In Vivo Evaluation of Praziquantel-Loaded Solid Lipid Nanoparticles against S. mansoni Infection in Preclinical Murine Models.

This study aimed to develop and assess the long-term stability of drug-loaded solid lipid nanoparticles (SLNs). The SLNs were designed to extend the release profile, overcome the problems of bioavailability and solubility, investigate toxicity, and improve the antischistosomal efficacy of praziquantel. The aim was pursued using solvent injection co-homogenization techniques to fabricate SLNs in which Compritol ATO 888 and lecithin were used as lipids, and Pluronic F127 (PF127) was used as a stabilizer. The long-term stability effect of the PF127 as a stabilizer on the SLNs was evaluated. Dynamic light scattering (DLS) was used to determine the particle size, stability, and polydispersity. The morphology of the SLNs was examined through the use of transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The chemical properties, as well as the mechanical, thermal, and crystal behaviours of SLNs were evaluated using FTIR, ElastoSens Bio2, XRPD, DSC, and TGA, respectively. SLNs with PF127 depicted an encapsulation efficiency of 71.63% and a drug loading capacity of 11.46%. The in vitro drug release study for SLNs with PF127 showed a cumulative release of 48.08% for the PZQ within 24 h, with a similar release profile for SLNs' suspension after 120 days. DLS, ELS, and optical characterization and stability profiling data indicate that the addition of PF127 as the surfactants provided long-term stability for SLNs. In vitro cell viability and in vivo toxicity evaluation signify the safety of SLNs stabilized with PF127. In conclusion, the parasitological data showed that in S. mansoni-infected mice, a single (250 mg/kg) oral dosage of CLPF-SLNs greatly improved PZQ antischistosomal efficacy both two and four weeks post-infection. Thus, the fabricated CLPF-SLNs demonstrated significant efficiency inthe delivery of PZQ, and hence are a promising therapeutic strategy against schistosomiasis.

Optimal control of the coronavirus pandemic with both pharmaceutical and non-pharmaceutical interventions.

Coronaviruses are types of viruses that are widely spread in humans, birds, and other mammals, leading to hepatic, respiratory, neurologic, and enteric diseases. The disease is presently a pandemic with great medical, economical, and political impacts, and it is mostly spread through physical contact. To extinct the virus, keeping physical distance and taking vaccine are key. In this study, a dynamical transmission compartment model for coronavirus (COVID-19) is designed and rigorously analyzed using Routh-Hurwitz condition for the stability analysis. A global dynamics of mathematical formulation was investigated with the help of a constructed Lyapunov function. We further examined parameter sensitivities (local and global) to identify terms with greater impact or influence on the dynamics of the disease. Our approach is data driven to test the efficacy of the proposed model. The formulation was incorporated with available confirmed cases from January 22, 2020, to December 20, 2021, and parameterized using real-time series data that were collected on a daily basis for the first 705 days for fourteen countries, out of which the model was simulated using four selected countries: USA, Italy, South Africa, and Nigeria. A least square technique was adopted for the estimation of parameters. The simulated solutions of the model were analyzed using MAPLE-18 with Runge-Kutta-Felberg method (RKF45 solver). The model entrenched parameters analysis revealed that there are both disease-free and endemic equilibrium points. The solutions depicted that the free equilibrium point for COVID-19 is asymptotic locally stable, when the epidemiological reproduction number condition ( R 0 < 1 ) . The simulation results unveiled that the pandemic can be controlled if other control measures, such as face mask wearing in public areas and washing of hands, are combined with high level of compliance to physical distancing. Furthermore, an autonomous derivative equation for the five-dimensional deterministic was done with two control terms and constant rates for the pharmaceutical and non-pharmaceutical strategies. The Lagrangian and Hamilton were formulated to study the model optimal control existence, using Pontryagin's Maximum Principle describing the optimal control terms. The designed objective functional reduced the intervention costs and infections. We concluded that the COVID-19 curve can be flattened through strict compliance to both pharmaceutical and non-pharmaceutical strategies. The more the compliance level to physical distance and taking of vaccine, the earlier the curve is flattened and the earlier the economy will be bounce-back.

In silico inhibition of SGTP4 as a therapeutic target for the treatment of schistosomiasis.

Schistosomiasis is an infectious tropical disease caused by parasitic flatworm of the genus Schistosoma. This debilitating disease chronically infects about 200 million people globally and management relies on chemotherapy. Unfortunately, the solely available schistosomicide (praziquantel) against all forms of adult schistosmes has been faced with numerous drawbacks. Thus, there is an urgent need to design and develop a new regimen for schistosomiasis. In light of this, the current study focuses on inhibiting the schistosome glucose transporter 4 (SGTP4) as a therapeutic candidate for schistosomiasis. Several studies have revealed that Schistosoma parasites require an adequate amount of energy/glucose to survive. We modelled the 3D structure and subsequently used the homology model for docking with praziquantel (PZQ), Licochalcone A, Licarin and Harmonine. The docked complexes were subjected to molecular dynamics using Desmond system of Schrodinger software. Furthermore, the pharmacokinetic parameters of the ligands were investigated using the QikProp tool in the Schrodinger-2019-4 software suite. After performing all the computational analysis, our findings reveal that all four ligands were able to inhibit SGTP4 effectively through the higher glide G score (dock score) of -5.8 (-5.8), -6.5 (-6.4), -7.3 (-7.3) and -4.9 (-4.9) in kcal/mol for praziquantel, licochalcone A, licarin and harmonine respectively against the protein. The molecular simulation further confirmed that the stability of the complexes formed between the ligands and protein is excellent. More so, all the ligands fulfilled oral drugability of both the Lipinski's rule of five and Veber's rules.The findings in this present study provide new useful insights for the design of drugs which can serve as an alternative to praziquantel in the treatment of schistosomiasis through the inhibition of SGTP4.Communicated by Freddie R. Salsbury.

