Magnetic nanoflowers: a hybrid platform for enzyme immobilization.

The use of organic-inorganic hybrid nanoflowers as a support material for enzyme immobilization has gained significant attention in recent years due to their high stability, ease of preparation, and enhanced catalytic activity. However, a major challenge in utilizing these hybrid nanoflowers for enzyme immobilization is the difficulty in handling and separating them due to their low density and high dispersion. To address this issue, magnetic nanoflowers have emerged as a promising alternative enzyme immobilization platform due to their easy separation, structural stability, and ability to enhance catalytic efficiency. This review focuses on different methods for designing magnetic nanoflowers, as well as future research directions. Additionally, it provides examples of enzymes immobilized in the form of magnetic nanoflowers and their applications in environmental remediation, biosensors, and food industries. Finally, the review discusses possible ways to improve the material for enhanced catalytic activity, structural stability, and scalability.

Magnetic nanoflowers can be used as a novel platform for enzyme immobilization.There are three different approaches to the synthesis of efficient magnetic nanoflower.The magnetic nanoflowers provides excellent stability and good reusability of enzymes.The hybrid biocatalyst was applied in biotransformation, environmental, and food applications.The challenges and their remedies of hybrid biocatalyst have been discussed.

Exploring Amodiaquine's Repurposing Potential in Breast Cancer Treatment-Assessment of In-Vitro Efficacy & Mechanism of Action.

Due to the heterogeneity of breast cancer, current available treatment options are moderately effective at best. Hence, it is highly recommended to comprehend different subtypes, understand pathogenic mechanisms involved, and develop treatment modalities. The repurposing of an old FDA approved anti-malarial drug, amodiaquine (AQ) presents an outstanding opportunity to explore its efficacy in treating majority of breast cancer subtypes. Cytotoxicity, scratch assay, vasculogenic mimicry study, and clonogenic assay were employed to determine AQ's ability to inhibit cell viability, cell migration, vascular formation, and colony growth. 3D Spheroid cell culture studies were performed to identify tumor growth inhibition potential of AQ in MCF-7 and MDAMB-231 cell lines. Apoptosis assays, cell cycle analysis, RT-qPCR assays, and Western blot studies were performed to determine AQ's ability to induce apoptosis, cell cycle changes, gene expression changes, and induction of autophagy marker proteins. The results from in-vitro studies confirmed the potential of AQ as an anti-cancer drug. In different breast cancer cell lines tested, AQ significantly induces cytotoxicity, inhibit colony formation, inhibit cell migration, reduces 3D spheroid volume, induces apoptosis, blocks cell cycle progression, inhibit expression of cancer related genes, and induces LC3BII protein to inhibit autophagy. Our results demonstrate that amodiaquine is a promising drug to repurpose for breast cancer treatment, which needs numerous efforts from further studies.

Development of gelatin methacrylate (GelMa) hydrogels for versatile intracavitary applications.

Applicability of hydrogels as drug delivery systems is on the rise due to their highly tunable degree of polymeric crosslinking to attain varying rates of payload release. Sustaining the release of therapeutic payloads at certain physiological sites has been the need of the hour to treat disorders such as peritoneal or pleural malignancies. These disorders can be targeted via intracavitary administration of hydrogels, providing localized therapy. In this study, a gelatin methacrylate (GelMa) hydrogel with tunable physicochemical traits is developed and characterized. A hydrogel-based depot system was curated using GelMa as backbone, a photo-initiator (lithium phenyl-2,4,6-trimethylbenzoylphosphinate) and a chemical crosslinker (N,N-methylenebisacrylamide). Hydrogels were optimized using a 23 factorial design, by testing for their gelling time, injectability, viscosity change, elasticity, bio-adhesion, swelling-index, in vitro degradation, in vitro release, and biocompatibility. Gelling time for hydrogel formulations was found to be <60 seconds with gelling being achieved in as fast as 24 seconds. Bio-adhesion studies revealed that formulations with higher concentrations of both crosslinkers had more adhesion to guinea pig lung tissues. Hydrogels with higher swelling showcased a more sustained release. Biocompatibility studies for hydrogel formulations was done by evaluating formulation performance in MTT, live/dead, and apoptosis assays performed using non-malignant Human embryonic kidney cells (HEK-293). The optimized hydrogel formulations were biocompatible, yielding >90% cellular viability over 72 hours. This delivery system prototype may be used to deliver potent chemotherapeutics locally, reducing off target effects and improving therapeutic benefits.

