IntroductionTuberculosis (TB) is the single largest infectious disease which requires a prolonged treatment regime with multiple drugs. The present treatment for TB includes frequent administration of a combination of four drugs for a duration of 6 months. This leads to patient’s noncompliance, in addition to developing drug-resistant strains which makes treatment more difficult. The formulation of drugs with biodegradable polymeric nanoparticles (NPs) promises to overcome this problem.Materials and methodsIn this study, we focus on two important drugs used for TB treatment – rifampicin (RIF) and isoniazid (INH) – and report a detailed study of RIF-loaded poly lactic-co-glycolic acid (PLGA) NPs and INH modified as INH benz-hydrazone (IH2) which gives the same therapeutic effect as INH but is more stable and enhances the drug loading in PLGA NPs by 15-fold compared to INH. The optimized formulation was characterized using particle size analyzer, scanning electron microscopy and transmission electron microscopy. The drug release from NPs and stability of drug were tested in different pH conditions.ResultsIt was found that RIF and IH2 loaded in NPs release in a slow and sustained manner over a period of 1 month and they are more stable in NPs formulation compared to the free form. RIF- and IH2-loaded NPs were tested for antimicrobial susceptibility against Mycobacterium tuberculosis H37Rv strain. RIF loaded in PLGA NPs consistently inhibited the growth at 70% of the minimum inhibitory concentration (MIC) of pure RIF (MIC level 1 µg/mL), and pure IH2 and IH2-loaded NPs showed inhibition at MIC equivalent to the MIC of INH (0.1 µg/mL).ConclusionThese results show that NP formulations will improve the efficacy of drug delivery for TB treatment.
Objective: The objective of the study was to develop and validate a simple and reproducible reverse phase high pressure liquid chromatography (RP-HPLC) method for hydrophilic drug isoniazid (INH) to apply for the analysis of the INH in nanoparticle drug formulations. Furthermore, to estimate simultaneously rifampicin (RIF) and INH in combined form.
Methods:Isocratic elution with 10 minutes runtime on a C-18 Luna, 5 µ, 100Å, 150 mm column, methanol, and water as mobile phase with detection wavelength at 268 nm was used. INH nanoformulations were prepared by double emulsion solvent evaporation technique. Quantitative analysis of encapsulated drug was estimated via developed RP-HPLC method. Simultaneous estimation for the two drugs was carried out by gradient elution. All chromatographic separation and estimations were obtained on Shimadzu HPLC system.
Results:INH eluted with a short retention time (RT) of 4.06 minutes. Method showed good linearity in the range of concentrations 0.01-100 µg/ml. The limit of detection (LOD) and quantification (LOQ) for INH was 0.03 and 0.12 µg/mL, respectively, and developed method has been successfully applied for the analysis of drugs in nanoparticle formulations. Simultaneous estimation of antitubercular drugs INH and RIF showed two separate peaks within specified runtime.
Conclusion:Developed method showed good resolved peaks. Since the RT is short, in a shorter duration more samples could be completed and developed method will be easy for analyzing greater number of samples. Analysis of nanoformulation results have shown that this method is simple, reliable, reproducible, hence can be applied for drug delivery analysis.
A pandemic disease, COVID‐19, affecting over 253 million and 5.1 million deaths reported as on November 2021 from across the globe. The worst hit pandemic since a century. Scientists around the world are working towards the development of drugs for its treatment. Several existing antiviral medications have been tried for the same. Among these, Favipiravir, a broad‐spectrum antiviral drug originally developed to treat influenza, shows noted activity against an ample range of RNA viruses. It is an oral antiviral drug with good bioavailability found to be effective in the treatment of COVID‐19. This drug has acquired FDA manifestation for drug‐resistant Influenza as it has confirmed its safety profile. There has been growing evidence that it helps in early viral clearance and speedy symptomatic relief against COVID‐19. This review attempts to provide synthetic methods of favipiravir, mechanism of action and its importance in the treatment of COVID‐19 and other viruses.
In drug discovery, the hybridization of bioactive pharmacophores is a powerful tool for targeting enzymes involved in cancer and microbial cell growth. A combination of 1,3,4‐oxadiazole and isobenzofuran may improve the antitumor and antimicrobial properties of the hybrid molecules. A series of hybrid molecules having 1,3,4‐oxadiazole and isobenzofuran were synthesized and structural characterization was done by FT‐IR, 1H‐NMR, 13C‐NMR, and mass spectrometry. Molecular docking studies were performed to investigate binding interactions of compounds with proteins (PDB NO: 2R3J and 1GII), and the results were consistent with in vitro anticancer data. All the synthesized compounds were tested for antimicrobial activity against S. aureus, E. faecalis (Gram‐positive) and E. coli and P. aeruginosa (Gram‐negative) bacterial strains. Among the synthesized compounds, 7a and 7b displayed good activity against the tested bacterial strains. Also, compounds were tested for their anti‐tumor activity against breast cancer (MCF‐7) and colon cancer (HCT‐116) cell lines via SRB assay. In comparison to doxorubicin (1.14 μM), hybrids 7e (4.32 μM), 7f (4.15 μM), 7g (4.66 μM), and 7h (4.83 μM) demonstrated comparable IC50 value against the HCT 116 cell line.
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