In Vivo Biocompatible Self-Assembled Nanogel Based on Hyaluronic Acid for Aqueous Solubility and Stability Enhancement of Asiatic Acid

Abstract

Asiatic acid (AA), a natural triterpene found in Centalla asiatica, possesses polypharmacological properties that can contribute to the treatment and prophylaxis of various diseases. However, its hydrophobic nature and rapid metabolic rate lead to poor bioavailability. The aim of this research was to develop a thermoresponsive nanogel from hyaluronic acid (HA) for solubility and stability enhancement of AA. Poly(N-isopropylacrylamide) (pNIPAM) was conjugated onto HA using a carbodiimide reaction followed by 1H NMR characterization. pNIPAM-grafted HA (HA-pNIPAM) nanogels were prepared with three concentrations of polymer, 0.1, 0.15 and 0.25% w/v, in water by the sonication method. AA was loaded into the nanogel by the incubation method. Size, morphology, AA loading capacity and encapsulation efficiency (EE) were analyzed. In vitro cytocompatibility was evaluated in fibroblast L-929 cells using the PrestoBlue assay. Single-dose toxicity was studied using rats. HA-pNIPAM nanogels at a 4.88% grafting degree showed reversible thermo-responsive behavior. All nanogel formulations could significantly increase AA water solubility and the stability was higher in nanogels prepared with high polymer concentrations over 180 days. The cell culture study showed that 12.5 µM AA in nanogel formulations was considered non-toxic to the L-929 cells; however, a dose-dependent cytotoxic effect was observed at higher AA-loaded concentrations. In vivo study proved the non-toxic effect of AA loaded in HA-pNIPAM nanogels compared with the control. Taken together, HA-pNIPAM nanogel is a promising biocompatible delivery system both in vitro and in vivo for hydrophobic AA molecules.

Multi-Stimuli-Responsive and Cell Membrane Camouflaged Aggregation-Induced Emission Nanogels for Precise Chemo-photothermal Synergistic Therapy of Tumors

“…The hydrophobic AIE molecules (TN) can be encapsulated in the nanogel structure through hydrophobic interaction. 74 The cross-linked network structure of nanogels would be occupied and expanded by the loaded TN with the long alkyl chain and large planar (NDTA core) structure, presumably resulting in an increase in nanogel size after loading TN. The average hydrodynamic diameters of PNA nanogels at pH 7.4 and pH 5.0 were 184 and 157 nm and increased to 259 and 226 nm after encapsulation of TN and Dox as well as cell membrane enveloping (P-TN-Dox@CM).…”

“…As displayed in Figure e, the stepwise altered hydrodynamic diameters indicated successful functionalization of nanogels. The hydrophobic AIE molecules (TN) can be encapsulated in the nanogel structure through hydrophobic interaction . The cross-linked network structure of nanogels would be occupied and expanded by the loaded TN with the long alkyl chain and large planar (NDTA core) structure, presumably resulting in an increase in nanogel size after loading TN.…”

Assessing the In Vivo Biocompatibility of Molecularly Imprinted Polymer Nanoparticles

“…NanoMIPs were administered orally in groups OR-100 and OR-200 at two dilutions, 100 µg mL −1 and 200 µg mL −1 respectively. In both cases, the nanoMIPs were administered as a 300 µL solution in PBS, resulting in doses of either 200 or 400 µg kg −1 body weight, similar in dosage to previous in vivo studies on polyNIPAm nanoparticles [ 20 , 21 ]. These experiments were designed to determine biodistribution, clearance and cytotoxic properties of the nanoMIPs.…”

Nanofertilizers: Types, Delivery and Advantages in Agricultural Sustainability

“…Regardless, it is crucial to consider the specific needs of the plants and the local environment before choosing the most appropriate nanofertilizer. Carbon-based promote plant growth, increase water and nutrient retention, help during drought [46] time consuming synthesis methods [47] Chitosan-based biodegradable, adjustable in size, easy to modify, protect biomolecules from environmental factors [48,49] hydrophilicity, weak mechanical properties, low gas permeability, low encapsulation efficiency [50] Clay-based large surface area, nanolayer reactivity, regulate the release of anions [51] can inhibit leaf growth and transpiration [52] Nanocapsule-based controlled nutrient release, efficient nutrient delivery, reduced risk of leaching [53,54] require complex synthesis processes, subject to material limitations Nanogel-based highly soluble, biodegradable, non-toxic, improves water retention [55] limitations regarding the optimization of biodistribution, degradation mechanism, and component toxicity [56] Polyurethane-based controlled nutrient release, improved water-holding capacity, reduced soil erosion [57] weak chemical and thermal stability, rapid elimination, lower polymer life span due to the formation of acid monomers in polymer matrix [58] Starch-based renewable energy source, effective nutrient delivery, minimal chemical waste [59] expensive and time-consuming, unstable nature [60] Zeolite-based improved nutrient delivery, tailored nutrient provision, reduced fertilization cost [45,61] require specific formulations and synthesis processes for optimal results, not useful in the management of anionic nutrients and need to be complemented with biopolymers and biopolymer complexes [62] 2.1.2. Nanofertilizers for Targeted Delivery Nanoaptamers Nanoaptamers belong to an innovative new form of fertilizer delivery system revolutionizing agricultural cultivation.…”