Repurposing clofazimine for malignant pleural mesothelioma treatment - In-vitro assessment of efficacy and mechanism of action.

AIMS: Malignant pleural mesothelioma (MPM) is a rare cancer of lungs' pleural cavity, with minimally effective therapies available. Thus, there exists a necessity for drug repurposing which is an attractive strategy for drug development in MPM. Repurposing of an old FDA-approved anti-leprotic drug, Clofazimine (CFZ), presents an outstanding opportunity to explore its efficacy in treating MPM. MAIN METHODS: Cytotoxicity, scratch assay, and clonogenic assays were employed to determine CFZ's ability to inhibit cell viability, cell migration, and colony growth. 3D Spheroid cell culture studies were performed to identify tumor growth inhibition potential of CFZ in MSTO-211H cell line. Gene expression analysis was performed using RT-qPCR assays to determine the CFZ's effect of key genes. Western blot studies were performed to determine CFZ's ability to induce apoptosis its effect to induce autophagy marker. KEY FINDINGS: CFZ showed significant cytotoxicity against both immortalized and primary patient-derived cell lines with IC50 values ranging from 3.4 µM (MSTO-211H) to 7.1 µM (HAY). CFZ significantly impaired MPM cell cloning efficiency, migration, and tumor spheroid formation. 3D Spheroid model showed that CFZ resulted in reduction in spheroid volume. RT-qPCR data showed downregulation of genes ß-catenin, BCL-9, and PRDX1; and upregulation of apoptosis markers such as PARP, Cleaved caspase 3, and AXIN2. Additionally, immunoblot analysis showed that CFZ down-regulates the expression of ß-catenin (apoptosis induction) and up-regulates p62, LC3B protein II (autophagy inhibition). SIGNIFICANCE: It can be concluded that CFZ could be a promising molecule to repurpose for MPM treatment which needs numerous efforts from further studies.

Repurposing therapeutics for malignant pleural mesothelioma (MPM) - Updates on clinical translations and future outlook.

INTRODUCTION: Malignant pleural mesothelioma (MPM) is a rare malignancy affecting the mesothelial cells in the pleural lining surrounding the lungs. First approved chemotherapy against MPM was a platinum/antifolate (cisplatin/pemetrexed) (2003). Since then, no USFDA approvals have gone through for small molecules as these molecules have not been proven to be therapeutically able in later stages of clinical studies. An alternative to conventional chemotherapy can be utilization of monoclonal antibodies, which are proven to improve patient survival significantly as compared to conventional chemotherapy (Nivolumab + Ipilimumab, 2020). AREA COVERED: Drug repurposing has been instrumental in drug discovery for rare diseases such as MPM and multiple repositioned small molecule therapies and immunotherapies are currently being tested for its applicability in MPM management. This article summarizes essential breakthroughs along the pre-clinical and clinical developmental stages of small molecules and monoclonal antibodies for MPM management. EXPERT OPINION: For rare diseases such as malignant pleural mesothelioma, a drug repurposing strategy can be adapted as it eases the financial burden on pharmaceutical companies along with fast-tracking development. With the rise of multiple small molecule repurposed therapies and innovations in localized treatment, MPM therapeutics are bound to be more effective in this decade.

Pulmonary delivery of osimertinib liposomes for non-small cell lung cancer treatment: formulation development and in vitro evaluation.

