Abstract
The evaluation of encapsulation efficiency is a regulatory requirement for the characterization of drug delivery systems. However, the difficulties in efficiently separating nanomedicines from the free drug may compromise the achievement of accurate determinations. Herein, ultrafiltration was exploited as a separative strategy towards the evaluation of methotrexate (MTX) encapsulation efficiency in nanostructured lipid carriers and polymeric nanoparticles. The effect of experimental conditions such as pH and the amount of surfactant present in the ultrafiltration media was addressed aiming at the selection of suitable conditions for the effective purification of nanocarriers. MTX-loaded nanoparticles were then submitted to ultrafiltration and the portions remaining in the upper compartment of the filtering device and in the ultrafiltrate were collected and analyzed by HPLC-UV using a reversed-phase (C18) monolithic column. A short centrifugation time (5 min) was suitable for establishing the amount of encapsulated MTX in nanostructured lipid carriers, based on the assumption that the free MTX concentration was the same in the upper compartment and in the ultrafiltrate. The defined conditions allowed the efficient separation of nanocarriers from the free drug, with recoveries of >85% even when nanoparticles were present in cell culture media and in pig skin surrogate from permeation assays.
Highlights
The promise held by nanomedicine of revolutionizing therapeutic outcomes has led to the extensive development of nanotechnology-based drug delivery systems [1,2,3]
The presence of 20% (v/v) acetonitrile (ACN, organic modifier in HPLC analysis) caused an increase in nanostructured lipid carriers (NLCs) size to ca. 505 nm, with no decrease in the intensity of scattering signal measured by dynamic light scattering
MTX was performed through the establishment of suitable ultrafiltration conditions for the separation of lipid and polymeric nanoparticles from free MTX
Summary
The promise held by nanomedicine of revolutionizing therapeutic outcomes has led to the extensive development of nanotechnology-based drug delivery systems [1,2,3]. These materials with dimensions in the nanometer range present unique properties and have been exploited as vehicles for the targeted delivery of pharmaceutical drugs, especially those with hampered therapeutic use [3,4,5]. Several methods have been employed for the separation of nanoparticles from the free drug, including size-exclusion chromatography, solid-phase extraction, X-ray small angle scattering (SAXS), ultrafiltration, ultracentrifugation, and dialysis [10,11,12,13,14]. The long time required for equilibration between the compartments defined by the dialysis membrane [12,15], and the poor separation of nanoparticles from free drug even at a high centrifugation speed [9,12,15]
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