Selective delivery of oxaliplatin to tumor tissue by nanocarrier system enhances overall therapeutic efficacy of the encapsulated oxaliplatin.

Oxaliplatin (trans-l-diaminocyclohexane oxalatoplatinum; l-OHP), a third-generation platinum antitumor drug, is currently approved in combination with 5-flurouracil (5-FU)/leucovorin (FOLFOX) for standard first- and second-line treatment of metastatic or advanced-stage colorectal cancer. Despite l-OHP's better tolerability in comparison with other platinum compounds such as cisplatin and carboplatin, its clinical efficiency is limited by the dose-limiting side effects including cumulative neurotoxicity and acute dysesthesias. In addition, like other platinum chemotherapeutic agents, l-OHP therapy is limited by reduced accumulation levels in tumor tissues, nonselective accumulation in healthy organs and/or tissues, inactivation by conjugation with glutathione, and the development of drug resistance. Accordingly, successful outcome of cancer treatment using l-OHP requires selective delivery of a relatively high concentration of the drug to tumor tissues. In this review we focus on utilization of different drug-delivery vehicles such as liposomes, polymeric nanocarriers, and carbon nanotubes in enhancing selective delivery of l-OHP to tumor tissues and consequently improving overall efficacy of l-OHP-containing drug-delivery systems.

Spanlastic-laden nanogel as a plausible platform for dermal delivery of bimatoprost with superior cutaneous deposition and hair regrowth efficiency in androgenic alopecia.

Bimatoprost (BIM) is a prostaglandin F2α analogs originally approved for the treatment of glaucoma and ocular hypertension. Recent studies have highlighted its potential to boost hair growth. The objective of this investigation is to challenge the potential of spanlastics (SLs) as a surfactant-based vesicular system for promoting the cutaneous delivery of BIM for the management of alopecia. BIM-loaded spanlastics (BIM-SLs), composed of Span as the main vesicle component and Tween as the edge activator, were fabricated by ethanol injection method. The formulated BIM-SLs were optimized by 23 full factorial design. The optimized formula (F1) was characterized for entrapment efficiency, surface charge, vesicle size, and drug release after 12 h (Q12h). The optimized formula (F1) exhibited high drug entrapment efficiency (83.1 ± 2.1%), appropriate zeta potential (-19.9 ± 2.1 mV), Q12h of 71.3 ± 5.3%, and a vesicle size of 364.2 ± 15.8 nm, which favored their cutaneous accumulation. In addition, ex-vivo skin deposition studies revealed that entrapping BIM within spanlastic-based nanogel (BIM-SLG) augmented the dermal deposition of BIM, compared to naïve BIM gel. Furthermore, in vivo studies verified the efficacy of spanlastic vesicles to boost the cutaneous accumulation of BIM compared to naive BIM gel; the AUC0-12h of BIM-SLG was 888.05 ± 72.31 µg/mL.h, which was twice as high as that of naïve BIM gel (AUC0-12h 382.86 ± 41.12 µg/mL.h). Intriguingly, BIM-SLG outperforms both naïve BIM gel and commercial minoxidil formulations in stimulating hair regrowth in an androgenetic alopecia mouse model. Collectively, spanlastic vesicles might be a potential platform for promoting the dermal delivery of BIM in managing alopecia.

Nano-Formulating Besifloxacin and Employing Quercetin as a Synergizer to Enhance the Potency of Besifloxacin against Pathogenic Bacterial Strains: A Nano-Synergistic Approach.

