Formulation of Folate Receptor-Targeted Silibinin-Loaded Inhalable Chitosan Nanoparticles by the QbD Approach for Lung Cancer Targeted Delivery.

Aim: Targeted delivery of chemotherapeutics by functionalized nanoparticles exhibits a wonderful prospect for cancer treatment. The main objective of this research was to develop folate receptor-targeted silibinin (SB)-loaded inhalable polymeric nanoparticles (FA-CS-SB-NPs) for the treatment of lung cancer. Method: The qbD approach was implemented to prepare SB-loaded nanoparticles. Folic acid was conjugated by electrostatic conjugation in an optimized batch. The therapeutic potentials of formulations were determined using a lung cancer cell-bearing rat model. Result: Optimized formulation exhibited a spherical surface with a mean particle size of 275 ± 1.20 nm, a PDI of 0.234 ± 0.07, a ζ-potential of 32.50 ± 0.21, an entrapment efficiency of 75.52 ± 0.87%, and a CDR of 63.25 ± 1.21% at 48 h. Aerodynamic behaviors such as the mass median aerodynamic diameter (MMAD) and geometric size distribution (GSD) were found to be 2.75 ± 1.02 and 3.15 ± 0.88 µm, respectively. After 24 h of incubation with FA-CS-SB-NPs, the IC50 value was found to be 24.5 g/mL. FA-SB-CS-NPs maintained a significantly higher deposition of SB in lung tissues. Conclusions: Thus, the noninvasive nature and target specificity of FA-CS-SB-NPs pave the way for pulmonary delivery for treating lung cancer.

Neuroprotective potential of saroglitazar in 6-OHDA induced Parkinson's disease in rats.

Parkinson's disease (PD) is a neurodegenerative disorder that affects 2%-3% of the population worldwide. Clinical presentation of PD includes motor and non-motor symptoms. The interplay between pathogenic factors such as increased oxidative stress, neuroinflammation, mitochondrial dysfunction and apoptosis are responsible for neurodegeneration in PD. Intrastriatal administration of 6-hydroxy dopamine (6-OHDA) in rat brain provoked oxidative and nitrosative stress by decreasing endogenous antioxidants such as superoxide dismutase, catalase, glutathione, glutathione peroxidase and glutathione reductase. Consequently, interleukin-6, tumour necrosis-α, interferon-γ and cyclooxygenase-2 mediated neuroinflammation leads to mitochondrial dysfunction, involving inhibition of complex-II and IV activities, followed by apoptosis and degeneration of striatal dopaminergic neurons. Degeneration of dopaminergic neurons resulted in reduced dopamine turnover, consequently induced behavioural abnormalities in rats. Activation of peroxisome proliferator-activated receptors (PPARs) have protective role in PD by modulating response of antioxidant enzymes, neuroinflammation and apoptosis in various animal models of PD. Saroglitazar (SG) being dual PPAR-α/γ agonist activates both PPAR-α and PPAR-γ receptors and provide neuroprotection by reducing oxidative stress, neuroinflammation, mitochondrial dysfunction and apoptosis of dopaminergic cells in 6-OHDA induced PD in rats. Thereby, SG restored striatal histopathological damage and dopamine concentration in rat striatum, and behavioural alterations in rats. Thus, SG proved neuroprotective effects in rat model of PD. Potential benefits of SG in rat model of PD advocates to consider it for further preclinical and clinical evaluation.

Geraniol protects hippocampal CA1 neurons and improves functional outcomes in global model of stroke in rats.