Osimertinib (OB) is a third-generation irreversible tyrosine kinase inhibitor targeting the epidermal growth factor receptor (EGFR), overexpressed in non-small cell lung cancer. Systemic administration of drug often results in poor drug levels at the primary tumor in the lungs and is associated with systemic side effects. In this study, we developed inhalable OB liposomes that can locally accumulate at the tumor site thereby limiting systemic toxicity. OB was loaded into liposomes via active and passive loading methods. The OB active liposomes achieved a higher encapsulation (78%) compared to passive liposomes (25%). The liposomes (passive and active) exhibited excellent aerosolization performance with an aerodynamic diameter of 4 µm and fine particle fraction of 82%. In H1975 cells, OB active and passive liposomes reduced IC50 by 2.2 and 1.2-fold, respectively, compared to free drug. As the OB active liposomes demonstrated higher cytotoxicity compared to OB passive liposomes, they were further investigated for in vitro anti-cancer activity. The OB active liposomes inhibited tumor cell migration and colonization as determined by the scratch assay and clonogenic assay, respectively. Furthermore, the 3D spheroid studies showed that the liposomes were successful in inhibiting tumor growth. These results highlight the potential of OB liposomes to suppress lung cancer. Owing to these attributes, the inhalable OB liposomes can potentially promote better therapeutic outcomes with limited systemic toxicity.

Development and characterization of inhalable transferrin functionalized amodiaquine nanoparticles - Efficacy in Non-Small Cell Lung Cancer (NSCLC) treatment.

New drug discovery and development processes encounter significant challenges including requirement of huge investments and lengthy time frames especially in cancer research field. Repurposing of old drugs against cancer provides a possible alternative while associated scale-up complexities with production of nanoparticles at industrial scale could be overcome by using a scalable nanoparticle technique. We previously described use of polymeric nanoparticles for inhaled delivery of amodiaquine (AQ) for non-small cell lung cancer (NSCLC) treatment. In this study, targeting potential of transferrin ligand conjugated inhalable AQ-loaded nanoparticles (Tf-AMQ NPs) was investigated against NSCLC. Tf-AMQ NP (liquid formulation) demonstrated an aerodynamic diameter of 4.4 ± 0.1 µm and fine particle fraction of 83.2 ± 3.0%, representing AQ deposition in the respirable region of airways. Cytotoxicity studies in NSCLC cell line with overexpressed transferrin receptors shown significant reduction in IC50 values with Tf-decorated AQ-loaded nanoparticles compared to AQ or non-targeted NPs, along with significant apoptosis induction (caspase assay) and reduced % colony growth in A549 and H1299 cells with Tf-AMQ NP. Furthermore, 3D spheroid studies (~7-fold reduction in spheroid volume compared to AMQ NPs) explained efficiency of conjugated nanoparticles in penetrating tumor core, and growth inhibition. AQ's autophagy inhibition ability significantly increased with nanoparticle encapsulation and transferrin conjugation. In conclusion, amodiaquine can be an assuring candidate for repurposing to consider for NSCLC treatment while delivering inhalable transferrin conjugated nanoparticles developed using a scalable HPH process to the target site, thus reducing the dose, side effects.

Nano-synergistic combination of Erlotinib and Quinacrine for non-small cell lung cancer (NSCLC) therapeutics - Evaluation in biologically relevant in-vitro models.

Non-small cell lung cancer (NSCLC), pre-dominant subtype of lung cancer, is a global disorder affecting millions worldwide. One of the early treatments for NSCLC was use of a first-generation tyrosine kinase inhibitor, Erlotinib (Erlo). However, chronic exposure to Erlo led to development of acquired drug resistance (ADR) in NSCLC, limiting the clinical use of Erlo. A potential approach to overcome development of ADR is a multi-drug therapy. It has been previously reported that Erlo and Quinacrine (QA), an anti-malarial drug, can work synergistically to inhibit tumor progression in NSCLC. However, the combination failed at clinical stages, citing lack of efficacy. In this study, an effort has been made to improve the efficacy of Erlo-QA combination via development of nanoformulations, known to enhance therapeutic efficacy of potent chemotherapies. Synergy between Erlo and QA was measured via estimating the combination indices (CI). It was seen that established combination of nanoformulations (CI: 0.25) had better synergy than plain drug solutions (CI: 0.85) in combination. Following extensive in-vitro testing, data were simulated in biologically relevant 3D tumor models. Two tumor models were developed for extensive in-vitro testing, 3D-Spheroids grown in ultra-low attachment culture plates for efficacy evaluation and a 5D-spheroid model in 5D-sphericalplate with capability of growing 750 spheroids/well for protein expression analysis. Extensive studies on these models revealed that combination of Erlo and QA nanoformulations overall had a better effect in terms of synergy enhancement as compared to plain drug combination. Further, effect of combinatorial therapy on molecular markers was evaluated on 5D-Sphericalplate leading to similar effects on synergy enhancement. Results from present study suggests that combination of nanoformulations can improve the synergy between Erlo and QA while reducing the overall therapeutic dose.

