Nanosponges-Road Less Explored Changing Drug Delivery Approach: An Explicative Review.

Nanotechnology exhibits a wide range of applications in the domain of disease therapy, diagnosis, biological detection, and environmental safeguards. The cross-linked polymeric nanosponges (NSs) are a nanoscale drug carrier system with a 3D porous structure and high entrapment efficacy. NSs up to the fourth generation are currently accessible and can serve as a delivery system for both hydrophilic and hydrophobic drugs. The delivery system exhibits superiority over alternative methods due to its ability to achieve controlled and targeted drug delivery. The colloidal structure of NSs facilitates the encapsulation of a wide range of agents such as proteins and peptides, enzymes, antineoplastic drugs, volatile oil, vaccines, DNA, etc. NSs efficiently overcome the challenges associated with drug toxicity and poor aqueous solubility. NS formulations have been explored for various applications like gaseous encapsulation, enzyme immobilization, antifungal therapy, poison absorbent, water purification, etc. This review provides a comprehensive analysis regarding methods of synthesis, distinct polymeric NSs, mechanism of drug release, factors affecting NS development, applications, and patents filed in the field of NSs. Herein, the recently developed NS formulations, their potential in cancer therapy, and current progressions of NS for SARS-CoV-2 management are also deliberated with special attention, focusing on the significant challenges and future directions.

An Insight into Cubosomal Drug Delivery Approaches: An Explicative Review.

Cubosomes, a novel drug delivery system, have gained significant attention in recent years due to their unique self-assembled structures and enhanced drug encapsulation capabilities. They are administered by oral, ophthalmic, transdermal, and chemotherapeutic routes, to name a few. Due to their many potential benefits-which include high drug dispersal due to the cubic structure, a large surface area, a relatively simple manufacturing process, biodegradability, the capacity to encapsulate hydrophobic, hydrophilic, and amphiphilic compounds, targeted and controlled release of bioactive agents, and the biodegradability of lipids-cubosomes show enormous promise in drug nanoformulations for cancer therapeutics. The most common preparation method involves emulsifying a monoglyceride with a polymer, homogenizing, and then sonicating the mixture. Two distinct approaches to preparing are top-down and bottom-up. This evaluation will examine the materials, methods of preparation, cubosome-related drug encapsulating techniques, drug loading, release mechanism, and their uses. The following databases were used for literature searches: PubMed, Frontiers, Science Direct, Springer, Wiley, and MDPI. For the purpose of finding pertinent articles and contents (2015-2024), the keywords "cubosome; drug delivery systems, nano-carrier, theranostic, drug release mechanism" and others of a similar nature were utilized. This review will conduct a comprehensive analysis of the cubosome-related composition, production methods, drug encapsulating strategies, drug release mechanisms, and applications. Moreover, the difficulties encountered in fine-tuning different parameters to improve loading capabilities and prospects are also discussed. Innovation in pharmaceutical research and development can be stimulated by the knowledge gathered about cubosomal drug delivery methods. Through the clarification of the mechanisms involved in drug release from cubosomes and the investigation of innovative fabrication procedures, scientists can enhance the cubosomal formulation design for targeted therapeutic uses.

Role of PIM Kinase Inhibitor in the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD), a neurodegenerative disorder, is the most prevalent form of senile dementia, causing progressive deterioration of cognition, behavior, and rational skills. Neuropathologically, AD is characterized by two hallmark proteinaceous aggregates: amyloid beta (Aß) plaques and neurofibrillary tangles (NFTs) formed of hyperphosphorylated tau. A significant study has been done to understand how Aß and/or tau accumulation can alter signaling pathways that affect neuronal function. A conserved protein kinase known as the mammalian target of rapamycin (mTOR) is essential for maintaining the proper balance between protein synthesis and degradation. Overwhelming evidence shows mTOR signaling's primary role in age-dependent cognitive decline and the pathogenesis of AD. Postmortem human AD brains consistently show an upregulation of mTOR signaling. Confocal microscopy findings demonstrated a direct connection between mTOR and intraneuronal Aß42 through molecular processes of PRAS40 phosphorylation. By attaching to the mTORC1 complex, PRAS40 inhibits the activity of mTOR. Furthermore, inhibiting PRAS40 phosphorylation can stop the Aß-mediated increase in mTOR activity, indicating that the accumulation of Aß may aid in PRAS40 phosphorylation. Physiologically, PRAS40 is phosphorylated by PIM1 which is a serine/threonine kinase of proto-oncogene PIM kinase family. Pharmacological inhibition of PIM1 activity prevents the Aß-induced mTOR hyperactivity in vivo by blocking PRAS40 phosphorylation and restores cognitive impairments by enhancing proteasome function. Recently identified small-molecule PIM1 inhibitors have been developed as potential therapeutic to reduce AD-neuropathology. This comprehensive study aims to address the activity of PIM1 inhibitor that has been tested for the treatment of AD, in addition to the pharmacological and structural aspects of PIM1.

