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Targeting microRNAs using nanotechnology in pulmonary diseases

Dua K, Chellappan DK, Singhvi G, de Jesus Andreoli Pinto T, Gupta G, Hansbro PM

Panminerva Med, 2018 Dec;60(4):230-231.
PMID: 30563304 DOI: 10.23736/S0031-0808.18.03459-6
Fulltext Tumor suppressor role of miR-503

Gupta G, Chellappan DK, de Jesus Andreoli Pinto T, Hansbro PM, Bebawy M, Dua K

Panminerva Med, 2018 Mar;60(1):17-24.
PMID: 29164842 DOI: 10.23736/S0031-0808.17.03386-9

MicroRNAs (miRNAs) are non-coding RNAs of around 20-25 nucleotides in length with highly conserved characteristics. They moderate post-transcriptional silencing by precisely combining with 3' untranslated regions (UTRs) of target mRNAs at a complementary site. miR‑503, an associate of the "canonical" miRNA-16 family, is expressed in numerous types of tumors such as breast cancer, prostate cancer, lung cancer, colorectal cancer, hepatocellular carcinoma, glioblastoma and several others. There is convincing evidence to show that miR‑503 functions as a tumor suppressor gene through its effects on target genes that regulate cell proliferation, migration, and invasion in tumor cells. In this current assessment, we discuss the biology and tumor suppressor role of miR‑503 in different cancers and elaborate on its mechanism of action.
Fulltext Advancements in nano drug delivery systems: a challenge for biofilms in respiratory diseases

Dua K, de Jesus Andreoli Pinto T, Chellappan DK, Gupta G, Bebawy M, Hansbro PM

Panminerva Med, 2018 03;60(1):35-36.
PMID: 29370678 DOI: 10.23736/S0031-0808.18.03402-X
Fulltext A clinical update on metformin and lung cancer in diabetic patients

Gupta G, de Jesus Andreoli Pinto T, Chellappan DK, Mishra A, Malipeddi H, Dua K

Panminerva Med, 2018 Jun;60(2):70-75.
PMID: 29370676 DOI: 10.23736/S0031-0808.18.03394-3

Diabetes mellitus (DM) is frequently increased in many countries and become a serious health problem worldwide. Diabetes is associated with dysfunction of different organs such as heart, eyes, blood vessels, nerves, and kidneys. There is a strong connection between diabetes and cancer. Metformin is one of the most commonly prescribed oral antidiabetic medicines and it is suggested as the first-line therapy due to its comparatively safe, inexpensive, effective and well-tolerated. Some of the in vitro and in vivo investigations proved that metformin may have a direct anticancer action by preventing the proliferation of malignant cells and formations of the colony, inducing arrest of cell cycle and apoptosis and suppressing tumor growth. The antiproliferative mechanism of metformin alone or in combination with various chemotherapeutic agents is complex and involves several beneficial roles. In this regard, clinical studies are required to explain these roles. In the coming future, the use of metformin, alone or in combination with current chemotherapy, might be a conventional approach to effectually manage lung cancer. This mini-review provides a critical overview of currently available clinical trials investigating the effects of metformin in lung cancer.
Fulltext Peroxisome proliferator-activated receptor gamma: promising target in glioblastoma

Gupta G, Singhvi G, Chellappan DK, Sharma S, Mishra A, Dahiya R, et al.

Panminerva Med, 2018 Sep;60(3):109-116.
PMID: 30176701 DOI: 10.23736/S0031-0808.18.03462-6

Glioblastoma, also known as glioblastoma multiforme, is the most common and worldwide-spread cancer that begins within the brain. Glioblastomas represent 15% of brain tumors. The most common length of survival following diagnosis is 12 to 14 months with less than 3% to 5% of people surviving longer than five years. Without treatment, survival is typically 3 months. Among all receptors, special attention has been focused on the role of peroxisome proliferator-activated receptors (PPARs) in glioblastoma. PPARs are ligand-activated intracellular transcription factors. The PPAR subfamily consists of three subtypes encoded by distinct genes named PPARα, PPARβ/δ, and PPARγ. PPARγ is the most extensively studied subtype of PPAR. There has been interesting preliminary evidence suggesting that diabetic patients receiving PPARγ agonists, a group of anti-diabetics, thiazolidinedione drugs, have an increased median survival for glioblastoma. In this paper, the recent progresses in understanding the potential mechanism of PPARγ in glioblastoma are summarized.
Fulltext Norfloxacin and metronidazole topical formulations for effective treatment of bacterial infections and burn wounds

Dua K, Malipeddi VR, Madan J, Gupta G, Chakravarthi S, Awasthi R, et al.

