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Dengue virus (DENV) infection remains a formidable public health concern, causing significant fatalities worldwide. The unavailability of specific anti-DENV therapeutics and poor response towards dengue vaccine have impeded efforts to prevent and control this tropical disease, thereby, there is a pressing need for effective alternative therapeutics. Curcuma species including Curcuma aeruginosa have a long history of traditional use for the prevention and treatment of various ailments, including viral infections. While it is evident that several compounds isolated from these plants have antiviral activity against various viruses, their specific effects against DENV have not been thoroughly explored. The study aimed to investigate the potential of major compounds isolated from C. aeruginosa (demethoxycurcumin, curcumenol, furanodienone germacrone and zederone) in inhibiting DENV-2 NS2B-NS3 protease activity both in vitro and in silico. The results demonstrated that demethoxycurcumin (at 100 μM), furanodienone and germacrone (both at 25 μM) exhibited inhibitory effects on NS2B-NS3 protease activity comparable to aprotinin, a potent NS2B-NS3 protease inhibitor, albeit to a lesser extent. Importantly, these inhibitory concentrations did not adversely affect the viability of normal fibroblast cell line, L-929 cells, suggesting that the compounds' effects were specific to the protease inhibition. Further in silico molecular docking analyses indicated that demethoxycurcumin, furanodienone and germacrone displayed significant binding affinities with both DENV E protein and DENV NS2B-NS3 protease, corroborating their inhibitory activity observed in the protease inhibition assay. These promising findings collectively suggest that demethoxycurcumin, furanodienone and germacrone from C. aeruginosa merit further development as distinctive inhibitors for treating DENV infection. [ABSTRACT FROM AUTHOR]

Introduction: The classification of atovaquone (ATQ) as a BCS Class II drug illustrates its solubility challenges in the GIT that will affect its oral absorption and bioavailability. Among the polymers available for nanoparticles production, chitosan has demonstrated favorable properties, including biocompatibility and low toxicity. The objective of this study is to prepare and characterize chitosan nanoparticles as a carrier for ATQ with a specific aim for solubility enhancement. Methods: ATQ-loaded chitosan nanoparticles were prepared using the ionic gelation method. The formulations were characterized for particle size, polydispersity index (PDI), surface charge, encapsulation efficiency, FTIR spectroscopy, and in vitro drug release study in simulated gastric fluid (SGF; pH 1.2) and simulated intestinal fluid (SIF; pH 6.8). The stability of the nanoparticles was evaluated at 4°C, 25°C, and 40°C/75%RH for three months. Results: The physical properties of chitosan nanoparticles can be controlled by manipulating the components used in the formulation. The final formulation features: a particle size of 235.9 nm (± 4.9), PDI of 0.26 (± 0.02), zeta potential of +29.2 mV (± 1.1), and an encapsulation efficiency of 95.0% (± 1.0). In vitro drug release study showed a 7-fold and 4-fold increase in the solubility of ATQ in SGF and SIF respectively, as compared to the free drug. The aqueous nanoparticle formulations were stable for three months at 4°C and 25°C storage conditions. Conclusion: This study highlights the ability of chitosan nanoparticles to enhance the solubility of ATQ and potentially increase the bioavailability of ATQ in vivo. [ABSTRACT FROM AUTHOR]

Chitosan has been shown to have great potentials in various pharmaceuticals and biomedical applications, including drug delivery. Derived from chitin abundantly available in the shells of crustaceans such as crabs and shrimps, this naturally occurring polysaccharide is classified based on its molecular weight: low, medium or high. This study aimed to explore the production of chitosan nanoparticles (NP) and the influence of different factors on the physical properties of the NP produced. These factors were the concentrations of acetic acid, chitosan flakes and tripolyphosphate (TPP). The design of experiment (DoE) approach was used to determine the optimum conditions for the production of chitosan NP, with particle size (nm) and polydispersity index (PdI) being set as the responses. The chitosan flakes were solubilised in acetic acid at a specific concentration determined by the DoE before dropwise addition of TPP in an ice bath. The mixture was stirred at room temperature and subsequently centrifuged to remove the unformed materials, and then was spray-dried into powder. The size, surface charge, shape and morphology of the particles produced were characterised and infrared analysis was conducted. The results showed that the particles were spherical, slightly positively charged (ζ-potential: +2.89 at pH 7) and the infrared analysis displayed important peaks of the chitosan NP. The DoE results showed that not all combinations of parameters could produce NP; hence, determination of concentration for each parameter is essential. The equation produced by the DoE will be a useful guide to minimise error in this circumstance. In conclusion, the acetic acid and chitosan flakes concentrations were found to influence the particle size positively, whilst the increment in TPP concentration will adversely affect the particle size. Similar pattern of response was also observed for the PdI of the particles. The methods used in this study has successfully produced spherical particles, with evidence of interactions between TPP and chitosan in the NP as shown in the infrared spectrum. [ABSTRACT FROM AUTHOR]

