Abstract
Artemisinins, the mainstay in the treatment of malaria today, are used in combination with other antimalarials to forestall resistance, as artemisinin-combination therapies. In line with the World Health Organization’s recommendation in that respect, solid lipid nanoparticles (SLN) were formulated to encapsulate two antimalarial drugs — artemether and lumefantrine. The nanoparticles were evaluated for size and solid state properties. Caco-2 cells were used to investigate the ability of the SLN to deliver its payload at the absorptive interface of the gastrointestinal tract. Mice heart endothelial cells (MHEC) were also used as marker cells to assess cellular uptake of coumarin 6 from the SLN with imaging by confocal laser scanning microscopy (CSLM). In vivo antimalarial activity was done using a standard suppressive protocol. The results of this study revealed different crystal properties for artemether and lumefantrine, which affected their solubility in the lipid matrix and thus, loading in the lipid nanoparticles. The particles of the SLN were within the range of 150 nm–500 nm with varied polydispersity indices. Wide angle X-ray diffraction analysis indicated the presence of particles of solid nature. Cellular uptake studies indicated uptake of coumarin 6 from the coumarin 6-labeled SLN. In vivo antimalarial studies indicated high clearance of parasitemia with minimal effect on hematological parameters tested.
About the authors
Anthony A. Attama is a Professor of Pharmaceutics at the University of Nigeria, Nsukka, where he studied Pharmacy and obtained his PhD in 2002. Prof. Attama was at the Institut für Pharmazeutische Technologie, Technische Universität Braunschweig, Germany for his postdoctoral research in Pharmaceutical Nanotechnology. He is the leader of the Drug Delivery and Nanomedicines Research Group of the University of Nigeria, Nsukka. He supervises postgraduate students and has published widely in peer-reviewed high impact journals. Prof. Attama has won many honours and research grants and has also attended many conferences. He has fostered the establishment of some pharmaceutical industries in Nigeria.
Franklin C. Kenechukwu is a lecturer in the Department of Pharmaceutics, University of Nigeria, Nsukka (UNN). He is currently running his Doctor of Philosophy Degree (PhD) programme (specialty: Drug Delivery and Formulation). In addition, he has published several articles in areas of drug delivery and formulation in both national and international journals, has served as reviewer to reputable journals and has contributed several chapters in printed books as well as a chapter titled ‘Nanoemulsions — advances in formulation, characterization and applications in drug delivery’ in a published electronic book and also a chapter titled ‘Cellulose-based biopolymers: formulation and delivery applications’ in Encyclopedia of Biomedical Polymers and Polymeric Biomaterials, a Handbook of Encapsulation and Controlled Release, New York, USA. He is the Secretary of the Departmental Research Grants Committee.
Ebele B. Onuigbo is a senior lecturer in the Department of Pharmaceutics, University of Nigeria, Nsukka. She graduated with a B. Pharm in 2000 and Masters of Pharmacy degree in 2006. In 2007, she was employed as lecturer I and rose to senior lecturer (current position). She completed her PhD in 2011. Her academic interests are immunology and infectious diseases. She teaches undergraduate and postgraduate students and has supervised many undergraduate projects. She has published in local and international journals. She has attended many conferences in Nigeria and abroad. She has also won many travel awards and research grants.
Petra O. Nnamani is senior lecturer in the Department of Pharmaceutics, University of Nigeria, Nsukka (UNN). She obtained her B. Pharm in 2001 and her M. Pharm in 2004 both from UNN. During her PhD (2006–2010), Petra joined the nanotechnology group at ICS-UNIDO in Trieste, Italy in 2009 for early research training in nanotechnology. She obtained her PhD in Drug Delivery in 2010 from UNN. Petra has had postdoc positions in SUK, India and HIPS-Saarland, Germany. She has published widely as well as attended conferences. She is a recipient of Stars in Global Health Round Four Phase 1 Award (Ref. S4-0251-01) by the Grand Challenges Canada.
Christel C. Müller-Goymann holds a full-professorship at the Institut Pharmazeutische Technologie, Technische Universität Braunschweig, Germany since 1991. Her research focuses on the physicochemical characterization of colloidal systems for dermal, transdermal and mucosal administration including pulmonary and ocular application. The evaluation of the formulations with regard to tissue interaction, penetration and permeation is performed with isolated human tissue from tissue donations and with tissue-engineered 3D constructs.
Acknowledgments:
Prof. A. A. Attama wises to acknowledge the support of Alexander von Humboldt Stiftung (NRI 1112681 STP), Bonn-Bad Godesberg, Germany through a Return Fellowship Award. The various contributions of the laboratory staff of Institut für Pharmazeutische Technologie, Technische Universität Braunschweig and Department of Pharmaceutics, University of Nigeria, Nsukka are highly acknowledged.
Conflict of interest statement: Authors state no conflict of interest. All authors have read the journal’s publication ethics and publication malpractice statement available at the journal’s website and hereby confirm that they comply with all its parts applicable to the present scientific work.
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