Preformulation Study of Electrospun Haemanthamine-Loaded Amphiphilic Nanofibers Intended for a Solid Template for Self-Assembled Liposomes

Abstract

Haemanthamine (HAE) has been proven as a potential anticancer agent. However, the therapeutic use of this plant-origin alkaloid to date is limited due to the chemical instability and poorly water-soluble characteristics of the agent. To overcome these challenges, we developed novel amphiphilic electrospun nanofibers (NFs) loaded with HAE, phosphatidylcholine (PC) and polyvinylpyrrolidone (PVP), and intended for a stabilizing platform (template) of self-assembled liposomes of the active agent. The NFs were fabricated with a solvent-based electrospinning method. The chemical structure of HAE and the geometric properties, molecular interactions and physical solid-state properties of the NFs were investigated using nuclear magnetic resonance (NMR) spectroscopy, scanning electron microscopy (SEM), photon correlation spectroscopy (PCS), Fourier transform infrared (FTIR) spectroscopy, X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC), respectively. An in-house dialysis-based dissolution method was used to investigate the drug release in vitro. The HAE-loaded fibers showed a nanoscale size ranging from 197 nm to 534 nm. The liposomes with a diameter between 63 nm and 401 nm were spontaneously formed as the NFs were exposed to water. HAE dispersed inside liposomes showed a tri-modal dissolution behavior. In conclusion, the present amphiphilic NFs loaded with HAE are an alternative approach for the formulation of a liposomal drug delivery system and stabilization of the liposomes of the present alkaloid.

Solid State Stability and Kinetics of Degradation for Candesartan—Pure Compound and Pharmaceutical Formulation

“…The thermal behavior of active pharmaceutical ingredients (APIs) as pure components in binary mixtures with excipients and in pharmaceutical formulations is of great importance in drug science [21][22][23][24][25][26]. Even if in the case of pharmaceuticals, the term "stability" is usually correlated with the loss of the active pharmaceutical ingredient from formulation, and "solid-state stability" can also designate the response of an API or a pharmaceutical formulation to thermal stress.…”

Flavonoids and alkaloids from the rhizomes of Zephyranthes ajax Hort. and their cytotoxicity

“…Compound 8 has been proven to have a cytotoxic activity, but it is very poorly soluble in water. Therefore, we recently developed novel haemanthamine (compound 8)-loaded amphiphilic nanofibers to overcome these formulation challenges 26 . Noticeably, secondary metabolites from natural products have been the most successful leads in the discovery and development of www.nature.com/scientificreports/ novel drugs 27,28 .…”

“…Hence, the development of novel drug delivery systems for natural compounds could resolve these critical issues, thus leading to novel and versatile applications of natural products in medicine. In our recent study, we succeeded to yield (through extraction and crystallization) haemanthamine (compound 8) in the amounts enough to fabricate the active-loaded amphiphilic nanofibers 26 . The results suggested that the formulation of such amphiphilic nanofibers for haemanthamine could provide a promising drug delivery system for the present large-molecule and poorly water-soluble active agent.…”

Scale-up of Electrospinning: Market Overview of Products and Devices for Pharmaceutical and Biomedical Purposes

“…Ideal drug delivery systems have been developed to achieve the best therapeutic effects and lowest toxicity problems [ 1 ]. The rapid progress in the field of nanotechnology has led to the development of many techniques for the production of numerous nano-scale composites [ 2 , 3 ], of which nanofibers have received considerable attention [ 4 ] due to diversity in the fabrication technologies and applications [ 5 , 6 ], especially in the fields of pharmaceutical drug delivery [ 7 , 8 , 9 ], biomedical applications including wound dressing [ 10 , 11 , 12 , 13 ], and tissue engineering [ 14 , 15 ]. Electrospinning (ES) has been considered one of the most efficient techniques used for the synthesis of nanomaterials since the 20th century [ 16 ], and great works have been done in the late 1990s and early part of the 21st century [ 17 , 18 ].…”