Solid lipid nanoparticles of atovaquone (ATQ-SLN) were prepared by high shear homogenization method using tripalmitin, trilaurin, and Compritol 888 ATO as the lipid matrices and Phospholipon 90H, Tween 80, and poloxamer 188 as the surfactants. Optimization of the formulations was conducted using 6 sets of 24 full-factorial design based on four independent variables that were the number of homogenizing cycles, concentration of the lipid, concentration of the co-surfactant, and concentration of the main surfactant. The dependent variables were particle size and polydispersity index (PdI). The homogenizing cycles showed a negative influence on the dependent variables which reduced both the particle size and the PdI value. Moreover, a combination of certain percentages of the main surfactant and co-surfactant also showed a negative influence that reduced both the particle size and PdI value. Selected formulations from each design were further characterized for the entrapment efficiency and yield. The optimised formulation of ATQ-SLN consisted of trilaurin, Phospholipon 90H and Tween 80 with a particle size of 89.4 ± 0.2 nm and entrapment efficiency of 83.0 ± 1.7%. The in-vitro release evaluation of the formulation showed a complete and immediate release of ATQ from the SLN that could be a solution to improve the poor aqueous solubility and hence poor bioavailability of the drug. [ABSTRACT FROM AUTHOR]

Phytochemicals have shown potentials in preventing and treating various lung diseases, including asthma and lung cancer. However, their use has been hampered by limitations such as poor water solubility and instability. Nanoformulations, which include organic nanoparticles (e.g. liposomes) and inorganic nanoparticles (e.g. gold/silver nanoparticles) have potential to enhance drug solubility and subsequently increase their absorption and bioavailability. These drug formulations can be administered via various routes such as oral, intravenous, and pulmonary. This review highlights the potential of some phytochemicals in managing lung diseases and discusses the mechanism of actions of these phytochemicals and the impact of using the nanoformulations to deliver phytochemicals, particularly through pulmonary route. While pre-clinical studies have shown promising therapeutic activities of phytochemicals-loaded nanoformulations, further research is required. In conclusion, the application of phytochemicals and nanoformulations as drug delivery systems could be a promising approach to facilitate optimal therapy for lung diseases. [ABSTRACT FROM AUTHOR]

Solid lipid nanoparticles of atovaquone (ATQ-SLN) were prepared by high shear homogenization method using tripalmitin, trilaurin, and Compritol 888 ATO as the lipid matrices and Phospholipon 90H, Tween 80, and poloxamer 188 as the surfactants. Optimization of the formulations was conducted using 6 sets of 2(4) full-factorial design based on four independent variables that were the number of homogenizing cycles, concentration of the lipid, concentration of the co-surfactant, and concentration of the main surfactant. The dependent variables were particle size and polydispersity index (PdI). The homogenizing cycles showed a negative influence on the dependent variables which reduced both the particle size and the PdI value. Moreover, a combination of certain percentages of the main surfactant and co-surfactant also showed a negative influence that reduced both the particle size and PdI value. Selected formulations from each design were further characterized for the entrapment efficiency and yield. The optimised formulation of ATQ-SLN consisted of trilaurin, Phospholipon 90H and Tween 80 with a particle size of 89.4 ± 0.2 nm and entrapment efficiency of 83.0 ± 1.7%. The in-vitro release evaluation of the formulation showed a complete and immediate release of ATQ from the SLN that could be a solution to improve the poor aqueous solubility and hence poor bioavailability of the drug.

The delivery of drugs and bioactive compounds via the lymphatic system is complex and dependent on the physiological uniqueness of the system. The lymphatic route plays an important role in transporting extracellular fluid to maintain homeostasis and in transferring immune cells to injury sites, and is able to avoid first-pass metabolism, thus acting as a bypass route for compounds with lower bioavailability, ie, those undergoing more hepatic metabolism. The lymphatic route also provides an option for the delivery of therapeutic molecules, such as drugs to treat cancer and human immunodeficiency virus, which can travel through the lymphatic system. Lymphatic imaging is useful in evaluating disease states and treatment plans for progressive diseases of the lymph system. Novel lipid-based nanoformulations, such as solid lipid nanoparticles and nanostructured lipid carriers, have unique characteristics that make them promising candidates for lymphatic delivery. These formulations are superior to colloidal carrier systems because they have controlled release properties and provide better chemical stability for drug molecules. However, multiple factors regulate the lymphatic delivery of drugs. Prior to lymphatic uptake, lipid-based nanoformulations are required to undergo interstitial hindrance that modulates drug delivery. Therefore, uptake and distribution of lipid-based nanoformulations by the lymphatic system depends on factors such as particle size, surface charge, molecular weight, and hydrophobicity. Types of lipid and concentration of the emulsifier are also important factors affecting drug delivery via the lymphatic system. All of these factors can cause changes in intermolecular interactions between the lipid nanoparticle matrix and the incorporated drug, which in turn affects uptake of drug into the lymphatic system. Two lipid-based nanoformulations, ie, solid lipid nanoparticles and nanostructured lipid carriers, have been administered via multiple routes (subcutaneous, pulmonary, and intestinal) for targeting of the lymphatic system. This paper provides a detailed review of novel lipid-based nanoformulations and their lymphatic delivery via different routes, as well as the in vivo and in vitro models used to study drug transport in the lymphatic system. Physicochemical properties that influence lymphatic delivery as well as the advantages of lipid-based nanoformulations for lymphatic delivery are also discussed.