Thermoresponsive nanogels based on polyelectrolyte complexes between polycations and functionalized hyaluronic acid

Colloidal Polyelectrolyte Complexes from Hyaluronic Acid: Preparation and Biomedical Applications

“…Le et al reported that HA/PLL PEC particles with PLL in excess ( n –/ n + < 1) are stable against HAase, which is attributed to the protective effect of PLL on the particle surface. [ 23 ] More interestingly, HA‐based nanostructures may not only be stable against HAase but also inhibit this enzyme from degrading free HA, as reported by Duan et al with micelles from HA grafted with poly(γ‐benzyl ‐l‐ glutamate) as a potential HAase inhibitor for biomedical applications. [ 181 ] Therefore, HAase‐induced degradation should not be generalized for all HA‐based colloidal PECs and needs to be evaluated case by case, which can verify their potential as a HAase‐responsive system for tumor targeting or a HAase‐inhibiting agent.…”

“…[50] In order to limit the precipitation of such hydrophobic drugs and maintain their molecular state in a sufficient time during the complexation or the co-incubation for an effective inclusion of drug molecules in PEC particles, organic cosolvents like ethanol or acetone can be used, which should be thereafter removed by evaporation or dialysis. [23,50] Specifically, to encapsulate hydrophobic bioactive polyphenols like CUR and quercetagetin in HA/zein PECs, the complexation should take place in an ethanol-water mixture due to the low aqueous solubility of both zein and the active compounds, followed by ethanol evaporation in order to obtain the final drug-loaded PECs (antisolvent coprecipitation method, Figure 5). [37][38][39]109] For PECs from HA and proteins, encapsulation of a hydrophobic drug like CUR can also be improved with an adequate NaCl concentration due to enhanced hydrophobic force with "salting-out" effect, as reported for colloidal PECs from HA and WPI.…”

“…[33] The amphiphilic PEO-PPO grafts on constituent polymers can also stabilize PEC particles against physiological ionic strength through supplementary intraparticle hydrophobic interactions. [23] Moreover, when prepared from thiol-disposing polymers, for example, HA-SH, PLL-SH, or feather keratin, PEC particles can be further stabilized by self-crosslinking though the formation of the cleavable disulfide bonds as a result of redox reaction between thiol groups, either spontaneously with oxygen readily present in the media or more favorably upon adding an oxidizing agent like hydroxy peroxide, which may ultimately enhance drug encapsulation and PEC stability against high ionic strength. [27,32,41] Regarding drug release, PECs can offer a controlled release which follows an initial burst release phase and might depend on the studied pH.…”

“…[ 74 ] Concerning the relative arrangement between two complexing polyelectrolytes, Le et al reported that HA forms more stable PECs with PLL than with DEAE‐D, as both HA and PLL have their charges distributed evenly on the polymer chains, which may allow more optimal ion‐pairing than in the case of HA/DEAE‐D PECs, where DEAE‐D has random charge distribution. [ 23 ] It should be noted that since biopolymers usually have weak charges, their ionization rate also depends on media pH. A change in pH may lead to an increase in ionization rate, therefore higher charge density as well as enhance the rigidity of polymer chains and increase thus the yield or particle size of resulting PECs, or vice versa.…”

“…[ 44 ] By using HA functionalized with thermosensitive amphiphilic polyethers, that is, poly(ethylene oxide)‐ co ‐poly(propylene oxide) (PEO‐PPO), Le et al also found that the encapsulation of CUR in PECs can be improved by controlling complexation temperature. [ 23 ] Covalent conjugation of drug molecules on parent polymers of PECs as prodrugs instead of physical entrapment method can also improve drug solubility and encapsulation, pharmacokinetic properties, and therapeutic efficacy while reducing their systemic side effects, for example, HA/CTS PECs with covalently bonded gemcitabine and platinum (IV) on HA and CTS respectively [ 46 ] or with docetaxel grafted on HA. [ 47 ] Another finding worth mentioning is that for HA/CTS PECs loaded with tocopherol (also known as vitamin E), which is a lipophilic compound, using TPP for further particle stabilization as mentioned in Section 3.3.6 can lead to particles having a better controlled structure but may reduce the encapsulation rate of tocopherol.…”