Cooling-Triggered Release from Mesoporous Poly(N-isopropylacrylamide) Microgels at Physiological Conditions

Abstract

Poly( N -isopropylacrylamide) (pNIPAM) hydrogels have broad potential applications as drug delivery vehicles because of their thermoresponsive behavior. pNIPAM loading/release performances are directly affected by the gel network structure. Therefore, there is a need with the approaches for accurate design of 3D pNIPAM assemblies with the structure ordered at the nanoscale. This study demonstrates size-selective spontaneous loading of macromolecules (dextrans 10−500 kDa) into pNIPAM microgels by microgel heating from 22 to 35 °C (microgels collapse and trap dextrans) followed by the dextran release upon further cooling down to 22 °C (microgels swell back) . This temperature-mediated behavior is fully reversible. The structure of pNIPAM microgels was tailored via hard templating and cross-linking of the hydrogel using sacrificial mesoporous cores of vaterite CaCO 3 microcrystals. In addition, the fabrication of hollow thermoresponsive pNIPAM microshells has been demonstrated, utilizing vaterite microcrystals that had narrower pores. The proposed approach for heating-triggered encapsulation and cooling-triggered release into/from pNIPAM microgels may pave the ways for applications of pNIPAM hydrogels for skin and transdermal cooling-responsive drug delivery in the future.

Modulation of phase transition of poly(N‐isopropylacrylamide)‐based microgels for pulsatile drug release

“…A similar process is followed for the loading of curcumin in ethanol. The entrapment efficiency (EE) and loading amount (LA) were calculated according to Equation 1 and the previously made calibration curves (Figure S4), where C and C m represent the concentration of drug and microgel respectively 24 : Its structure was verified by 1 H NMR, and all the peaks have been well assigned in Figure 2. The molecular weight of HPEG is 2400 Da, therefore, the chain length of the polyalanine can be determined by comparing the integration of methyl protons in Ala x at 2.1 ppm with that of methylene protons of HPEG at 4.4 ppm.…”

Thermocontrolled Reversible Enzyme Complexation-Inactivation-Protection by Poly(N-acryloyl glycinamide)

“…Focused on biological approaches, we used physiological buffer system, namely potassium phosphate buffer, pH 7.4. Of course, our model system with phase-transition temperature lower than 25 °C looks to be not optimal for medicinal usage, although some tasks, including skin delivery, allow for system formulation in a very wide temperature range due to a high ability to cooling without the occurrence of undesired side effects [ 29 , 30 ]. Regardless, the temperature of phase transition of PNAGA-based polymers can be tuned in a wide range by copolymerization or by adjusting the molar mass or end-groups [ 31 , 32 , 33 , 34 , 35 ].…”

Biopolymer-Based Multilayer Capsules and Beads Made via Templating: Advantages, Hurdles and Perspectives

“…Furthermore, through the use of thermo-responsive polymers, temperature-controlled shrinkage/swelling of pure polymeric particles can be achieved [190]. Recently reported, through the use of vaterite-templated poly(N-isopropylacrylamide) microgels, the temperature-controlled release of macromolecular drugs was demonstrated [191]. Ionic strength-and pH-induced swelling/shrinkage was also reported in gelatin-based microgels templated upon CaCO 3 crystals [192].…”