HPMA‐PEG Surfmers and Their Use in Stabilizing Fully Biodegradable Polymer Nanoparticles

Abstract

The most adopted methods to produce polymer nanoparticles (NPs) for medical and pharmaceutical applications use surfactants that are toxic and physically adsorbed to the NPs, with the risk of desorption and insurgence of side effects. A valid alternative is represented by the use of surfmers, reactive surfactants that are chemically linked to the polymer chains, thus avoiding the release of toxic species. In this case, the lack of biodegradable surfmers introduces the concern of polymer accumulation into the body. In this work, biodegradable, poly(ethylene glycol) (PEG)ylated N‐(2‐hydroxypropyl) methacrylamide (HPMA) based surfmers are synthesized and used to stabilize lipophilic NPs. In particular, the NP core is made from a macromonomer comprising a poly(lactic acid) (PLA) chain functionalized with HPMA double bond. The NP forming polymer chains are then constituted by a uniform poly(HPMA) backbone that is biocompatible and water soluble and hydrolysable PEG and PLA pendants assuring the complete degradability of the polymer. The stability provided to these NPs by the synthesized surfmers is studied in the cases of both emulsion free radical polymerization and solution free radical polymerization followed by the flash nanoprecipitation of the obtained amphiphilic copolymers.

Self‐Assembling PCL‐Based Nanoparticles as PTX Solubility Enhancer Excipients

“…In this way, in contrast to what happens for the common linear PCL‐PEG block‐copolymers, it is possible to control not only the length of the polyester portion, but also the number of the biodegradable lateral chains paving the way to a higher tunability of the system in terms of self‐assembling behavior, NP size, and NP degradation time . In particular, in order to avoid the storage issue of the NPs and the complex process of synthesis (e.g., T‐mixer), a new method for the NP formation that requires only a syringe and a filter syringe was adopted. This important feature has been achieved via the synthesis of a block‐copolymer in which the lipo/hydrophilic balance has been optimized in order to: i) stabilize the NPs, ii) efficiently entrap the drug, and iii) degrade leaving nontoxic and water‐soluble compounds.…”

Influence of the Polymer Microstructure over the Phase Separation of Thermo-Responsive Nanoparticles

“…It is worth noticing that the Tcp is independent from p for all the n considered ( Table 1 ). In fact, the high conversions obtained in the synthesis of the stabilizer coupled with the high compartmentalization achievable with the RAFT emulsion polymerization permits to obtain a library of NPs with a transition temperature that is dependent only on the thermo-responsive monomer chosen [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ].…”

“…In the last decades, this limitation was progressively overcome by the advent of controlled radical polymerizations, which gave new lymph to the field [ 13 , 14 , 15 ]. In particular, the high control over the polymer chain microstructure achievable with these polymerization techniques paved the way to highly engineered colloids [ 16 , 17 , 18 , 19 , 20 , 21 , 22 ], contributing to the spreading of the NP technology towards previously unexplored applications.…”

Poly(HPMA)-based copolymers with biodegradable side chains able to self assemble into nanoparticles

“…The HPMA was synthesized following a procedure reported in literature. 14 Briey, 25.22 g (238 mmol) of sodium carbonate were suspended in 56 mL of anhydrous dichloromethane (DCM). The temperature was kept at À10 C using a brine\ice mixture and 16.25 g (216 mmol) of DL-1-amino-2-propanol were added.…”