Afatinib-loaded inhalable PLGA nanoparticles for localized therapy of non-small cell lung cancer (NSCLC)-development and in-vitro efficacy.

Afatinib (AFA) is a potent aniline-quinazoline derivative, approved by the Food and Drug Administration (FDA) in 2013, as a first-line treatment for metastatic non-small cell lung cancer (NSCLC). However, its clinical application is highly limited by its poor solubility, and consequently low bioavailability. We hypothesize that loading of AFA into biodegradable PLGA nanoparticles for localized inhalational drug delivery will be instrumental in improving therapeutic outcomes in NSCLC patients. Formulated AFA nanoparticles (AFA-NP) were evaluated for physicochemical properties (particle size: 180.2 ± 15.6 nm, zeta potential: - 23.1 ± 0.2 mV, % entrapment efficiency: 34.4 ± 2.3%), formulation stability, in-vitro aerosol deposition behavior, and anticancer efficacy. Stability studies revealed the physicochemical stability of AFA-NP. Moreover, AFA-NP exhibited excellent inhalable properties (mass median aerodynamic diameter (MMAD): 4.7 ± 0.1 µm; fine particle fraction (FPF): 77.8 ± 4.3%), indicating efficient particle deposition in deep lung regions. With respect to in-vitro drug release, AFA-NP showed sustained drug release with cumulative release of 56.8 ± 6.4% after 48 h. Cytotoxic studies revealed that encapsulation of AFA into PLGA nanoparticles significantly enhanced its cytotoxic potential in KRAS-mutated NSCLC cell lines (A549, H460). Cellular uptake studies revealed enhanced internalization of coumarin-loaded nanoparticles compared to plain coumarin in A549. In addition, 3D tumor spheroid studies demonstrated superior efficacy of AFA-NP in tumor penetration and growth inhibition. To conclude, we have established in-vitro efficacy of afatinib-loaded PLGA nanoparticles as inhalable NSCLC therapy, which will be of great significance when designing preclinical and clinical studies. Graphical abstract.

Repurposing Quinacrine for Treatment of Malignant Mesothelioma: In-Vitro Therapeutic and Mechanistic Evaluation.

Malignant mesothelioma (MM) is a rare type of cancer primarily affecting mesothelial cells lining the pleural cavity. In this study, we propose to repurpose quinacrine (QA), a widely approved anti-malarial drug, for Malignant Pleural Mesothelioma (MPM) treatment. QA demonstrates high degree of cytotoxicity against both immortalized and primary patient-derived cell lines with sub-micromolar 50% inhibitory concentration (IC50) values ranging from 1.2 µM (H2452) to 5.03 µM (H28). Further, QA also inhibited cellular migration and colony formation in MPM cells, demonstrated using scratch and clonogenic assays, respectively. A 3D-spheroid cell culture experiment was performed to mimic in-vivo tumor conditions, and QA was reported to be highly effective in this simulated cellular model. Anti-angiogenic properties were also discovered for QA. Autophagy inhibition assay was performed, and results revealed that QA successfully inhibited autophagy process in MPM cells, which has been cited to be one of the survival pathways for MPM. Annexin V real-time apoptosis study revealed significant apoptotic induction in MPM cells following QA treatment. Western blots confirmed inhibition of autophagy and induction of apoptosis. These studies highlight anti-mesothelioma efficacy of QA at low doses, which can be instrumental in developing it as a stand-alone treatment strategy for MPM.

The preparation of lipid-based drug delivery system using melt extrusion.

Melt extrusion of lipids is versatile with high applicability in the pharmaceutical industry. The formulations prepared can be easily customized depending on the requirements, and have the potential to open a window on personalized medicine.

Development of pharmaceutically scalable inhaled anti-cancer nanotherapy - Repurposing amodiaquine for non-small cell lung cancer (NSCLC).

