Acyclovir-Loaded Solid Lipid Nanoparticles: Optimization, Characterization and Evaluation of Its Pharmacokinetic Profile.

Acyclovir is an antiviral drug used for the treatment of herpes simplex virus infection. Its oral bioavailability is low; therefore, frequent and high doses are prescribed for optimum therapeutic efficacy. Moreover, the current therapeutic regimen of acyclovir is associated with unwarranted adverse effects, hence prompting the need for a suitable drug carrier to overcome these limitations. This study aimed to develop solid lipid nanoparticles (SLNs) as acyclovir carriers and evaluate their in vivo pharmacokinetic parameters to prove the study hypothesis. During the SLN development process, response surface methodology was exploited to optimize the composition of solid lipid and surfactant. Optimum combination of Biogapress Vegetal 297 ATO and Tween 80 was found essential to produce SLNs of 134 nm. The oral bioavailability study showed that acyclovir-loaded SLNs possessed superior oral bioavailability when compared with the commercial acyclovir suspension. The plasma concentration of acyclovir-loaded SLNs was four-fold higher than the commercial suspension. Thus, this investigation presented promising results that the method developed for encapsulation of acyclovir offers potential as an alternative pathway to enhance the drug's bioavailability. In conclusion, this study exhibited the feasibility of SLNs as an oral delivery vehicle for acyclovir and therefore represents a new promising therapeutic concept of acyclovir treatment via a nanoparticulate drug delivery system.

IL35 modulation altered survival, cytokine environment and histopathological consequences during malaria infection in mice.

BACKGROUND: The immune modulating potential of IL-35 in multiple human disorders has been reported. Consequent upon the recognition of inflammatory cytokine activation and its preponderance for mediating pathology during malaria infection, the study aimed to characterize the expression and functional contribution(s) of IL-35 in Plasmodium berghei (strain ANKA) infected mice. METHODS: Plasmodium berghei infection in male ICR mice was used as the rodent model of choice. The time course of IL-35 expression in the systemic circulation and tissues of P. berghei infected mice as well as their healthy control counterparts was assessed by enzyme linked immunosorbent assay and immunohistochemistry respectively. The effect of modulating IL-35 by recombinant IL-35 protein or neutralizing anti-Epstein-Barr virus-induced gene 3 antibody on the cytokine environment during P. berghei infection was assessed by flow cytometry. Furthermore, the influence of modulating IL-35 on histopathological hallmarks of malaria and disease progression was evaluated. RESULTS: Interleukin-35 was significantly up regulated in serum and tissues of P. berghei infected mice and correlated with parasitaemia. Neutralization of IL-35 significantly enhanced the release of IFN-γ, decreased the expression of IL-6 and decreased parasitaemia patency. Neutralization of IL-35 was also associated with a tendency towards increased survival as well as the absence of pathological features associated with malaria infection unlike recombinant IL-35 protein administration which sustained a normal course of infection and unfavourable malaria associated histological outcomes in P. berghei infected mice. CONCLUSION: These results indicate the involvement of IL-35 in P. berghei induced malaria infection. IL-35 neutralization strategies may represent viable therapeutic modalities beneficial for the resolution of malaria infection.

The Role, Involvement and Function(s) of Interleukin-35 and Interleukin-37 in Disease Pathogenesis.

The recently identified cytokines-interleukin (IL)-35 and interleukin (IL)-37-have been described for their anti-inflammatory and immune-modulating actions in numerous inflammatory diseases, auto-immune disorders, malignancies, infectious diseases and sepsis. Either cytokine has been reported to be reduced and in some cases elevated and consequently contributed towards disease pathogenesis. In view of the recent advances in utilizing cytokine profiles for the development of biological macromolecules, beneficial in the management of certain intractable immune-mediated disorders, these recently characterized cytokines (IL-35 and IL-37) offer potential as reasonable targets for the discovery of novel immune-modulating anti-inflammatory therapies. A detailed comprehension of their sophisticated regulatory mechanisms and patterns of expression may provide unique opportunities for clinical application as highly selective and target specific therapeutic agents. This review seeks to summarize the recent advancements in discerning the dynamics, mechanisms, immunoregulatory and anti-inflammatory actions of IL-35 and IL-37 as they relate to disease pathogenesis.