Development of Amphotericin B-Loaded Cubosomes Through the SolEmuls Technology for Enhancing the Oral Bioavailability

Abstract

Abstract. The oral administration of amphotericin B (AmB) has the major drawback of poor bioavailability. The aim of this work was to evaluate the potential of AmB-loaded cubosomes as an oral formulation with improved bioavailability. This manuscript firstly developed AmB-loaded cubosomes by using the SolEmuls technology. The encapsulation efficiency, the in vitro release, and stability studies in simulated gastrointestinal fluid were used to evaluate AmB-loaded cubosomes. The acute nephrotoxicity, bioavailability, and tissue distribution study of AmB-loaded cubosomes were assayed upon oral administration to rats. SAXS and cryo-TEM exhibited AmB-loaded cubosomes as a bicontinuous cubic liquid crystalline phase with Pn3m geometry. The encapsulation efficiency and the results of in vitro release and stability studies in simulated gastrointestinal fluid further demonstrated that AmB was successfully encapsulated in cubosomes. AmB-loaded cubosomal formulation orally administrated in rats did not show nephrotoxicity and its relative bioavailability was approximately 285% as compared to Fungizone®. The AmB-loaded cubosomal formulation presented an effective potential approach for enhancing the oral bioavailability of AmB.

Cubic phase nanoparticles for sustained release of ibuprofen formulation characterization and enhanced bioavailability study

“…Similar results were also reported in previous literature. 17,23 In the current study, the initial burst release of ibuprofen from cubic nanoparticles was probably attributed to either the surface-bound moieties or an aqueous environment allowing increased water penetration. Afterwards, the cubic nanoparticles manifested the sustained release characteristics that appeared to be dependent on the hydrophobicity of ibuprofen incorporated in the cubic nanoparticles.…”

“…20,21 The abilities of cubic phases to incorporate drugs for controlled release and enhanced drug bioavailability make it an interesting drug delivery system for oral, topical (or mucosal), and intravenous administration, with extensive applications in a multitude of dosage forms. 18,[22][23][24][25][26] However, few studies have assessed the application of cubic phases in ibuprofen oral drug delivery. Therefore, the objective of this study was to develop a nanoparticulate delivery system by using PYT and F127, which could solubilize ibuprofen in aqueous media, reaching the clinically relevant concentration and delivering ibuprofen in a controlled manner.…”

Evaluating the potential of cubosomal nanoparticles for oral delivery of amphotericin B in treating fungal infection

“…6 Experiments were performed using YM-100 centrifugal tubes from Millipore Corporation (Billerica, MA, USA). After centrifuging the cubosome dispersion at 15,000 rpm for 30 minutes, the free AmB with filtrate was removed through the bottom of the reservoir of the centricon, with a certain pore size.…”

“…As expected, the AUC value for oral administration of AmB loaded in GMO cubosomes was higher than for administration of oral Fungizone ® , even equivalent to that of AmB loaded in PHY cubosomes. 6 The study also pointed out that the poor absorption of Fungizone ® could contribute to the aggregation state found in SGF, despite that Fungizone ® was made into a micellar system.…”

“…The dose of AmB-loaded cubosomes may play a key role in the kidney distribution, as reported in PHY cubosomes and emulsion. 6,35 A possible reason for the kidney distribution of AmB-loaded cubosomes need to be elucidated in future research. Furthermore, in view of unique, multilayer cubosomal structures and bicontinuous cubic phase in excess water, GMO cubosomes are more stable, in comparison to emulsion.…”