RESUMO
The purpose of this study was to assess the parameters of doxorubicin (DOX) loaded lipid polymer hybrid nanoparticles (LPHNs) formulation development, and then the bioavailability of DOX were determined in the rabbit model, in order to evaluate the intrinsic outcome of dosage form improvement after the oral administration. LPHNs were prepared by combine approach, using both magnetic stirring and probe sonication followed by its characterization in terms of size-distribution (Zeta Size), entrapment efficiency (EE), loading capacity, and the kinetics of DOX. LPHNPs were further characterized by using scanning electron microscopy (SEM), powder X-Ray diffractometry (P-XRD), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), in vitro and in vivo studies. The molecular modeling was determined through the density functional theory (DFT) simulations and interactions. DOX loaded and unloaded LPHNs were administered orally to the rabbits for bioavailability and pharmacokinetic parameters determinations. The plasma concentration of DOX was determined through high performance liquid chromatography (HPLC). The average size of DOX-loaded LPHNs was 121.90 ± 3.0 nm. The drug loading of DOX was 0.391% ± 0.01 of aqueous dispersion, where its encapsulation efficiency was 95.5% ± 1.39. After oral administration of the DOX-LPHNs, the area under the plasma drug concentration-time curve (AUC) improved about 2-folds comparatively (p < 0.05). DFT simulations were used to understand the interactions of polymers with different sites of DOX molecule. The larger negative binding energies (-9.33 to -18.53 kcal/mol) of the different complexes evince that the polymers have stronger affinity to bind with the DOX molecule while the negative values shows that the process is spontaneous, and the synthesis of DOX-LPHNs is energetically favorable. It was concluded that DOX-LPHNs provides a promising new formulation that can enhance the oral bioavailability, which have optimized compatibilities and improve the pharmacokinetic of DOX after oral administration.
RESUMO
Industrialization plays a vital role in the development of a country's economy. However, it also adversely affects the environment by discharging various unwanted and harmful substances such as heavy metals into the surface and subsurface aquifers. The current research work investigates the identification, characterization, and evaluation of specific heavy metals in industrial wastewater (IWW) and different composite samples of soil and vegetables (onion, pumpkin, lady finger, and green pepper) collected from selected agricultural fields irrigated with canals fed IWW in Mingora city of Swat (Pakistan). Obtained results were compared with the tube well water irrigated soil and vegetables grown in it. Heavy metals accumulation was tested through wet digestion method and atomic absorption spectrophotometry (AAS). The metal transfer factor (MTF) of heavy metals from soil to vegetables was also determined along with the health index (HI) to assess the potential health risk of the metals towards consumers using Monte Carlo simulation technique. Analysis of water samples showed that the concentration in mg l-1 of heavy metals in IWW follows the trend Fe (6.72) > Cr (0.537) > Pb (0.393) > Co (0.204) > Mn (0.125) > Ni (0.121). Analysis of the soil samples irrigated with IWW followed the order of Fe (47.27) > Pb (2.92) > Cr (2.90) >Ni (1.02) > Mn (0.90) > Co (0.68) and Fe (17.12) > Pb (2.12) > Cr (2.03) >Ni (0.76) > Co (0.49) > Mn (0.23) irrigated with TWW. Heavy metals concentration values found in soil irrigated with IWW were higher than the soil irrigated with TWW. Similar trends were found for agricultural produces grown on soil irrigated with IWW and found higher than the normal allowable WHO limits, indicating higher possibilities of health risks if continuously consumed. MTF values were found higher than 1 for ladyfinger and green pepper for Pb intake and pumpkin for Mn intake. The current study suggests the continuous monitoring of soil, irrigation water and agricultural products to prevent heavy metals concentration beyond allowable limits, in the food chain. Thus, concrete preventive measures must be taken to reduce heavy metal accumulation through wastewater irrigation to protect both human and animal health in the study area of Mingora Swat Pakistan.