Geraniol (GE), an acyclic monoterpene, is a chief constituent of essential oils of herbs and fruits. It possesses diverse pharmacological actions like antioxidant, anti-inflammatory, anti-apoptotic, and anti-parkinson. However, its neuroprotective potential in stroke is yet to be explored at large. The present study evaluated the neuroprotective potential of GE against the global model of cerebral ischemia/reperfusion (I/R)-injury in rats. Bilateral common carotid artery (BCCA) occlusion for 30 min followed by 7 days of reperfusion caused varied biochemical/enzymatic alterations viz. increase in levels of lipid peroxidation (LPO), nitric oxide (NO), xanthine oxidase (XO), and decrease in the levels of cerebroprotectives like superoxide dismutase (SOD), catalase (CAT), total thiols, and glutathione (GSH). GE-pretreatment markedly reversed these changes and restored the levels of protective enzymatic and non-enzymatic antioxidants near to normal compared to I/R group. Besides, GE treatment showed marked improvement in anxiety-related behavior and neuronal deficits in animals subjected to I/R injury. Moreover, 2,3,5-triphenyl tetrazolium chloride (TTC)-stained rat brain coronal sections and histopathological studies revealed neuronal protection against I/R-injury, as evidenced by a reduction in infarct area (%) and an increase in hippocampal CA1 neuronal density in the GE-treated groups. The results of this study revealed that GE exhibited potential neuroprotective activity by reducing oxidative stress and infarction area, and protecting hippocampal CA1 neurons against I/R-injury in the global stroke model in rats.

RP-HPLC method development, validation and pharmacokinetic applicability in preclinical evaluation of rhein treated with novel diacerein eutectics.

The current study represents a bioanalytical method for the estimation of rhein (Rh, an active metabolite of diacerein, DIA) in rats treated with novel DIA eutectics to investigate the pharmacokinetics of DIA. A simple protein precipitation technique was used to extract Rh and the internal standard (IS), p-aminobenzoic acid, injected into a Phenomenex Gemini C18 column. The separation was achieved by a gradient elution comprising ammonium acetate (10 mm; pH 3.0) and acetonitrile in an 18 min run time at a flow rate of 0.8 ml/min with retention times of 11.8 min (Rh) and 5.9 min (IS). The results revealed that the proposed method is linear over a range of 200-20,000 ng/ml (r2 > 0.9988) of Rh and is precise and accurate. The method was fully validated as per the US Food and Drug Administration guidelines and a pharmacokinetic study in rats was performed for Rh following oral administration of the pure DIA and newly developed eutectics. Therefore, the present method could be used to estimate DIA to illustrate a comparative pharmacokinetic analysis. This can also be applied to its related multicomponent formulations for future studies.

Lung cancer targeting efficiency of Silibinin loaded Poly Caprolactone /Pluronic F68 Inhalable nanoparticles: In vitro and In vivo study.

Silibinin (SB) is shown to have an anticancer properties. However, its clinical therapeutic effects have been restricted due to its low water solubility and poor absorption after oral administration. The aim of this study was to develop SB-loaded PCL/Pluronic F68 nanoparticles for pulmonary delivery in the treatment of lung cancer. A modified solvent displacement process was used to make nanoparticles, which were then lyophilized to make inhalation powder, Nanoparticles were characterized with DSC, FTIR,SEM and In vitro release study. Further, a validated HPLC method was developed to investigate the Biodistribution study, pharmacokinetic parameters. Poly Caprolactone PCL / Pluronic F68 NPs showed the sustained release effect up to 48 h with an emitted (Mass median Aerodynamic diameter)MMAD and (Geometric size distribution)GSD were found to be 4.235 ±0.124 and 1.958±1.23 respectively. More specifically, the SB Loaded PCL/Pluronic F 68 NPs demonstrated long circulation and successful lung tumor-targeting potential due to their cancer-targeting capabilities. SB Loaded PCL/Pluronic F68 NPs significantly inhibited tumour growth in lung cancer-induced rats after inhalable administration. In a pharmacokinetics study, PCL/ Pluronic F68 NPs substantially improved SB bioavailability, with a more than 4-fold rise in AUC when compared to IV administration. These findings indicate that SB-loaded PCL/PluronicF68 nanoparticles may be a successful lung cancer therapy delivery system.

Silibinin loaded inhalable solid lipid nanoparticles for lung targeting.