New drug and dosage form development faces significant challenges, especially in oncology, due to longer development cycle and associated scale-up complexities. Repurposing of existing drugs with potential anti-cancer activity into new therapeutic regimens provides a feasible alternative. In this project, amodiaquine (AQ), an anti-malarial drug, has been explored for its anti-cancer efficacy through formulating inhalable nanoparticulate systems using high-pressure homogenization (HPH) with scale-up feasibility and high reproducibility. A 32 multifactorial design was employed to better understand critical processes (probe homogenization speed while formulating coarse emulsion) and formulation parameters (concentration of cationic polymer in external aqueous phase) so as to ensure product quality with improved anticancer efficacy in non-small cell lung cancer (NSCLC). Optimized AQ loaded nanoparticles (AQ NP) were evaluated for physicochemical properties, stability profile, in-vitro aerosol deposition behavior, cytotoxic potential against NSCLC cells in-vitro and in 3D simulated tumor spheroid model. The highest probe homogenization speed (25,000 rpm) resulted in lower particle size. Incorporation of cationic polymer, polyethylenimine (0.5% w/v) resulted in high drug loading efficiencies at optimal drug quantity of 5 mg. Formulated nanoparticles (liquid state) exhibited an aerodynamic diameter of 4.7 ± 0.1 µm and fine particle fraction of 81.0 ± 9.1%, indicating drug deposition in the respirable airways. Cytotoxicity studies in different NSCLC cell lines revealed significant reduction in IC50 values with AQ-loaded nanoparticles compared to plain drug, along with significant cell migration inhibition (scratch assay) and reduced % colony growth (clonogenic assay) in A549 cells with AQ NP. Moreover, 3D simulated spheroid studies revealed efficacy of nanoparticles in penetration to tumor core, and growth inhibition. AQ's autophagy inhibition ability significantly increased (increased LC3B-II levels) with nanoparticle encapsulation, along with moderate improvement in apoptosis induction (Caspase-3 levels). No impact was observed on HUVEC angiogenesis suggesting alternative anticancer mechanisms. To conclude, amodiaquine can be a promising candidate for repurposing to treat NSCLC while delivering inhalable nanoparticles developed using a scalable HPH process. Despite the involvement of complex parameters, application of DoE has simplified the process of product and process optimization.

Inhalable resveratrol-cyclodextrin complex loaded biodegradable nanoparticles for enhanced efficacy against non-small cell lung cancer.

Resveratrol (RES), a natural polyphenol in fruits, has shown promising anti-cancer properties. Due to its relative low toxicity which limits the adverse effects observed for conventional chemotherapeutics, RES has been proposed as an alternative. However, the therapeutic applications of RES have been limited due to low water solubility, as well as chemical and physical instability. This study investigated enhancing the anti-cancer activity of RES against non-small-cell-lung-cancer (NSCLC) by complexing with sulfobutylether-ß-cyclodextrin (CD-RES) and loading onto polymeric nanoparticles (NPs). The physicochemical properties of the CD-RES NPs were then characterized. The CD-RES inclusion complex increased the water solubility of RES by ~66-fold. CD-RES NPs demonstrated very good aerosolization potential with a mass median aerodynamic diameter of 2.20 µm. Cell-based studies demonstrated improved therapeutic efficacy of CD-RES NPs compared to RES. This included enhanced cellular uptake, cytotoxicity, and apoptosis, while retaining antioxidant activity. The 3D spheroid study indicated an intensified anti-cancer effect of CD-RES NPs. Altogether, these findings marked CD-RES NPs as a potential inhalable delivery system of RES for the treatment NSCLC.

Nanotechnology Based Repositioning of an Anti-Viral Drug for Non-Small Cell Lung Cancer (NSCLC).