The present study applied a nano-synergistic approach to enhance besifloxacin's potency via nano-formulating besifloxacin on gold nanoparticles (Besi-AuNPs) and adding quercetin as a natural synergistic compound. In fact, a one-pot AuNP synthesis approach was applied for the generation of Besi-AuNPs, where besifloxacin itself acted as a reducing and capping agent. Characterization of Besi-AuNPs was performed by spectrophotometry, DLS, FTIR, and electron microscopy techniques. Moreover, antibacterial assessment of pure besifloxacin, Besi-AuNPs, and their combinations with quercetin were performed on Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. UV-spectra showed a peak of AuNPs at 526 nm, and the electron microscopy-based size was estimated to be 15 ± 3 nm. The effective MIC50 concentrations of besifloxacin after loading on AuNPs were reduced by approximately 50% against the tested bacterial strains. Interestingly, adding quercetin to Besi-AuNPs further enhanced their antibacterial potency, and isobologram analysis showed synergistic potential (combination index below 1) for different quercetin and Besi-AuNP combinations. However, Besi-AuNPs and quercetin combinations were most effective against Gram-positive S. aureus in comparison to Gram-negative P. aeruginosa and E. coli. Their potent activity against S. aureus has its own clinical significance, as it is one the main causative agents of ocular infection, and besifloxacin is primarily used for treating infectious eye diseases. Thus, the outcomes of the present study could be explored further to provide better medication for eye infections caused by resistant pathogens.

Antibiotic-Loaded Gold Nanoparticles: A Nano-Arsenal against ESBL Producer-Resistant Pathogens.

The advent of new antibiotics has helped clinicians to control severe bacterial infections. Despite this, inappropriate and redundant use of antibiotics, inadequate diagnosis, and smart resistant mechanisms developed by pathogens sometimes lead to the failure of treatment strategies. The genotypic analysis of clinical samples revealed that the rapid spread of extended-spectrum ß-lactamases (ESBLs) genes is one of the most common approaches acquired by bacterial pathogens to become resistant. The scenario compelled the researchers to prioritize the design and development of novel and effective therapeutic options. Nanotechnology has emerged as a plausible groundbreaking tool against resistant infectious pathogens. Numerous reports suggested that inorganic nanomaterials, specifically gold nanoparticles (AuNPs), have converted unresponsive antibiotics into potent ones against multi-drug resistant pathogenic strains. Interestingly, after almost two decades of exhaustive preclinical evaluations, AuNPs are gradually progressively moving ahead toward clinical evaluations. However, the mechanistic aspects of the antibacterial action of AuNPs remain an unsolved puzzle for the scientific fraternity. Thus, the review covers state-of-the-art investigations pertaining to the efficacy of AuNPs as a tool to overcome ESBLs acquired resistance, their applicability and toxicity perspectives, and the revelation of the most appropriate proposed mechanism of action. Conclusively, the trend suggested that antibiotic-loaded AuNPs could be developed into a promising interventional strategy to limit and overcome the concerns of antibiotic-resistance.

Enhancement of Vancomycin Potential against Pathogenic Bacterial Strains via Gold Nano-Formulations: A Nano-Antibiotic Approach.

The remarkable rise of antibiotic resistance among pathogenic bacteria poses a significant threat to human health. Nanoparticles (NPs) have recently emerged as novel strategies for conquering fatal bacterial diseases. Furthermore, antibiotic-functionalized metallic NPs represent a viable nano-platform for combating bacterial resistance. In this study, we present the use of vancomycin-functionalized gold nanoparticles (V-GNPs) to battle pathogenic bacterial strains. A facile one-pot method was adopted to synthesize vancomycin-loaded GNPs in which the reducing properties of vancomycin were exploited to produce V-GNPs from gold ions. UV-Visible spectroscopy verified the production of V-GNPs via the existence of a surface plasmon resonance peak at 524 nm, whereas transmission electron microscopy depicted a size of ~24 nm. Further, dynamic light scattering (DLS) estimated the hydrodynamic diameter as 77 nm. The stability of V-GNPs was investigated using zeta-potential measurements, and the zeta potential of V-GNPs was found to be -18 mV. Fourier transform infrared spectroscopy confirmed the efficient loading of vancomycin onto GNP surfaces; however, the loading efficiency of vancomycin onto V-GNPs was 86.2%. Finally, in vitro antibacterial studies revealed that V-GNPs were much more effective, even at lower concentrations, than pure vancomycin. The observed antibacterial activities of V-GNPs were 1.4-, 1.6-, 1.8-, and 1.6-fold higher against Gram-negative Escherichia coli, Klebsiella oxytoca, and Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus, respectively, compared to pure vancomycin. Collectively, V-GNPs represented a more viable alternative to pure vancomycin, even at a lower antibiotic dose, in conquering pathogenic bacteria.

