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Treatment avenues for age-related macular degeneration: Breakthroughs and bottlenecks

Kumbhar P, Kolekar K, Vishwas S, Shetti P, Kumbar V, Andreoli Pinto TJ, et al.

Ageing Res Rev, 2024 Jul;98:102322.
PMID: 38723753 DOI: 10.1016/j.arr.2024.102322

Age-related macular degeneration (AMD) is a significant factor contributing to serious vision loss in adults above 50. The presence of posterior segment barriers serves as chief roadblocks in the delivery of drugs to treat AMD. The conventional treatment strategies use is limited due to its off-targeted distribution in the eye, shorter drug residence, poor penetration and bioavailability, fatal side effects, etc. The above-mentioned downside necessitates drug delivery using some cutting-edge technology including diverse nanoparticulate systems and microneedles (MNs) which provide the best therapeutic delivery alternative to treat AMD efficiently. Furthermore, cutting-edge treatment modalities including gene therapy and stem cell therapy can control AMD effectively by reducing the boundaries of conventional therapies with a single dose. This review discusses AMD overview, conventional therapies for AMD and their restrictions, repurposed therapeutics and their anti-AMD activity through different mechanisms, and diverse barriers in drug delivery for AMD. Various nanoparticulate-based approaches including polymeric NPs, lipidic NPs, exosomes, active targeted NPs, stimuli-sensitive NPs, cell membrane-coated NPs, inorganic NPs, and MNs are explained. Gene therapy, stem cell therapy, and therapies in clinical trials to treat AMD are also discussed. Further, bottlenecks of cutting-edge (nanoparticulate) technology-based drug delivery are briefed. In a nutshell, cutting-edge technology-based therapies can be an effective way to treat AMD.
Bridging gap in treatment of polycystic ovarian syndrome through drug repurposing: what we achieved and where we are?

Kumbhar PS, Chavan R, Darekar S, Kolekar K, Sequeira A, Vishwas S, et al.

Naunyn Schmiedebergs Arch Pharmacol, 2024 Nov 09.
PMID: 39520555 DOI: 10.1007/s00210-024-03578-7

Polycystic ovarian syndrome (PCOS) is one of the chief causes of infertility in women of reproductive age. Several drugs belonging to the oral contraceptive class have been approved for the treatment of PCOS. Nonetheless, the capability to target only a few symptoms of PCOS and fatal side effects are key hurdles to their use. Therefore, repurposing existing drugs can be promising in managing PCOS efficiently. Drugs from different pharmacological classes like antidiabetics (metformin, rosiglitazone, pioglitazone, and semaglutide), statins (simvastatin and atorvastatin), antiandrogen drugs (finasteride and flutamide), etc. demonstrated significant potential in managing PCOS. The present review offers a comprehensive overview of all the medications examined as potential repurposed options for the efficient treatment of PCOS. The pathogenesis of PCOS, existing therapies for PCOS and their challenges, drug repurposing and its significance is also explained. The small-molecular drugs from various pharmacological classes and different phytoceuticals repurposed against PCOS are discussed along with their anti-PCOS activity mechanisms. Moreover, novel drug targets responsible for PCOS and opportunities for drug repurposing are briefed. The repurposed drugs in clinical trials for PCOS and drug repurposing challenges are discussed. Thus, drug repurposing can serve as a potential way to effectively treat PCOS, reducing the extent of infertility and improving the quality of life of women.
Unravelling the success of transferosomes against skin cancer: Journey so far and road ahead

Kumbhar PS, Kamble V, Vishwas S, Kumbhar P, Kolekar K, Gupta G, et al.

Drug Deliv Transl Res, 2024 Sep;14(9):2325-2344.
PMID: 38758498 DOI: 10.1007/s13346-024-01607-9

Skin cancer remains one of the most prominent types of cancer. Melanoma and non-melanoma skin cancer are commonly found together, with melanoma being the more deadly type. Skin cancer can be effectively treated with chemotherapy, which mostly uses small molecular medicines, phytoceuticals, and biomacromolecules. Topical delivery of these therapeutics is a non-invasive way that might be useful in effectively managing skin cancer. Different skin barriers, however, presented a major obstacle to topical cargo administration. Transferosomes have demonstrated significant potential in topical delivery by improving cargo penetration through the circumvention of diverse skin barriers. Additionally, the transferosome-based gel can prolong the residence of drug on the skin, lowering the frequency of doses and their associated side effects. However, the choice of appropriate transferosome compositions, such as phospholipids and edge activators, and fabrication technique are crucial for achieving improved entrapment efficiency, penetration, and regulated particle size. The present review discusses skin cancer overview, current treatment strategies for skin cancer and their drawbacks. Topical drug delivery against skin cancer is also covered, along with the difficulties associated with it and the importance of transferosomes in avoiding these difficulties. Additionally, a summary of transferosome compositions and fabrication methods is provided. Furthermore, topical delivery of small molecular drugs, phytoceuticals, and biomacromolecules using transferosomes and transferosomes-based gel in treating skin cancer is discussed. Thus, transferosomes can be a significant option in the topical delivery of drugs to manage skin cancer efficiently.
Non-coding RNAs as key regulators of Gasdermin-D mediated pyroptosis in cancer therapy

Gupta G, Afzal M, Moglad E, Ali H, Singh TG, Kumbhar P, et al.