AIM: In the current study, efforts are being made to prepare Inhalable Silibinin loaded solid lipid nanoparticles (SLNs) with narrow size distribution with improved bioavailability. METHODS: SLNs were formulated by high shear homogenisation method SLNs were characterised, including Differential Scanning Calorimetry (DSC), Fourier transform infra-red spectroscopy (FTIR), particle size analysis, entrapment efficiency with Aerodynamic behaviour. The MTT assay was performed against A549 cell line, to measure their anticancer cell activity with In vivo study. RESULTS: Optimized formulation exhibited spherical surface with a mean particle size of 221 ± 1.251 nm, PI of 0.121 ± 0.081, zeta potential of -4.12 ± 0.744. Aerodynamic behaviour such as Mass median aerodynamic diameter (MMAD) and Geometric size distribution (GSD) were found to be 5.487 ± 0.072 and 2.321 ± 0.141 respectively proved formulation is suitable for inhalation. In vitro cellular efficacy against A549 cells, revealed that the optimised formulations were more effective and potent. CONCLUSION: The Inhalable SLNs approach was successfully engineered and administered to the lungs safely without causing any problems.

Ficus recemosa bark extract attenuates diabetic complications and oxidative stress in STZ-induced diabetic rats.

Context Ficus recemosa Linn. (Moraceae) has been reported as a natural folk medicine with diverse pathological activities such as antioxidant, antidiabetic, renoprotective and cardioprotective. Objective The present study evaluates the preventive effect of standardised ethanol extract of F. racemosa stem bark (EEFSB) on diabetic cardiomyopathy (DC) and diabetic nephropathy (DN). Materials and methods Animals were rendered diabetic by one time administration of STZ (45 mg kg(-1), i.v.) and, after 7 d, diabetic rats were randomised into four groups of eight rats each. EEFSB (200 and 400 mg kg(-1)) was administered to diabetic rats once daily for 8 weeks. Furthermore, the presence of phytochemicals was evaluated by HPTLC. Results Treatment with EEFSB markedly restores the blood glucose and lipid level (p < 0.001), also reduced creatinine kinase (p < 0.001), lactate dehydrogenase (p < 0.001), C-reactive protein (p < 0.001), creatinine (p < 0.001), blood urea nitrogen (p < 0.001), collagen (p < 0.05) and albumin (p < 0.001) levels. Reduced level of sodium (p < 0.001), creatinine (p < 0.001), albumin (p < 0.001) and malondialdehyde (p < 0.01) in heart and kidney tissue along with enhanced activities of superoxide dismutase (p < 0.001) and reduced glutathione (p < 0.001). Moreover, left ventricular hypertrophic index and cardiac hypertrophic index were markedly reduced by EEFSB treatment. Conclusion The findings of this study provided strong scientific evidence for the traditional use of F. racemosa and postulate protective effects against diabetes and its complications such as DC and DN.

Solasodine protects rat brain against ischemia/reperfusion injury through its antioxidant activity.

Ischemic stroke is the second leading cause of death worldwide. The major limitation of stroke management is the lack of clinically effective therapy. Antioxidants have been demonstrated as potent neuroprotective agents by enhancing the defense mechanism(s), whereas reducing the oxidative stress in the ischemic stroke models. In the present study, we evaluated neuroprotective potential of solasodine, an antioxidant glycoalkaloid of Solanum species, against global model of ischemia in rats. Ischemia/reperfusion (I/R)-injury produced marked elevation in lipid peroxidation (LPO) and nitric oxide (NO), whereas superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels were decreased in experimental animals. Prior administration of solasodine (100 and 200mg/kg, p.o.) significantly heightened SOD, CAT, GSH and total thiols, whereas reduced LPO and NO levels in the brain. Interestingly, brain coronal sectioning and histopathology studies revealed a marked reversal of I/R-provoked neuronal damage in the solasodine treatment groups. Taken together, our study, for the first time, demonstrates neuroprotective potential of solasodine against global ischemia-induced cerebral injury in experimental rats. We propose that the neuroprotection offered by solasodine could be attributed, at least in part, to its anti-oxidant property.