Interv Med Appl Sci, 2016 Jun 01;8(2):68-76.
PMID: 28386462 DOI: 10.1556/1646.8.2016.2.4

INTRODUCTION: Our various previous findings have shown the suitability of norfloxacin in the treatment of bacterial infections and burn wounds in alone as well as in combination with Curcuma longa in various topical (ointments, gels, and creams) and transdermal drug delivery systems.
AIMS AND METHODS: Keeping these facts in consideration, we have made an another attempt to prepare semisolid formulations containing 1% w/w of norfloxacin and metronidazole with different bases like Carbopol, polyethylene glycol, and hydroxypropylmethyl cellulose for effective treatment of bacterial infections and burn wounds. The prepared formulations were evaluated for physicochemical parameters, in vitro drug release, antimicrobial activity, and burn wound healing properties.
RESULTS: The prepared formulations were compared with Silver Sulfadiazine cream 1%, USP. Antimicrobial activity of norfloxacin semisolid formulations was found to be equally effective against both aerobic and anaerobic bacteria in comparison to a marketed formulation of Silver Sulfadiazine 1% cream, USP. Based on the burn wound healing property, the prepared norfloxacin semisolid formulation was found to be in good agreement with marketed Silver Sulfadiazine 1% cream, USP.
CONCLUSIONS: These findings suggest formulations containing norfloxacin and metronidazole may also prove as an effective alternative for existing remedies in the treatment of bacterial infections and burn wounds.
Exploring nanoparticular platform in delivery of repurposed drug for Alzheimer's disease: current approaches and future perspectives

Chakraborty S, Vishwas S, Harish V, Gupta G, Paudel KR, Dhanasekaran M, et al.

Expert Opin Drug Deliv, 2024 Dec;21(12):1771-1792.
PMID: 39397403 DOI: 10.1080/17425247.2024.2414768

INTRODUCTION: Alzheimer's disease (AD) stands as significant challenge in realm of neurodegenerative disorder. It is characterized by gradual decline in cognitive function and memory loss. It has already expanded its prevalence to 55 million people worldwide and is expected to rise significantly. Unfortunately, there exists a limited therapeutic option that would mitigate its progression. Repurposing existing drugs and employing nanoparticle as delivery agent presents a potential solution to address the intricate pathology of AD.
AREAS COVERED: In this review, we delve into utilization of nanoparticular platforms to enhance the delivery of repurposed drugs for treatment of AD. Firstly, the review begins with the elucidation of intricate pathology underpinning AD, subsequently followed by rationale behind drug repurposing in AD. Covered are explorations of nanoparticle-based repurposing of drugs in AD, highlighting their clinical implication. Further, the associated challenges and probable future perspective are delineated.
EXPERT OPINION: The article has highlighted that extensive research has been carried out on the delivery of repurposed nanomedicines against AD. However, there is a need for advanced and long-term research including clinical trials required to shed light upon their safety and toxicity profile. Furthermore, their scalability in pharmaceutical set-up should also be validated.
Hybrid molecules based on 1,3,5-triazine as potential therapeutics: A focused review

Prasher P, Sharma M, Aljabali AAA, Gupta G, Negi P, Kapoor DN, et al.

Drug Dev Res, 2020 11;81(7):837-858.
PMID: 32579723 DOI: 10.1002/ddr.21704

Majority of the representative drugs customarily interact with multiple targets manifesting unintended side effects. In addition, drug resistance and over expression of the cellular efflux-pumps render certain classes of drugs ineffective. With only a few innovative formulations in development, it is necessary to identify pharmacophores and novel strategies for creating new drugs. The conjugation of dissimilar pharmacophoric moieties to design hybrid molecules with an attractive therapeutic profile is an emerging paradigm in the contemporary drug development regime. The recent decade witnessed the remarkable biological potential of 1,3,5-triazine framework in the development of various chemotherapeutics. The appending of the 1,3,5-triazine nucleus to biologically relevant moieties has delivered exciting results. The present review focuses on 1,3,5-triazine based hybrid molecules in the development of pharmaceuticals.
Berberine-loaded engineered nanoparticles attenuate TGF-β-induced remodelling in human bronchial epithelial cells

De Rubis G, Paudel KR, Liu G, Agarwal V, MacLoughlin R, de Jesus Andreoli Pinto T, et al.

Toxicol In Vitro, 2023 Oct;92:105660.
PMID: 37591407 DOI: 10.1016/j.tiv.2023.105660

Airway remodelling occurs in chronic respiratory diseases (CRDs) such as asthma and chronic obstructive pulmonary disease (COPD). It is characterized by aberrant activation of epithelial reparation, excessive extracellular matrix (ECM) deposition, epithelial-to-mesenchymal transition (EMT), and airway obstruction. The master regulator is Transforming Growth Factor-β (TGF-β), which activates tissue repair, release of growth factors, EMT, increased cell proliferation, and reduced nitric oxide (NO) secretion. Due to its fundamental role in remodelling, TGF-β is an emerging target in the treatment of CRDs. Berberine is a benzylisoquinoline alkaloid with antioxidant, anti-inflammatory, and anti-fibrotic activities whose clinical application is hampered by poor permeability. To overcome these limitations, in this study, berberine was encapsulated in monoolein-based liquid crystalline nanoparticles (BM-LCNs). The potential of BM-LCNs in inhibiting TGF-β-induced remodelling features in human bronchial epithelial cells (BEAS-2B) was tested. BM-LCNs significantly inhibited TGF-β-induced migration, reducing the levels of proteins upregulated by TGF-β including endoglin, thrombospondin-1, basic fibroblast growth factor, vascular-endothelial growth factor, and myeloperoxidase, and increasing the levels of cystatin C, a protein whose expression was downregulated by TGF-β. Furthermore, BM-LCNs restored baseline NO levels downregulated by TGF-β. The results prove the in vitro therapeutic efficacy of BM-LCNs in counteracting TGF-β-induced remodelling features. This study supports the suitability of berberine-loaded drug delivery systems to counteract airway remodelling, with potential application as a treatment strategy against CRDs.