Pralidoxime is an organophosphate antidote with poor central nervous system distribution due to a high polarity. In the present study, pralidoxime-loaded poly(lactic-co-glycolic acid) nanoparticles were prepared and evaluated as a potential delivery system of the drug into the central nervous system. The nanoparticles were prepared using double emulsion solvent evaporation method. Poly(lactic-co-glycolic acid) (PLGA) in ethyl acetate made the organic phase and pralidoxime in water made the aqueous phase. The system was stabilized by polyvinyl alcohol. Different drug/polymer ratios were used (1 : 1, 1 : 2, and 1 : 4) and the fabricated particles were characterized for encapsulation efficiency using UV-VIS Spectroscopy; particle size distribution, polydispersity index, and zeta potential using photon correlation spectroscopy; and in vitro drug release profile using UV-VIS Spectroscopy. Mean particle sizes were 386.6 nm, 304.7 nm, and 322.8 nm, encapsulation efficiency was 28.58%, 51.91%, and 68.78%, and zeta potential was 5.04 mV, 3.31 mV, and 5.98 mV for particles with drug/polymer ratios 1 : 1, 1 : 2, and 1 : 4, respectively. In vitro drug release profile changed from biphasic to monobasic as the drug/polymer ratio decreased from 1 : 1 to 1 : 4. Stable pralidoxime-loaded PLGA nanoparticles were produced using double emulsion solvent evaporation techniques.

Crinum macowanii has been found to contain alkaloids that have activity against acetylcholinesterase enzyme in vitro. The present study was undertaken to investigate the in vivo ability of hydroethanolic crude extract of Crinum macowanii to ameliorate memory impairment induced by scopolamine. Thirty-six male Balb/c mice weighing around 25–35 g were employed in the present investigation. Y-maze and novel object recognition apparatus served as the exteroceptive behavioural models, and scopolamine-induced amnesia served as the interoceptive behavioural model. C. macowanii (10, 20, and 40 mg/kg p.o.) was administered in single doses to the mice. Donepezil (3 mg/kg p.o.) was used as a positive control agent. C. macowanii extract reversed the amnesia induced by scopolamine as indicated by a dose-dependent increase in spontaneous alternation performance in the Y-maze task. C. macowanii 40 mg/kg showed significant activity (p < 0.05 versus negative control), comparable to that of the positive control. C. macowanii also showed memory-enhancing activity against scopolamine-induced memory deficits in the long-term memory novel object recognition performance as indicated by a dose-dependent increase in the discrimination index. The results indicate that the hydroethanolic extract of C. macowanii may be a useful memory restorative mediator in the treatment of cognitive disorders such as Alzheimer's disease.

Background Artesunate is one of the most potent, rapidly acting and therapeutically versatile antimalarial drugs. Its efficacy is hampered by poor aqueous solubility and stability resulting in low oral bioavailability. Recent efforts to nanoformulate artesunate have shown great potential of improving its dissolution profile and bioavailability. However, no study has yet been done to investigate the intestinal permeability of these nanoformulations, which is a critical determinant of systemic absorption. Objective of the Study The main aim of the study was to determine the intestinal permeability of artesunate-loaded solid lipid nanoparticles (SLN). Method The microemulsion dilution technique was used to fabricate artesunate-loaded solid lipid nanoparticles. In vitro drug release studies were performed at pH 1.2 and 6.8 using the dialysis membrane method. The everted gut sac method was used to assess the intestinal permeability of the prepared nanoparticles. Results The average particle size was 1109 nm and the polydispersity index (PDI) was 0.082. The zeta potential was found to be −20.7 mV. The encapsulation efficiency of the solid lipid nanoparticles obtained was 51.7%. At both pH 1.2 and 6.8, pure artesunate was rapidly released within the first 30 mins while the SLN showed a biphasic release pattern with an initial burst release during the first hour followed by a prolonged release over time. The rate of drug release increased with increasing pH. The apparent permeability (Papp) of SLN was found to be greater (0.169 mg/cm2) as compared to that of pure artesunate (0.117 mg/cm2) at the end of the experiment. Conclusion The results obtained in this study showed that the microemulsion dilution technique can be used to formulate artesunate solid lipid nanoparticles. The formulation exhibited a sustained drug release profile. The intestinal permeability of artesunate could be enhanced by the nanoformulation.

Crinum macowanii is a bulbous plant indigenous to many parts of Southern Africa. Extracts of C. macowanii have gained interest since the discovery of various alkaloids, few of which possess acetylcholinesterase inhibitory activity. The present study was performed to evaluate the effect of a crude hydroethanolic extract of C. macowanii against aluminum chloride-induced memory impairment in mice using the Morris water maze and the novel object recognition task. C. macowanii (10, 20, and 40 mg/kg p.o) was administered daily for five weeks, while donepezil (3 mg/kg p.o) was used as the positive control. C. macowanii at a dosage of 40 mg/kg showed a significantly lower escape latency than the negative control (P < 0.0001) and was found to be comparable to donepezil 3 mg/kg in the Morris water maze test. C. macowanii at 40 mg/kg exhibited a significantly higher discrimination index than aluminum chloride-treated mice in the novel object recognition task. The results may support the usefulness of C. macowanii in the management of dementia and related illnesses.

Boophone disticha (B. disticha) has been used systemically in traditional medical practice in Zimbabwe and neighbouring countries for the management of various central nervous system conditions including hysteria. Abuse of the plant by teenagers in Zimbabwe for its claimed hallucinogenic effects has also been reported, with the advent of serious toxicity in some cases. In the present work, we describe the acute toxicity and neurotoxicological effects of a freeze dried hydro-ethanolic plant extract of the bulb of B. disticha. Thirty-three adult (6—12 weeks old), non-pregnant female Sprague Dawley rats were used for the oral LD50 estimation. Animals were given doses of 50, 120, 240, 360, 500 and 700 mg/kg and were observed using a modified Functional Observation Battery (FOB) for behavioural toxicity. The estimated oral LD50 of the plant extract was between 120 and 240 mg/kg. For doses of 240 mg/kg and less, signs of toxicity began approximately 10 minutes after gavage, and the most prominent initial signs were head tremors (at 50 mg/kg) and body tremors, severe body tremors(>360 mg/kg) followed by convulsions. Generally, symptoms of toxicity lasted approximately 2 hours for doses of 240 mg/kg and less; and 3 hours for doses over 240 mg/kg for animals that survived. These results point to a rapid gastrointestinal absorption of the active principles in the plant extract. The most prominent neurotoxicological effects were increased flaccid limb paralysis and spastic hind-limb paralysis. Tachypnoea was noted at low doses and higher doses produced laboured breathing. The retropulsion observed with higher doses could indicate the reported hallucinogenic effects of the plant extract.

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We conclude that cyproheptadine has a dose-dependent protective effect on mortality and toxicity produced by exposure to Boophone disticha in our mouse model of toxicity.