Boitumelo Semete

In vivo uptake and acute immune response to orally administered chitosan and PEG coated PLGA nanoparticles.

Nanoparticulate drug delivery systems offer great promise in addressing challenges of drug toxicity, poor bioavailability and non-specificity for a number of drugs. Much progress has been reported for nano drug delivery systems for intravenous administration, however very little is known about the effects of orally administered nanoparticles. Furthermore, the development of nanoparticulate systems necessitates a thorough understanding of the biological response post exposure. This study aimed to elucidate the in vivo uptake of chitosan and polyethylene glycol (PEG) coated Poly, DL, lactic-co-glycolic Acid (PLGA) nanoparticles and the immunological response within 24 h of oral and peritoneal administration. These PLGA nanoparticles were administered orally and peritoneally to female Balb/C mice, they were taken up by macrophages of the peritoneum. When these particles were fluorescently labelled, intracellular localisation was observed. The expression of pro-inflammatory cytokines IL-2, IL-6, IL-12p70 and TNF-α in plasma and peritoneal lavage was found to remain at low concentration in PLGA nanoparticles treated mice as well as ZnO nanoparticles during the 24 hour period. However, these were significantly increased in lipopolysaccharide (LPS) treated mice. Of these pro-inflammatory cytokines, IL-6 and IL-12p70 were produced at the highest concentration in the positive control group. The anti-inflammatory cytokines IL-10 and chemokines INF-γ, IL-4, IL-5 remained at normal levels in PLGA treated mice. IL-10 and INF-γ were significantly increased in LPS treated mice. MCP-1 was found to be significantly produced in all groups in the first hours, except the saline treated mice. These results provide the first report to detail the induction of cytokine production by PLGA nanoparticles engineered for oral applications.

Effects of protein binding on the biodistribution of PEGylated PLGA nanoparticles post oral administration.

The surface of nanoparticles is often functionalised with polymeric surfactants, in order to increase systemic circulation time. This has been investigated mainly for intravenously administered nanoparticles. This study aims to elucidate the effect of surface coating with various concentrations of polymeric surfactants (PEG and Pluronics F127) on the in vitro protein binding as well as the tissue biodistribution, post oral administration, of PLGA nanoparticles. The in vitro protein binding varied depending on the polymeric surfactant used. However, in vivo, 1% PEG and 1% Pluronics F127 coated particles presented similar biodistribution profiles in various tissues over seven days. Furthermore, the percentage of PEG and Pluronics coated particles detected in plasma was higher than that of uncoated PLGA particles, indicating that systemic circulation time can also be increased with oral formulations. The difference in the in vitro protein binding as a result of the different poloxamers used versus similar in vivo profiles of these particles indicates that in vitro observations for nanoparticles cannot represent or be correlated to the in vivo behaviour of the nanoparticles. Our results therefore suggest that more studies have to be conducted for oral formulations to give a better understanding of the kinetics of the particles.

Nanomedicine for respiratory diseases

Treatment of respiratory diseases and infections has proved to be a challenging task, with the incidence of these ailments increasing worldwide. Nanotechnology-based drug and gene delivery systems offer a possible solution to some of the shortfalls of the current treatment regimen. Nanobased drug delivery systems have revolutionised the field of pharmacotherapy by presenting the ability to alter the pharmacokinetics of the conventional drugs to extend the drug retention time, reduce the toxicity and increase the half-life of the drugs. Delivery of exogenous genes to the airway epithelium in vivo has been limited by several physiological barriers, resulting in the low success rate of these systems. With the advent of nanotechnology, DNA compacted with cationic polymers to produce nanoparticles has exhibited a significant increase in the transfection efficiencies. With nanoparticulate drug/gene delivery systems, specific cells can be targeted by functionalising the polymeric nanoparticles with ligands that allow the particles to dock at a specific site of the cell. In addition, polymeric systems allow for the cargo to be released in a controlled and stimuli-responsive manner. The advantages that nanoparticulate delivery systems present in the treatment of respiratory diseases and infections are summarised in this review.

Potential of Improving the Treatment of Tuberculosis Through Nanomedicine

Current treatment of tuberculosis is inadequate due to lengthy treatment course and drug-related toxicity. To address these setbacks, we developed a nanotechnology drug delivery system that can be administered in a single dose that maintains an active level of drug for at least a week. Polymeric poly(lactic-co-glycolic acid) nanoparticles of 200–300 nm were synthesized, with a drug encapsulation efficiency of 50–65% for isoniazid and rifampicin. The particles were taken up in vitro and in vivo and a slow release profile was observed in mice over 5 days. This study illustrates the feasibility of a sustained release system for tuberculosis treatment.

Nanomedicine in the Development of Drugs for Poverty-Related Diseases

The use of current treatments for poverty-related diseases (PRDs) is compromised due to factors such as toxicity and poor solubility leading to lowered bioavailability and thus reduced efficacy. In addition, there is lack of activity from the pharmaceutical industry due to the difficulty in refinancing the high development costs. Hence, new approaches have to be explored for the treatment of PRDs. Nanotechnology-based drug delivery systems (nanomedicine) offer a possible solution by presenting the ability to alter the pharmacokinetics of the conventional drugs to enhance bioavailability, increase the half-life of the drugs and reduce the toxicity. The advantages that nanomedicine-based drug delivery systems present in the treatment of PRDs and the progress of its application in Africa are summarised in this chapter. Nanodrug delivery systems seem to be a promising and viable strategy for improving treatment of PRDs and should urgently be considered in drug development programmes in Africa.