PURPOSE: Nelfinavir (NFV), a FDA approved antiretroviral drug, has been reported to exhibit cancer cells growth inhibition and increased apoptosis. However, it requires a higher dose leading to toxicity, thus limiting its potential clinical translation. We aim to develop biodegradable (poly (lactic-co-glycolic acid)) PLGA nanoparticles of nelfinavir and determine their efficacy to treat non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: HIV protease inhibitor, NFV, was loaded into PLGA nanoparticles by double emulsion/solvent evaporation method; and nanoparticles were characterized for physicochemical characteristics including morphology and intracellular uptake. Their anti-cancer efficacy in NSCLC was assessed by in vitro assays including cytotoxicity, cellular migration, colony formation; and 3D spheroid culture mimicking in-vivo tumor microenvironment. Studies were also conducted to elucidate effects on molecular pathways including apoptosis, autophagy, and endoplasmic stress. RESULTS: NFV loaded PLGA nanoparticles (NPs) were found to have particle size: 191.1 ± 10.0 nm, zeta potential: -24.3 ± 0.9 mV, % drug loading: 2.5 ± 0.0%; and entrapment efficiency (EE): 30.1 ± 0.5%. NFV NP inhibited proliferation of NSCLC cells compared to NFV and exhibited significant IC50 reduction. From the caspase-dependent apoptosis assays and western blot studies (upregulation of ATF3), it was revealed that NFV NP significantly induced ER stress marker ATF3, cleaved PARP and further caused autophagy inhibition (LC3BII upregulation) leading to increased cellular death. In addition, NFV NP were found to be more efficacious in penetrating solid tumors in ex-vivo studies compared to plain NFV. CONCLUSIONS: Nelfinavir, a lead HIV protease inhibitor can be repositioned as a NSCLC therapeutic through nanoparticulate delivery. Given its ability to induce apoptosis and efficient tumor penetration capability, NFV loaded PLGA nanoparticulate systems provide a promising delivery system in NSCLC treatment.

Sorafenib Loaded Inhalable Polymeric Nanocarriers against Non-Small Cell Lung Cancer.

PURPOSE: This exploration is aimed at developing sorafenib (SF)-loaded cationically-modified polymeric nanoparticles (NPs) as inhalable carriers for improving the therapeutic efficacy of SF against non-small cell lung cancer (NSCLC). METHODS: The NPs were prepared using a solvent evaporation technique while incorporating cationic agents. The optimized NPs were characterized by various physicochemical parameters and evaluated for their aerosolization properties. Several in-vitro evaluation studies were performed to determine the efficacy of our delivery carriers against NSCLC cells. RESULTS: Optimized nanoparticles exhibited an entrapment efficiency of ~40%, <200 nm particle size and a narrow poly-dispersity index. Cationically-modified nanoparticles exhibited enhanced cellular internalization and cytotoxicity (~5-fold IC50 reduction vs SF) in various lung cancer cell types. The inhalable nanoparticles displayed efficient aerodynamic properties (MMAD ~ 4 µM and FPF >80%). In-vitro evaluation also resulted in a superior ability to inhibit cancer metastasis. 3D-tumor simulation studies further established the anti-cancer efficacy of NPs as compared to just SF. CONCLUSION: The localized delivery of SF-loaded nanoparticles resulted in improved anti-tumor activity as compared to SF alone. Therefore, this strategy displays great potential as a novel treatment approach against certain lung cancers.

Systematic Development and Optimization of Inhalable Pirfenidone Liposomes for Non-Small Cell Lung Cancer Treatment.

Non-small cell lung cancer (NSCLC) is a global disorder, treatment options for which remain limited with resistance development by cancer cells and off-target events being major roadblocks for current therapies. The discovery of new drug molecules remains time-consuming, expensive, and prone to failure in safety/efficacy studies. Drug repurposing (i.e., investigating FDA-approved drug molecules for use against new indications) provides an opportunity to shorten the drug development cycle. In this project, we propose to repurpose pirfenidone (PFD), an anti-fibrotic drug, for NSCLC treatment by encapsulation in a cationic liposomal carrier. Liposomal formulations were optimized and evaluated for their physicochemical properties, in-vitro aerosol deposition behavior, cellular internalization capability, and therapeutic potential against NSCLC cell lines in-vitro and ex-vivo. Anti-cancer activity of PFD-loaded liposomes and molecular mechanistic efficacy was determined through colony formation (1.5- to 2-fold reduction in colony growth compared to PFD treatment in H4006, A549 cell lines, respectively), cell migration, apoptosis and angiogenesis assays. Ex-vivo studies using 3D tumor spheroid models revealed superior efficacy of PFD-loaded liposomes against NSCLC, as compared to plain PFD. Hence, the potential of inhalable liposome-loaded pirfenidone in NSCLC treatment has been established in-vitro and ex-vivo, where further studies are required to determine their efficacy through in vivo preclinical studies followed by clinical studies.