Smart Multifunctional Nanoparticles in Cancer Theranostics: Progress and Prospect.

BACKGROUND: Worldwide, cancer is the second most common cause of death. Chemotherapy and other traditional cancer treatments have toxicities that affect normal cells in addition to their intended targets, necessitating the development of novel approaches to enhance cell-specific targeting. METHODS: The present work summarizes the scientific information on nanoparticles in cancer theranostics to provide a comprehensive insight into the preventive and therapeutic potential of nanoparticles in cancer. Scopus, PubMed, Science Direct, and Google Scholar databases are searched to collect all the recent (2015-2023) scientific information on smart multifunctional nanoparticles using the terms nanotechnology, cancer theranostics, and polymer. RESULTS: The use of nanomaterials as chemical biology tools in cancer theranostics has been thoroughly investigated. They demonstrate expanded uses in terms of stability, biocompatibility, and enhanced cell permeability, enabling precision targeting and ameliorating the drawbacks of conventional cancer treatments. The nano platform presents a fascinating chance to acquire multifunctionality and targeting techniques. The production of smart nanomaterials, specifically with regard to the advent of nanotechnology, has revolutionized the diagnosis and treatment of cancer. The capability of nanoparticles to functionalize with a variety of biosubstrates, including aptamers, antibodies, DNA, and RNA, and their broad surface area allow them to encapsulate a huge number of molecules, contributing to their theranostic effect. Comparatively speaking, economical, easily produced, and less toxic nanomaterials formed from biological sources are thought to have benefits over those made using conventional processes. CONCLUSION: The present study highlights the uses of several nanoparticles (NPs), and describes numerous cancer theranostics methodologies. The benefits and difficulties preventing their adoption in cancer treatment and diagnostic applications are also critically reviewed. The use of smart nanomaterials, according to this review's findings, can considerably advance cancer theranostics and open up new avenues for tumor detection and treatment.

Nanotechnology-Powered Meningitis Therapies: Lipid Nanoparticles Lead the Way.

The meninges serve as a protective layer, and the fluid around the brain and spinal cord can become inflamed, known as meningitis. Lipid-based pharmaceutical formulations, by their high lipophilicity, can negotiate the Blood-Brain Barrier (BBB). The current mode of treatment of meningitis is mainly through antibiotics, which, at best, is partially effective. The success of antibiotic therapy depends on several factors, for example, the difficulty of reaching the infection site, maintaining proper concentrations of the drug after crossing the BBB, and finally, its efficacy in preventing recurrent infection. In this context, interest has focused on organic and inorganic nanostructures for meningitis and transporting antibiotics to the selected region through the BBB. A focus has also been placed on several polymeric nanotechnology techniques for detecting various types of meningitis. This review focuses on nano interventions and their most recent meningitis treatments using nanotechnology.

Unlocking the Potential of RNA Nanoparticles: A Breakthrough Approach to Overcoming Challenges in Colon Cancer Treatment.