Gold Nanoparticle-Based Resuscitation of Cefoxitin against Clinical Pathogens: A Nano-Antibiotic Strategy to Overcome Resistance.

Gold nanoparticles have gained popularity as an effective drug delivery vehicle due to their unique features. In fact, antibiotics transported via gold nanoparticles have significantly enhanced their potency in the recent past. The present study used an approach to synthesize gold nanoparticles in one step with the help of cefoxitin antibiotic as a reducing and stabilizing agent. Cefoxitin is a second-generation cephalosporin that loses its potential due to modification in the porins (ompK35 and ompK36) of Gram-negative pathogens. Thus, the present study has developed an idea to revive the potential of cefoxitin against clinical Gram-negative pathogens, i.e., Escherichia coli and Klebsiella pneumoniae, via applying gold nanoparticles as a delivery tool. Prior to antibacterial activity, characterization of cefoxitin-gold nanoparticles was performed via UV-visible spectrophotometry, dynamic light scattering, and electron microscopy. A characteristic UV-visible scan peak for gold nanoparticles was observed at 518 nm, ζ potential was estimated as -23.6 ± 1.6, and TEM estimated the size in the range of 2-12 nm. Moreover, cefoxitin loading efficiency on gold nanoparticles was calculated to be 71.92%. The antibacterial assay revealed that cefoxitin, after loading onto the gold nanoparticles, become potent against cefoxitin-resistant E. coli and K. pneumoniae, and their MIC50 values were estimated as 1.5 µg/mL and 2.5 µg/mL, respectively. Here, gold nanoparticles effectively deliver cefoxitin to the resistant pathogens, and convert it from unresponsive to a potent antibiotic. However, to obtain some convincing conclusions on the human relevance, their fate and toxicity need to be evaluated.

Manganese chloride (MnCl2) induced novel model of Parkinson's disease in adult Zebrafish; Involvement of oxidative stress, neuroinflammation and apoptosis pathway.

Parkinson's disease (PD) is a progressive neurodegenerative disorder imposing a severe health and socioeconomic burden worldwide. Existing pharmacological approaches for developing PD are poorly developed and do not represent all the characteristics of disease pathology. Developing cost-effective, reliable Zebrafish (ZF) model will meet this gap. The present study was conceived to develop a reliable PD model in the ZF using manganese chloride (MnCl2). Here, we report that chronic exposure to 2 mM MnCl2 for 21 days produced non-motor and motor PD-like symptoms in adult ZF. Compared with control fish, MnCl2-treated fish showed reduced locomotory activity, indicating a deficit in motor function. In the light-dark box test, MnCl2-treated fish exhibited anxiety and depression-like behavior. MnCl2-treated fish exhibited a less olfactory preference for amino acids, indicating olfactory dysfunction. These behavioral symptoms were associated with decreased dopamine and increased DOPAC levels. Furthermore, oxidative stress-mediated apoptotic pathway, decreased brain derived neurotropic factor (BDNF) and increased pro-inflammatory cytokines levels were observed upon chronic exposure to MnCl2 in the brain of ZF. Thus, MnCl2-induced PD in ZF can be a cost-effective PD model in the drug discovery process. Moreover, this model could be potentially utilized to investigate the molecular pathways underlying the multifaceted pathophysiology which leads to PD using relatively inexpensive species. MnCl2 being heavy metal may have other side effects in addition to neurotoxicity. Our model recapitulates most of the hallmarks of PD, but not all pathological processes are involved. Future studies are required to recapitulate the complete pathophysiology of PD.