This chapter X-rayed antimalarial drug resistance (ADR) by plasmodium species with a particular focus on P. falciparum, which is the most deadly species of the malaria parasite responsible for over 90% of the global malaria burden domiciled in Sub-Saharan Africa. The introduction intently looked at malaria therapeutics across the decades and the development of drug resistance by the parasite. With the malaria parasite (P. falciparum) as the focal point, the mechanisms by which they develop resistance to antimalarial drugs was looked at, including factors affecting drug resistance development. Armed with this knowledge, the chapter also highlighted the therapeutic interventions taken against this hydra-headed monster together with their limitations and recent advances towards addressing those limitations or opening new frontiers for research exploration. Future perspectives that will provide research strategy and direction as possible tools for combating drug resistance development by the malaria parasite were also discussed.

Aim: Anterior eye segment disorders are treated with eye drops and ointments, which have low ocular bioavailability necessitating the need for improved alternatives. Lipid microsuspension of gentamicin sulphate was developed for the treatment of susceptible eye diseases. Materials & methods: Lipid microsuspensions encapsulating gentamicin sulphate were produced by hot homogenization and evaluated. Ex vivo permeation and ocular irritancy tests were also conducted. Results & conclusion: Stable microsuspensions with high entrapment efficiency and satisfactory osmolarities were obtained. Release studies achieved 49–88% in vitro release at 12 h with sustained permeability of gentamicin compared with conventional gentamicin eye drop (Evril®). No irritation was observed following Draize’s test. The microsuspensions have great potential as ocular delivery system of gentamicin sulphate.

Quinine (QHCl) as an antimalarial drug has remained very relevant 400 years after its effectiveness was discovered. Unlike other antimalarials, the development of resistance to quinine has been slow. Hence, this drug is till date still used for the treatment of severe and cerebral malaria, for malaria treatment in all trimesters of pregnancy, and in combination with doxycycline against multi-drug resistant parasites. The declined in its administration over the years is mainly associated with poor tolerability due to its gastrointestinal (GIT) side effects such as cinchonism, complex dosing regimen and bitter taste, all of which result in poor compliance. Hence our research was aimed at redesigning quinine using nanotechnology and investigating an alternative route for its administration for the treatment of malaria. A nanosuspension (NS) of QHCl was formulated to suit intranasal administration. QHCl-NS was prepared using lipid matrices made up of solidified reverse micellar solutions (SRMS) comprising Phospholipon® 90H and lipids (Softisan® 154 or Compritol®) in 1:2 ratio, while Poloxamer® 188 (P188) and Tween® 80 (T80) were used as stabilizer and surfactant. The QHCl-NS formulated were in nanosize range (68.6±0.86 to 300.8±10.11 nm), and highly stable during storage. QHCl-NS achieved above 80 % in vitro drug release in 6 h. Ex vivo permeation studies revealed that formulating QHCl as NS resulted in a 5-fold and 56- fold increase in flux and permeation coefficient, respectively, thereby enhancing permeation through pig nasal mucosa better than plain drug solutions. This implies that the rate of absorption as well as ease of drug permeation through porcine nasal mucosa was impressively enhanced by formulating QHCl as NS. Most importantly, reduction in parasitaemia in mice infected with plasmodium berghei ANKA by QHCl-NS administered through the intranasal route (51.16 %) was comparable to oral administration (52.12 %). Therefore, redesigning QHCl as NS for intranasal administration has great potentials to serve as a more tolerable options for the treatment of malaria in endemic areas.

Quinine hydrochloride (QHCl) has remained a very relevant antimalarial drug 400 years after its effectiveness was discovered. Unlike other antimalarials, the development of resistance to quinine has been slow. Hence, this drug is to date still used for the treatment of severe and cerebral malaria, for malaria treatment in all trimesters of pregnancy, and in combination with doxycycline against multidrug-resistant malaria parasites. The decline in its administration over the years is mainly associated with poor tolerability due to its gastrointestinal (GIT) side effects such as cinchonism, complex dosing regimen and bitter taste, all of which result in poor compliance. Hence, our research was aimed at redesigning quinine using nanotechnology and investigating an alternative route for its administration for the treatment of malaria. QHCl nanosuspension (QHCl-NS) for intranasal administration was prepared using lipid matrices made up of solidified reverse micellar solutions (SRMS) comprising Phospholipon® 90H and lipids (Softisan® 154 or Compritol®) in a 1:2 ratio, while Poloxamer® 188 (P188) and Tween® 80 (T80) were used as a stabilizer and a surfactant, respectively. The QHCl-NS formulated were in the nanosize range (68.60 ± 0.86 to 300.80 ± 10.11 nm), and highly stable during storage, though zeta potential was low (≤6.95 ± 0.416). QHCl-NS achieved above 80% in vitro drug release in 6 h. Ex vivo permeation studies revealed that formulating QHCl as NS resulted in a 5-fold and 56-fold increase in the flux and permeation coefficient, respectively, thereby enhancing permeation through pig nasal mucosa better than plain drug solutions. This implies that the rate of absorption as well as ease of drug permeation through porcine nasal mucosa was impressively enhanced by formulating QHCl as NS. Most importantly, reduction in parasitaemia in mice infected with Plasmodium berghei ANKA by QHCl-NS administered through the intranasal route (51.16%) was comparable to oral administration (52.12%). Therefore, redesigning QHCl as NS for intranasal administration has great potential to serve as a more tolerable option for the treatment of malaria in endemic areas.

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