Globally, one of the leading causes of cancer-related deaths is colon cancer. As this form of cancer has a tremendous potential to metastasize, effective treatment is complicated and sometimes impossible. Despite the improvement of conventional chemotherapy and the advent of targeted therapies, overcoming multi-drug resistance (MDR) and side effects remain significant challenges. As a therapeutic intervention for targeted gene silencing in cancer, RNA technology shows promise and certain RNA-based formulations are currently undergoing clinical studies. Various studies have reported that RNA-based nanoparticles have demonstrated substantial promise for targeted medication delivery, gene therapy, and other biomedical applications. However, using RNA as a therapeutic tool presents severe limitations, mainly related to its low stability and poor cellular uptake. Nanotechnology offers a flexible and tailored alternative due to the difficulties in delivering naked RNA molecules safely in vivo, such as their short half-lives, low chemical stability, and susceptibility to nuclease degradation. In addition to shielding RNA molecules from immune system attacks and enzymatic breakdown, the nanoparticle-based delivery systems allow RNA accumulation at the tumor site. The potential of RNA and RNA-associated nanomedicines for the treatment of colon cancer, as well as the prospects for overcoming any difficulties related to mRNA, are reviewed in this study, along with the current progress of mRNA therapeutics and advancements in designing nanomaterials and delivery strategies.

Emerging therapeutic strategies in cancer therapy by HDAC inhibition as the chemotherapeutic potent and epigenetic regulator.

In developing new cancer medications, attention has been focused on novel epigenetic medicines called histone deacetylase (HDAC) inhibitors. Our understanding of cancer behavior is being advanced by research on epigenetics, which also supplies new targets for improving the effectiveness of cancer therapy. Most recently published patents emphasize HDAC selective drugs and multitarget HDAC inhibitors. Though significant progress has been made in emerging HDAC selective antagonists, it is urgently necessary to find new HDAC blockers with novel zinc-binding analogues to avoid the undesirable pharmacological characteristics of hydroxamic acid. HDAC antagonists have lately been explored as a novel approach to treating various diseases, including cancer. The complicated terrain of HDAC inhibitor development is summarized in this article, starting with a discussion of the many HDAC isotypes and their involvement in cancer biology, followed by a discussion of the mechanisms of action of HDAC inhibitors, their current level of development, effect of miRNA, and their combination with immunotherapeutic.

Unveiling Spanlastics as a Novel Carrier for Drug Delivery: A Review.

Innovative colloidal preparations that can alter the pharmacological properties of drugs have been made possible by the advancement of nanotechnology. Recent advances in the sciences of the nanoscale have led to the creation of new methods for treating illnesses. Developments in nanotechnology may lessen the side effects of medicine by using effective and regulated drug delivery methods. A promising drug delivery vehicle is spanlastics, an elastic nanovesicle that can transport a variety of drug compounds. Spanlastics have expanded the growing interest in many types of administrative pathways. Using this special type of vesicular carriers, medications intended for topical, nasal, ocular, and trans-ungual treatments are delivered to specific areas. Their elastic and malleable structure allows them to fit into skin pores, making them ideal for transdermal distribution. Spanlastic is composed of non-ionic surfactants or combinations of surfactants. Numerous studies have demonstrated how spanlastics significantly improve, drug bioavailability, therapeutic effectiveness, and reduce medication toxicity. The several vesicular systems, composition and structure of spanlastics, benefits of spanlastics over alternative drug delivery methods, and the process of drug penetration via skin are all summarized in this paper. Additionally, it provides an overview of the many medications that may be treated using spanlastic vesicles. The primary benefits of these formulations were associated with their surface properties, as a variety of proteins might be linked to the look. For instance, procedure assessment and gold nanoparticles were employed as biomarkers for different biomolecules, which included tumor label detection. Anticipate further advancements in the customization and combining of spanlastic vesicles with appropriate zeta potential to transport therapeutic compounds to specific areas for enhanced disease treatment.

A Promising Drug Candidate as Potent Therapeutic Approach for Neuroinflammation and Its In Silico Justification of Chalcone Congeners: a Comprehensive Review.

Multiple genetic, environmental, and immunological variables cause neuropsychiatric disorders (NPDs). The induced inflammatory immune response is also connected to the severity and treatment outcomes of various NPDs. These reactions also significantly impact numerous brain functions such as GABAergic signaling and neurotransmitter synthesis through inflammatory cytokines and chemokines. Chalcones (1,3-diaryl-2-propen-1-ones) and their heterocyclic counterparts are flavonoids with various biological characteristics including anti-inflammatory activity. Several pure chalcones have been clinically authorized or studied in humans. Chalcones are favored for their diagnostic and therapeutic efficacy in neuroinflammation due to their tiny molecular size, easy manufacturing, and flexibility for changes to adjust lipophilicity ideal for BBB penetrability. These compounds reached an acceptable plasma concentration and were well-tolerated in clinical testing. As a result, they are attracting increasing attention from scientists. However, chalcones' therapeutic potential remains largely untapped. This paper is aimed at highlighting the causes of neuroinflammation, more potent chalcone congeners, their mechanisms of action, and relevant structure-activity relationships.

