A quality by design approach for the synthesis of palmitoyl-L-carnitine-loaded nanoemulsions as drug delivery systems

Abstract

Nanoemulsions (NE) are lipid nanocarriers that can efficiently load hydrophobic active compounds, like palmitoyl-L-carnitine (pC), used here as model molecule. The use of design of experiments (DoE) approach is a useful tool to develop NEs with optimized properties, requiring less experiments compared to trial-and-error approach. In this work, NE were prepared by the solvent injection technique and DoE using a two-level fractional factorial design (FFD) as model was implemented for designing pC-loaded NE. NEs were fully characterized by a combination of techniques, studying its stability, scalability, pC entrapment and loading capacity and biodistribution, which was studied ex-vivo after injection of fluorescent NEs in mice. We selected the optimal composition for NE, named pC-NE U , after analysis of four variables using DoE. pC-NE U incorporated pC in a very efficient manner, with high entrapment efficiency (EE) and loading capacity. pC-NE U did not change its initial colloidal properties stored at 4 °C in water during 120 days, nor in buffers with different pH values (5.3 and 7.4) during 30 days. Moreover, the scalability process did not affect NE properties and stability profile. Finally, biodistribution study showed that pC-NE U formulation was predominantly concentrated in the liver, with minimal accumulation in spleen, stomach, and kidneys.

Assessing the In Vitro and In Vivo Performance of L-Carnitine-Loaded Nanoparticles in Combating Obesity

“…This suggests that long-chain acylcarnitine-specifically, palmitoyl-L-carnitine-may positively influence erythropoiesis [21]. Palmitoyl-L-carnitine has been used as a hydrophobic drug in the study by Arroyo-Urea, which was similar to our study [22].…”

“…They prepared the NEs using the solvent injection method and employed a fractional factorial design model to optimize the LC-loaded NEs. They efficiently incorporated LC with a high encapsulation efficiency (>90%) and loading capacity [22]. EE(Y 4 ) = +108.04 + 28.97X 1 + 14.53X 2 + 10.04X 3 (4) After evaluation of the results, NLC3 was selected as the optimum formulation.…”

Multimodal evaluation of drug antibacterial activity reveals cinnamaldehyde analog anti-biofilm effects against Haemophilus influenzae

“…Nanoemulsions (NE), lipid nanoparticles constituted by oil, water, and surfactants, were used for cinnamaldehyde analog encapsulation. The synthesis of (±)-α-tocopherol NE was previously described [ 41 ]. Briefly, an ethanolic organic phase containing (±)-α-tocopherol (Merck, 10191410), octadecylamine (Merck, 124301) and Tween 80 (Croda, SD82825) was rapidly injected into ultrapure water at room temperature (RT) under continuous stirring (700 r.p.m.).…”