Development of inhalable quinacrine loaded bovine serum albumin modified cationic nanoparticles: Repurposing quinacrine for lung cancer therapeutics.

Drug repurposing is on the rise as an atypical strategy for discovery of new molecules, involving use of pre-existing molecules for a different therapeutic application than the approved indication. Using this strategy, the current study aims to leverage effects of quinacrine (QA), a well-known anti-malarial drug, for treatment of non-small cell lung cancer (NSCLC). For respiratory diseases, designing a QA loaded inhalable delivery system has multiple advantages over invasive delivery. QA-loaded nanoparticles (NPs) were thus prepared using polyethyleneimine (PEI) as a cationic stabilizer. While the use of PEI provided cationic charge on the particles, it also mediated a burst release of QA and demonstrated potential particle toxicity. These concerns were circumvented by coating nanoparticles with bovine serum albumin (BSA), which retained the cationic charge, reduced NP toxicity and modulated QA release. Prepared nanoparticles were characterized for physicochemical properties along with their aerosolization potential. Therapeutic efficacy of the formulations was tested in different NSCLC cells. Mechanism of higher anti-proliferation was evaluated by studying cell cycle profile, apoptosis and molecular markers involved in the progression of lung cancer. BSA coated QA nanoparticles demonstrated good aerosolization potential with a mass median aerodynamic diameter of significantly less than 5 µm. Nanoparticles also demonstrated improved therapeutic efficacy against NSCLC cells in terms of low IC50 values, cell cycle arrest at G2/M phase and autophagy inhibition leading to increased apoptosis. BSA coated QA NPs also demonstrated enhanced therapeutic efficacy in a 3D cell culture model. The present study thus lays solid groundwork for pre-clinical and eventual clinical studies as a standalone therapy and in combination with existing chemotherapeutics.

Metformin-Encapsulated Liposome Delivery System: An Effective Treatment Approach against Breast Cancer.

This study aimed at developing metformin hydrochloride (Met) encapsulated liposomal vesicles for enhanced therapeutic outcomes at reduced doses against breast cancer. Liposomal Met was prepared using thin-film hydration through various loading methods; passive loading, active loading, and drug-loaded lipid film. The drug-loaded film method exhibited maximum entrapment efficiency (~65%) as compared to active loading (~25%) and passive loading (~5%) prepared Met-loaded liposomes. The therapeutic efficacy of these optimized liposomes was evaluated for cellular uptake, cytotoxicity, inhibition of metastatic activity, and apoptosis-inducing activity. Results demonstrated significantly superior activity of positively charged liposomes resulting in reduced IC50 values, minimal cell migration activity, reduced colony formation, and profound apoptosis-induced activity in breast cancer cells as compared to Met. The anti-tumor activity was investigated using a clinically relevant in vitro tumor simulation model, which confirmed enhanced anti-tumorigenic property of liposomal Met over Met itself. To the authors' knowledge, this is the first report of Met-loaded liposomes for improving the efficacy and therapeutic effect of Met against breast cancer. With the results obtained, it can be speculated that liposomal encapsulation of metformin offers a potentially promising and convenient approach for enhanced efficacy and bioavailability in breast cancer treatment.

Drug repurposing: a promising tool to accelerate the drug discovery process.

Traditional drug discovery and development involves several stages for the discovery of a new drug and to obtain marketing approval. It is necessary to discover new strategies for reducing the drug discovery time frame. Today, drug repurposing has gained importance in identifying new therapeutic uses for already-available drugs. Typically, repurposing can be achieved serendipitously (unintentional fortunate observations) or through systematic approaches. Numerous strategies to discover new indications for FDA-approved drugs are discussed in this article. Drug repurposing has therefore become a productive approach for drug discovery because it provides a novel way to explore old drugs for new use but encounters several challenges. Some examples of different approaches are reviewed here.