Curcumin Loaded PEGylated Nanoemulsions Designed for Maintained Antioxidant Effects and Improved Bioavailability: A Pilot Study on Rats

The current study describes the experimental design guided development of PEGylated nanoemulsions as parenteral delivery systems for curcumin, a powerful antioxidant, as well as the evaluation of their physicochemical characteristics and antioxidant activity during the two years of storage. Experimental design setup helped development of nanoemulsion templates with critical quality attributes in line with parenteral application route. Curcumin-loaded nanoemulsions showed mean droplet size about 105 nm, polydispersity index <0.15, zeta potential of −40 mV, and acceptable osmolality of about 550 mOsm/kg. After two years of storage at room temperature, all formulations remained stable. Moreover, antioxidant activity remained intact, as demonstrated by DPPH (IC50 values 0.078–0.075 mg/mL after two years) and FRAPS assays. In vitro release testing proved that PEGylated phospholipids slowed down the curcumin release from nanoemulsions. The nanoemulsion carrier has been proven safe by the MTT test conducted with MRC-5 cell line, and effective on LS cell line. Results from the pharmacokinetic pilot study implied the PEGylated nanoemulsions improved plasma residence of curcumin 20 min after intravenous administration, compared to the non-PEGylated nanoemulsion (two-fold higher) or curcumin solution (three-fold higher). Overall, conclusion suggests that developed PEGylated nanoemulsions present an acceptable delivery system for parenteral administration of curcumin, being effective in preserving its stability and antioxidant capacity at the level highly comparable to the initial findings.

Transcriptomic and morphological response of SIM-A9 mouse microglia to carbon nanotube neuro-sensors

Single-walled carbon nanotubes (SWCNT) are used in neuroscience for deep-brain imaging, neuron activity recording, measuring brain morphology, and imaging neuromodulation. However, the extent to which SWCNT-based probes impact brain tissue is not well understood. Here, we study the impact of (GT)6-SWCNT dopamine nanosensors on SIM-A9 mouse microglial cells and show SWCNT-induced morphological and transcriptomic changes in these brain immune cells. Next, we introduce a strategy to passivate (GT)6-SWCNT nanosensors with PEGylated phospholipids to improve both biocompatibility and dopamine imaging quality. We apply these passivated dopamine nanosensors to image electrically stimulated striatal dopamine release in acute mouse brain slices, and show that slices labeled with passivated nanosensor exhibit higher fluorescence response to dopamine and measure more putative dopamine release sites. Hence, this facile modification to SWCNT-based dopamine probes provides immediate improvements to both biocompatibility and dopamine imaging functionality with an approach that is readily translatable to other SWCNT-based neurotechnologies.

Antibody-Hapten Recognition at the Surface of Functionalized Liposomes Studied by SPR: Steric Hindrance of Pegylated Phospholipids in Stealth Liposomes Prepared for Targeted Radionuclide Delivery

Targeted PEGylated liposomes could increase the amount of drugs or radionuclides delivered to tumor cells. They show favorable stability and pharmacokinetics, but steric hindrance of the PEG chains can block the binding of the targeting moiety. Here, specific interactions between an antihapten antibody (clone 734, specific for the DTPA-indium complex) and DTPA-indium-tagged liposomes were characterized by surface plasmon resonance (SPR). Non-PEGylated liposomes fused on CM5 chips whereas PEGylated liposomes did not. By contrast, both PEGylated and non-PEGylated liposomes attached to L1 chips without fusion. SPR binding kinetics showed that, in the absence of PEG, the antibody binds the hapten at the surface of lipid bilayers with the affinity of the soluble hapten. The incorporation of PEGylated lipids hinders antibody binding to extents depending on PEGylated lipid fraction and PEG molecular weight. SPR on immobilized liposomes thus appears as a useful technique to optimize formulations of liposomes for targeted therapy.

Camptothecin in Sterically Stabilized Phospholipid Nano-Micelles: A Novel Solvent pH Change Solubilization Method

Camptothecin (CPT) is a topoisomerase I inhibitor that acts against a broad spectrum of cancers. Unfortunately clinical application of CPT is limited by insolubility, instability, and toxicity problems. To circumvent these delivery problems of CPT, we propose biocompatible, targeted sterically stabilized micelles (SSM) as nanocarriers for CPT (CPT-SSM). SSM composed of polyethylene glycol (PEGylated) phospholipids are attractive nanocarriers for CPT delivery because they are sufficiently small to extravasate through the leaky microvasculature of tumor and inflamed tissues for passive targeting. The purpose of this study was to develop a novel method of preparing CPT-SSM based on its pH dependent, reversible carboxylate-lactone conversion chemistry. CPT carboxylate was added to SSM at pH 5 that favored the formation of active but hydrophobic CPT lactone for spontaneous association with SSM. The kinetics of CPT conversion and CPT-SSM formation, and the effect of varying CPT-PEGylated phospholipid molar ratio on CPT-SSM properties and CPT solubilization were evaluated. CPT converted gradually from the carboxylate form to lactone, and CPT-SSM were formed after 12 h incubation. The mean size of CPT-SSM was ∼14 nm. CPT solubilization (∼12 μg/ml) and other CPT-SSM micelle properties did not change significantly with increasing CPT to PEGylated phospholipid molar ratios using this novel method, unlike the coprecipitation/reconstitution technique previously reported. This reproducible CPT solubilization in SSM was attributed to avoidance of drug aggregate formation by this method. The advantages of our solvent pH change method to prepare CPT-SSM support further investigations of this approach to other hydrophobic drugs similar to CPT in chemistry and also CPT molecular solubilization in other nanocarriers.