSud @Pharma_UPSaclay doi.org/10.1021/jacs.2…
🧵1/n
👉 Chemotherapy is almost exclusively administered intravenously (IV) which has serious limitations:
➡️Patient discomfort (central route🩸, catheter failure…)
➡️Frequent hospital stays🏥, trained staff🩺👨‍⚕️needed…
➡️Costly (and cost will 📈 as new cancer cases will 📈)
🧵2/n
What about other administration routes?
➡️Oral route 💊: very restrictive. Low and variable bioavailability. Chemo requires precise dosing.
➡️Subcutaneous (SC) route 💉: not possible for vesicant/irritant drugs because of skin ulceration 🚨 and even necrosis ☠️
🧵3/n
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