Pharmacogenomics Dictate Pharmacokinetics: Polymorphisms in Drug-Metabolizing Enzymes and Drug-Transporters

Mondal, Debasis; Gerlach, Samantha L.; Datta, Amrita; Chakravarty, Geetika; Abdel‐Mageed, Asim B.

doi:10.5772/33792

Cited by 1 publication

(2 citation statements)

References 211 publications

(211 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, bicelles, which are flat lipid bilayers that mimic a minimum unit of cell membranes 26 are expected to enable passive drug loading into bicelles through simple diffusion, similar to drug penetration in cells. 27 This study aimed to confirm our concept using a passive loading method, as shown in Figure 1 . The passive loading can be conducted with a small amount of a drug substance, minimum resources, and simple and inexpensive equipment.…”

Section: Introductionmentioning

confidence: 90%

“…Remote loading, a technique used to load drugs into the inner aqueous phase of liposomes, is a well-known method for efficient drug encapsulation. , In contrast, it cannot be applied to bicelles because they lack an inner water phase, which is the driving force for remote loading based on the pH gradient and ammonium sulfate gradient between the inner and outer water phases. However, bicelles, which are flat lipid bilayers that mimic a minimum unit of cell membranes are expected to enable passive drug loading into bicelles through simple diffusion, similar to drug penetration in cells . This study aimed to confirm our concept using a passive loading method, as shown in Figure .…”

Section: Introductionmentioning

confidence: 91%

See 1 more Smart Citation

Efficient Drug Loading Method for Poorly Water-Soluble Drug into Bicelles through Passive Diffusion

Arai,

Iwao,

Muguruma

et al. 2023

Mol. Pharmaceutics

View full text Add to dashboard Cite

The bicelle, a type of solid lipid nanoparticle, comprises phospholipids with varying alkyl chain lengths and possesses the ability to solubilize poorly water-soluble drugs. Bicelle preparation is complicated and time-consuming because conventional drug-loading methods in bicelles require multiple rounds of thermal cycling or co-grinding with drugs and lipids. In this study, we proposed a simple drug-loading method for bicelles that utilizes passive diffusion. Drug-unloaded bicelles were placed inside a dialysis device and incubated in a saturated solution of ketoconazole (KTZ), which is a model drug. KTZ was successfully loaded into bare bicelles over time with morphological changes, and the final encapsulated concentration was dependent on the lipid concentration of the bicelles. When polyethylene glycol (PEG) chains of two different lengths (PEG2K and 5K) were incorporated into bicelles, PEG2k and PEG5k bicelles mitigated the morphological changes and improved the encapsulation rate. This mitigation of morphological changes enhanced the encapsulated drug concentration. Specifically, PEG5k bicelles, which exhibited the greatest prevention of morphological changes, had a lower encapsulated concentration after 24 h than that of PEG2k bicelles, indicating that PEGylation with a longer PEG chain length improved the loading capacity but decreased the encapsulation rate owing to the presence of a hydration layer of PEG. Thus, PEG with a certain length is more suitable for passive loading. Moreover, loading factors, such as temperature and vehicles used in the encapsulation process, affected the encapsulation rate of the drug. Taken together, the passive loading method offers high throughput with minimal resources, making it a potentially valuable approach during early drug development phases.

show abstract

Section: Introductionmentioning

confidence: 90%