Malaria is a public health problem in more than 90 countries, inhabited by a total of some 2.4 billion people or about 40% of the world’s population [
1,
2]. Mortality due to malaria stood at 429,000 deaths worldwide in 2015, with 90% of these occurring in sub-Saharan Africa and the majority being children under 5 years of age [
2]. In Kenya, malaria is the leading cause of morbidity and mortality where more than 70% of the population live in malaria risk areas and accounting for nearly 15% of all out-patient attendance in the health facilities admissions and 10% of hospital admissions [
3‐
5]. The high morbidity and mortality in sub-Saharan Africa are due to
Plasmodium falciparum, the most virulent of the five malarial parasites that infect humans. Successful malaria elimination is still a challenge in the absence of new vaccines, drugs and vector control strategies. This challenge, more especially in terms of chemotherapy and vaccine development, is attributed to the complex life cycle of the parasite where it is able to hide, propagate itself and transfer itself between hosts [
6]. In the absence of an effective vaccine, chemotherapy is the only option readily available for managing malaria. Much of this morbidity and mortality could be avoided if drugs available to patients were efficacious, of high quality and used correctly [
7]. Chloroquine (CQ) was, for several decades, the anti-malarial drug of choice due to its safety, high efficacy and low cost [
8]. However, due to the widespread prevalence of chloroquine-resistant (CQR) parasite strains, CQ was replaced as the front-line anti-malarial chemotherapy in the late 1990s. Artemisinins are the most potent compounds in the anti-malarial drug arsenal and no suitable replacements are expected any time soon [
7]; artemisinin-based combination therapy (ACT) is currently the recommended first-line treatment of uncomplicated falciparum malaria [
9]. A report of resistance to ACT in South East Asia has further complicated malaria control efforts [
10]. Increased efforts in anti-malarial drug discovery are, therefore, urgently needed but, in the absence of new drugs, drug reformulation, more specifically drug delivery, seems an attractive option [
11,
12]. One possible strategy is to reformulate the available anti-malarials in an innovative way and nanotechnology has emerged as the best way of delivering the drugs to target site while potentially mitigating resistance [
13,
14].
Targeted drug delivery systems can provide an increased drug bioavailability and selectivity in achieving the intake of total amounts of drugs sufficiently low to not be harmful to patients but high enough to kill the parasite. Recent studies by Fernandez-Busquets and co-workers demonstrated that heparin-functionalized liposomal nanocarriers can selectively deliver the drug cargo to parasitized red blood cells (pRBCs) over non-infected ones (uRBCs) [
15‐
18]. Incorporation of heparin to nanoparticles showed improved stealth capable of bypassing clearance by the reticuloendothelial system, improved targeting of molecules with enhances uptake and accumulation and increased stability and solubility [
19]. Furthermore, over and above targeting, heparin also provides a dual action to the drugs because of its inherent anti-malarial activity [
18]. Notwithstanding the fact that liposomes have an advantage of mimicking biological systems, their use has been associated with various shortcomings such as poor stability, “leakage” and delivering very small quantities of drugs in the target site to have any noticeable biological effect [
20,
21]. Thus, the current study proposes to reformulate CQ in more robust heparin-surfaced functionalized solid-lipid nanoparticles (SLNs) and evaluate the in vitro against chloroquine sensitive and chloroquine resistant
P. falciparum strains.