Albumin‐Assisted Method Allows Assessment of Release of Hydrophobic Drugs From Nanocarriers

Abstract

Polymeric nanoparticles have been extensively studied as drug delivery vehicles both in vitro and in vivo for the last two decades. In vitro methods to assess drug release profiles usually utilize degradation of nanoparticles in aqueous medium, followed by the measurement of the concentration of the released drug. This method, however, is difficult to use for drugs that are poorly water soluble. In this study, a protocol for measuring drug release kinetic using albumin solution as the medium is described. Albumin is a major blood transport protein, which mediates transport of many lipid soluble compounds including fatty acids, hormones, and bilirubin. The use of a dialysis-based system utilizing albumin dialysate solution allows hydrophobic drug release from a diverse set of drug delivery modalities is demonstrated. The method using liposomes and PLGA nanoparticles as drug carriers, and two model hydrophobic drugs, 17β-estradiol, and dexamethasone is validated.

Focused ultrasound blood brain barrier opening mediated delivery of MRI-visible albumin nanoclusters to the rat brain for localized drug delivery with temporal control

“…This supports 290 previous studies highlighting either no inflammatory response or a brief transient 291 inflammatory response following BBB opening [37,38]. In addition, the use of 292 albumin-based drug carriers have previously been shown to be safe to administer IV 293 [21,[39][40][41][42][43][44] [21], and our work showed no clear additional inflammatory response or 294 cellular toxicity with the presence of albumin NCs in the brain [42,45]. The presence of 295 NCs in brain regions that were not targeted for BBB opening was also not observed.…”

“…42 The NCs are MRI visible and provide independent confirmation of the site of drug 43 delivery. NCs are also stable in circulation, and once delivered to target brain regions, 44 we were able to induce drug and dye release by a second FUS treatment. The release of 45 glutamate from NCs in vivo caused local neuronal activation demonstrating that the 46 drug loading capacity of the NCs is sufficient for inducing localized changes in neural 47 activity with temporal control.…”

Transfer of Lipophilic Drugs from Nanoemulsions into Lipid-Containing Alginate Microspheres

“…Correlation to in vivo conditions is thus unreasonable since the physiological situation is not reflected properly. To enhance solubility in a closer to physiological way, the release medium can, for example, be supplemented with albumin [5,14]. With regard to intravenous administration, there are many lipophilic binding or distribution sites such as (lipo)proteins or cell compartments in the blood.…”

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“…The IVR study was performed by the dialysis bag diffusion method using a dialysis membrane (MWCO 12000 to 14000, Himedia) 13,14 . The membrane was soaked in water at room temperature for overnight before use.…”