Deciphering the molecular mechanistic paths describing the chemotherapeutic potential and epigenetic regulation of curcumin in lung cancer: a mini review.

In an uncontrolled inflammatory environment, the complex process of lung carcinogenesis occurs. Lung cancer remains the leading cause of cancer-related mortality worldwide. The average 5-year survival rate is still low despite significant advancements in our knowledge of lung carcinogenesis and the development of innovative therapies in recent decades. Research on adjuvant treatment, lung carcinogenesis pathways, and possible prognostic indicators has to be refocused using an innovative approach. The majority of lung cancers are discovered at an advanced stage when there is little chance of recovery. It has grown in popularity in recent years to supplement already available chemotherapeutic therapies with adjuvant herbal medications, which may lessen toxicity and adverse effects without sacrificing therapeutic efficiency. One such prospective contender is curcumin. In-depth research has been done on curcumin as a multi-target anti-tumor and anti-inflammatory molecule. A pharmacologically active polyphenol produced from turmeric is called curcumin. Over the past few decades, curcumin's therapeutic potential has been thoroughly studied, and data indicate that curcumin may play a part in a variety of biological processes, most notably its potent anticancer activity. Being a pleiotropic chemical, curcumin regulates a variety of molecules that are key players in many cell signaling pathways. It has been shown to stifle transformation, restrain proliferation, and trigger apoptosis. Curcumin can reduce the development of non-small cell LC by downregulating Circular RNA hsa_circ_0007580, which in turn controls the expression of integrin subunit beta 1 by adsorbing miR-384. Nevertheless, despite all these advantages, curcumin's effectiveness is still restricted because of its weak bioavailability, poor absorption within the systemic circulation, and quick removal from the body. In an effort to overcome these constraints, scientists from all around the world are working to develop a synthetic and improved curcuminoid by appropriately altering the parent skeleton structurally. These curcuminoids will simultaneously improve the physicochemical properties and efficacy. This review presents evidence from the most recent clinical trials coupled with the molecular mechanisms of curcumin in LC. Curcumin as inhibitor of multiple signaling pathways expressed in lung cancer.

An Explicative Review on the Current Advancement in Schiff Base-Metal Complexes as Anticancer Agents Evolved in the Past Decade: Medicinal Chemistry Aspects.

In the recent era, developments in the field of bio-inorganic chemistry have improved interest in Schiff base complexes (imine scaffolds) for their pharmacological excellence in different areas. Schiff bases are a kind of synthetic molecule that is synthesized by the condensation reaction between a 1o amine and a carbonyl compound. Imine derivatives are also acknowledged for their ability to form complexes with several metals. Due to their wide range of biological activities, they have acquired prominence in the therapeutic and pharmaceutical industries. Inorganic chemists have continued to be intrigued by the vast range of uses of these molecules. Many of them are also thermally stable and have structural flexibility. Some of these chemicals have been discovered to be beneficial as clinical diagnostic agents as well as chemotherapeutic agents. Because of the flexibility of the reactions, these complexes have a wide range of characteristics and applications in biological systems. Anti-neoplastic activity is one of them. This review attempts to draw attention to the most notable examples of these novel compounds, which have excellent anticancer activity against different cancers. The synthetic scheme of these scaffolds, their metal complexes, and the explanation of their anticancer mechanism reported in this paper lead the researchers to design and synthesize more target-specific Schiff base congeners with little or no side effects in the future.

Molecular and Structural Insight into Adenosine A2A Receptor in Neurodegenerative Disorders: A Significant Target for Efficient Treatment Approach.

