Abstract
Low aqueous solubility and poor oral bioavailability are limiting factors in the oral delivery of voxelotor, an antisickling agent. To overcome these limitations, a voxelotor self-nanoemulsifying drug delivery system was developed. Various oils, surfactants, and cosurfactants were screened for their solubilization potential for the drug. The area of nanoemulsification was identified using a ternary phase diagram. An experimental mixture design and a desirability function were applied to select SNEDDSs that contain a maximum amount of lipids and a minimum amount of surfactant, and that possess optimal emulsification properties (i.e., droplet sizes, polydispersity index (PDI), emulsification time, and transmittance percentage). The optimized SNEDDS formulation was evaluated for the self-emulsifying time (32 s), droplet size (35 nm), and zeta potential (−8 mV). In vitro dissolution studies indicated a 3.1-fold improvement in drug solubility from the optimized SNEDDS over pure drug powder. After 60 min of in vitro lipolysis, 88% of the voxelotor loaded in the SNEDDS remained in the aqueous phase. Cytotoxicity evaluation, using Caco-2 cells, indicated the safety of the formulation at 0.9 mg/mL. The transport of the voxelotor SNEDDS across Caco-2 monolayers was significantly enhanced compared to that of the free drug. Compared to the drug suspension, the developed SNEDDS enhanced the oral bioavailability (1.7-fold) of voxelotor in rats. The results suggest that further development of SNEDDSs for the oral delivery of voxelotor is needed.
Highlights
During recent decades, the number of sickle cell disease (SCD) patients has increased significantly, making it the most common genetic disorder affecting millions of people worldwide, in sub-Saharan Africa [1]
An experimental mixture design and a desirability function were applied to select self-nanoemulsifying drug delivery systems (SNEDDSs) that contain a maximum amount of lipids and a minimum amount of surfactant, and that possess optimal emulsification properties (i.e., droplet sizes, polydispersity index (PDI), emulsification time, and transmittance percentage)
Capryol PGMC® was selected as the oily phase for further studies
Summary
The number of sickle cell disease (SCD) patients has increased significantly, making it the most common genetic disorder affecting millions of people worldwide, in sub-Saharan Africa [1]. The cellular sickling process can be reduced by increasing the oxygen affinity of haemoglobin S (HbS). The literature has reported that increasing the concentration of oxygenated HbS, without compromising oxygen delivery, is a promising approach to prevent red blood cell sickling and, subsequently, achieve long-term disease improvement [3]. Voxelotor (Vox), known as GBT-440, is a small compound that binds to HbS and increases its affinity for oxygen. Vox improves the in vitro red blood cell flexibility and Pharmaceutics 2021, 13, 1388.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
