Development of membrane by electrospinning containing semi-synthetic derivatives of Artemisia annua Linnaeus

Chinese scientists isolated artemisinin from Artemisia annua that provided effective protection against multi-drug resistant strains of P. falciparum. This compound is both insoluble in water and oil, and therefore derivatives with better physicochemical properties were produced by semi-synthesis, including artemether that is currently a first -line drugs for malaria treatment [1,3]. Malaria is among neglected diseases, which kill approximately 300 million people per year worldwide [2,3]. Scientists are continuously in search for new formulations with stability and greater patient's adherence to treatment. Here we report the development of pharmaceutical systems with controlled drug release. Methods: Membrane preparations containing B) 2,5% and C) 5% artemether were produced with 13,6% A) poli(ε-caprolactone) (PCL) solution dissolved in a 1:1 acetone:chloroform mixture by weight and maintained under mechanical agitation for 1 hour. For the electrospinning process, a system comprising of an infusion pump, and a high voltage power source was employed under the experimental conditions: with DC input of 14 kV, flow rate 8mL/h; working distance 17 cm; needle 21Gx1" connected to the positive pole; electrospinning duration: 20 minutes (duplicate for each solution). The fibers were deposited on a metal collector plane, connected to the negative pole, coated with aluminum foil. The fibers' morphology and diameter was analyzed by Scanning Electron Microscope (SEM). The fibers' diameters were measured using ImageJ® software. Results: According to the results, the membranes with PCL/drug containing the active pharmaceutical ingredient presented large area uniformity, mechanical flexibility and strong adhesion to substrates. From SEM analysis (Figure 1), furthermore, as expected, fibers with higher drug concentration presented higher average diameters of 2,28 ± 1,05 µm and 1,10 ± 0,75 µm for 5 and 2,5wt% drug, respectively. Conclusions: This membrane is promising candidate for development of new solid or semi-solid formulations for topical application or transdermal antimalarial product in a single dose.

A) PCL

B) 2,5% Artemether

C) 5% Artemether Fig. 1: Micrographic images of A) PCL fibers and B) and C) PCL/drug obtained by electrospinning.

Acknowledgements: FAPESP project n° 2014/16008 – 3, CNPq, CAPES.

Keywords: Electrospinning, artemether, malaria, poli (ε-caprolactone).

References:

[1] Who, World Health Organization. Malaria. 2014; 94, March.

[2] Who, World Health Organization. Guidelines for the treatment of Malaria. 2015; 3 rd ed.

[3] Visser BJ, Wieten RW, Kroon D, Nagel IM, Bélard S, Van Vugt M, Grobusch MP. Efficacy and safety of artemisinin combination therapy (ACT) for non-falciparum malaria: a systematic review. Malar J 2014; 13: 463.

No conflict of interest has been declared by the author(s).