In Vivo Evaluation of an Antibody-Functionalized Lipoidal Nanosystem for Schistosomiasis Intervention.

This study employed nanotechnological techniques to design and develop a praziquantel nanoliposomal (NLP) system and surface-functionalized the NLP with anti-calpain antibody (anti-calpain-NLP) for targeted praziquantel (PZQ) delivery in the treatment of schistosomiasis. Anti-calpain-NLPs were prepared and validated for their physicochemical parameters, in vitroand in vivotoxicity, drug entrapment efficiency (DEE), drug loading capacity (DLC), drug release, and parasitological cure rate. The particle sizes for the formulated nanoliposomes ranged from 88.3 to 92.7 nm (PDI = 0.17-0.35), and zeta potential ranged from -20.2 to -31.9 mV. The DLC and DEE ranged from 9.03 to 14.16 and 92.07 to 94.63, respectively. The functionalization of the nanoliposome surface was stable, uniform, and spherical. Fourier-transform infrared (FTIR), thermal behavior and X-ray powder diffraction (XRPD) analysis confirmed that the anti-calpain antibody and PZQ were attached to the surface and the nanoliposomes inner core, respectively. The drug sustained release was shown to be 93.2 and 91.1% within 24 h for NLP and anti-calpain-NLP, respectively. In thein vitroanalysis study, the nanoliposome concentrations range of 30 to 120 µg/mL employed revealed acceptable levels of cell viability, with no significant cytotoxic effects on RAW 264.7 murine macrophage as well as 3T3 human fibroblast cells. Biochemical markers and histopathological analysis showed that the formulated nanoliposomes present no or minimal oxidative stress and confer hepatoprotective effects on the animals. The cure rate of the anti-calpain-NLP and PZQ was assessed by parasitological analysis, and it was discovered that treatment with 250 mg/kg anti-calpain-NLP demonstrated greater activity on the total worm burden, and ova count for both the juvenile and adult schistosomes in the intestine and liver of infected mice. The findings so obtained supported the ability of oral anti-calpain-NLP to target young and adult schistosomes in the liver and porto-mesenteric locations, resulting in improved effectiveness of PZQ.

Synthesis and therapeutic delivery approaches for praziquantel: a patent review (2010-present).

INTRODUCTION: : Among all the anti-schistosomal drugs, praziquantel has been the most widely used. However, some major challenges have been faced using the drug in the treatment of schistosome infections. AREAS COVERED: : Several approaches used in the synthesis of praziquantel aimed at reducing the time and cost of production, the toxicity and experimental harsh conditions are discussed. Also, patented methods involved in the pharmaceutical reformulation of praziquantel in the treatment of diverse endoparasitic infestations are reported. Additionally, future perspectives in terms of nanomedicine approach in the formulation of praziquantel are highlighted. EXPERT OPINION: : Lipid-based nanosystems (LBNSs) formulations can be used to overcome the shortcomings associated with the use of praziquantel in the schistosomiasis treatment due to their amphipathic nature. This could be a promising vehicle for the delivery of praziquantel, which could in turn improve the bioavailability, as well as reduce the frequent dose of the drug and improve patient compliance. This may sustain the release of the drug and improve the rapid conversion of the drug into inactive metabolite due to rapid metabolism. Additionally, LBNSs approach could increase and improve the lipophilicity of the drug, which could make it easier to interact with the hydrophobic cores of the worm tegument.

Prospects of nanodentistry for the diagnosis and treatment of maxillofacial pathologies and cancers.

Despite the commendable milestones achieved in molecular maxillofacial pathology in the last decade, there remains a paucity of utilization of ancillary nanomolecular tools that complement the omics-based approaches. As the advent of omics science transforms our understanding of tumour biology from a phenomenological to a complex network (systems-oriented) paradigm, several ancillary tools have emerged to improve the scope of individualized medicine. Targeted nano drug delivery systems have significantly reduced toxicity of chemotherapeutic agents in a precise manner. Many conventional cancer therapies are limited in efficacy and this has led to the emergence of nanomedical innovations. Despite the success of nanomedicine, a major challenge that persists is tumour heterogeneity and biological complexity. A good understanding of the interaction between inorganic nanoparticles and the biological systems has led to the development of better tools for individualized medicine. Tools such as the composite organic-inorganic nanoparticles (COINs) and the quantum dots (QD) have significantly improved the identification and quantification of disease biomarkers, histopathological detection methods, as well as improving the clinical translation and utility of these nanomaterials. Nanomedicine has lent credence to several multipronged theranostic applications in medicine, and this has improved the medical practice tremendously. Despite the palpable influence of nanomedicine on the delivery of individualized medical therapies, the term "nanodentistry" remains in the background without much hype, albeit some progress has been made in this area. Hence, this review discusses the potential and challenges of nanodentistry in the diagnosis and treatment of maxillofacial pathologies, particularly cancer in resource-limited settings.