Pathol Res Pract, 2024 Sep;261:155490.
PMID: 39126977 DOI: 10.1016/j.prp.2024.155490

Pyroptosis is an inflammatory programed cell death process that plays a crucial role in cancer therapeutic, while Gasdermin-D is a critical effector protein for pyroptosis execution. This review discusses the intricate interactions between Gasdermin-D and some non-coding RNAs (lncRNA, miRNA, siRNA) and their potential application in the regulation of pyroptosis as an anticancer therapy. Correspondingly, these ncRNAs significantly implicate in Gasdermin-D expression and function regarding the pyroptosis pathway. Functioning as competing endogenous RNAs (ceRNAs), these ncRNAs might regulate Gasdermin-D at the molecular level, underlying fatal cell death caused by cancer and tumor propagation. Therefore, these interactions appeal to therapeutics, offering new avenues for cancer treatment. It address this research gap by discussing the possible roles of ncRNAs as mediators of gasdermin-D regulation. It suggest therapeutic strategies based on the current research findings to ensure the interchange between the ideal pyroptosis and cancer cell death.
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.
Harnessing the dual role of polysaccharides in treating gastrointestinal diseases: As therapeutics and polymers for drug delivery

Corrie L, Gulati M, Awasthi A, Vishwas S, Kaur J, Khursheed R, et al.

Chem Biol Interact, 2022 Dec 01;368:110238.
PMID: 36306865 DOI: 10.1016/j.cbi.2022.110238

Polysaccharides (PS) represent a broad class of polymer-based compounds that have been extensively researched as therapeutics and excipients for drug delivery. As pharmaceutical carriers, PS have mostly found their use as adsorbents, suspending agents, as well as cross-linking agents for various formulations such as liposomes, nanoparticles, nanoemulsions, nano lipid carriers, microspheres etc. This is due to inherent properties of PS such as porosity, steric stability and swellability, insolubility in pH. There have been emerging reports on the use of PS as therapeutic agent due to its anti-inflammatory and anti-oxidative properties for various diseases. In particular, for Crohn's disease, ulcerative colitis and inflammatory bowel disease. However, determining the dosage, treatment duration and effective technology transfer of these therapeutic moieties have not occurred. This is due to the fact that PS are still at a nascent stage of development to a full proof therapy for a particular disease. Recently, a combination of polysaccharide which act as a prebiotic and a probiotic have been used as a combination to treat various intestinal and colorectal (CRC) related diseases. This has proven to be beneficial, has shown good in vivo correlation and is well reported. The present review entails a detailed description on the role of PS used as a therapeutic agent and as a formulation pertaining to gastrointestinal diseases.
Applications and advancements of nanoparticle-based drug delivery in alleviating lung cancer and chronic obstructive pulmonary disease

De Rubis G, Paudel KR, Corrie L, Mehndiratta S, Patel VK, Kumbhar PS, et al.

Naunyn Schmiedebergs Arch Pharmacol, 2024 May;397(5):2793-2833.
PMID: 37991539 DOI: 10.1007/s00210-023-02830-w

Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) are among the leading causes of mortality worldwide. Cigarette smoking is among the main aetiologic factors for both ailments. These diseases share common pathogenetic mechanisms including inflammation, oxidative stress, and tissue remodelling. Current therapeutic approaches are limited by low efficacy and adverse effects. Consequentially, LC has a 5-year survival of < 20%, while COPD is incurable, underlining the necessity for innovative treatment strategies. Two promising emerging classes of therapy against these diseases include plant-derived molecules (phytoceuticals) and nucleic acid-based therapies. The clinical application of both is limited by issues including poor solubility, poor permeability, and, in the case of nucleic acids, susceptibility to enzymatic degradation, large size, and electrostatic charge density. Nanoparticle-based advanced drug delivery systems are currently being explored as flexible systems allowing to overcome these limitations. In this review, an updated summary of the most recent studies using nanoparticle-based advanced drug delivery systems to improve the delivery of nucleic acids and phytoceuticals for the treatment of LC and COPD is provided. This review highlights the enormous relevance of these delivery systems as tools that are set to facilitate the clinical application of novel categories of therapeutics with poor pharmacokinetic properties.