All biological tissues and bodily fluids include the autacoid adenosine. The P1 class of purinergic receptors includes adenosine receptors. Four distinct G-protein-coupled receptors on the cellular membrane mediate the effects of adenosine, whose cytoplasmic content is regulated by producing/degrading enzymes and nucleoside transporters. A2A receptor has received a great deal of attention in recent years because it has a wide range of potential therapeutic uses. A2B and, more significantly, A2A receptors regulate numerous physiological mechanisms in the central nervous system (CNS). The inferior targetability of A2B receptors towards adenosine points that they might portray a promising medicinal target since they are triggered only under pharmacological circumstances (when adenosine levels rise up to micromolar concentrations). The accessibility of specific ligands for A2B receptors would permit the exploration of such a theory. A2A receptors mediate both potentially neurotoxic and neuroprotective actions. Hence, it is debatable to what extent they play a role in neurodegenerative illnesses. However, A2A receptor blockers have demonstrated clear antiparkinsonian consequences, and a significant attraction exists in the role of A2A receptors in other neurodegenerative disorders. Amyloid peptide extracellular accumulation and tau hyperphosphorylation are the pathogenic components of AD that lead to neuronal cell death, cognitive impairment, and memory loss. Interestingly, in vitro and in vivo research has shown that A2A adenosine receptor antagonists may block each of these clinical symptoms, offering a crucial new approach to combat a condition for which, regrettably, only symptomatic medications are currently available. At least two requirements must be met to determine whether such receptors are a target for diseases of the CNS: a complete understanding of the mechanisms governing A2A-dependent processes and the availability of ligands that can distinguish between the various receptor populations. This review concisely summarises the biological effects mediated by A2A adenosine receptors in neurodegenerative disorders and discusses the chemical characteristics of A2A adenosine receptor antagonists undergoing clinical trials. Selective A2A receptor blocker against neurodegenerative disorders.

A toxicological evaluation for safety assessment of ruthenium-based diosmetin complex in rats.

The flavonoid-based organometallic complexes have been identified as novel bioactive compounds with enhanced pharmacological and therapeutic activity. In this study, the ruthenium-p-cymene diosmetin complex was synthesized, characterized, and investigated for toxicological profiling through different toxicological and genotoxicological studies which include acute and sub-acute toxicity, chromosomal aberration, and bone marrow micronucleus study. The acute oral toxicity study demonstrated the LD50 dose of the complex at 500 mg/kg body weight which further instigated the sub-acute doses i.e. 50, 100, and 200 mg/kg. The histopathological analysis demonstrated that the 400 mg/kg dose was associated with severe toxicological incidences of the vital organs (liver, kidney, pancreas, testis, and stomach) except the ovary with increased levels of ALP, AST, ALT, and WBC count. However, 50, 100, and 200 mg/kg doses did not show any toxicological alteration and maintained the normal levels of hematological and serum biochemical parameters. The genotoxicological assessment of the complex depicted no such genetic damage or mutagenicity in any complex treated groups. In conclusion, the 50, 100, and 200 mg/kg doses were determined as therapeutic dose of the novel ruthenium-p-cymene diosmetin complex without any genotoxic and mutagenic potential which can be further implemented in the investigation of various pharmacological and therapeutic interventions.

Design and evaluation of itraconazole loaded solid lipid nanoparticulate system for improving the antifungal therapy.

The objective of the study was to design and evaluate itraconazole loaded solid lipid nanoparticles (SLNs) drug delivery system, where itraconazole nanoparticles with suitable size ranges are expected to improve the therapeutic efficacy and reduction of toxicity of this broad spectrum antifungal agent. Components of the SLNs were lipid (palmitic acid) and surfactants (Pluronic F127 and Tween 40). The itraconazole loaded nanoparticles were prepared by microemulsion dispersion method. Experiments were carried out with optimized ratio of excipients, where drug-lipid ratio and surfactant-cosurfactant ratio (Km) were varied to optimize the formulation characteristics. The effects of dispersion media, its pH, ionic content, etc. were investigated to optimize the SLNs production. Particles size analysis and zeta potential measurements were done using Malvern Mastersizer Hydro 2000G. The particles were also subjected to DSC, IR and XRD analyses. The in vitro drug release profile from nanoparticles was found to prolong up to 12 h. Kinetic analysis of release indicated that nanoparticles formed were matrix in nature, in which Itraconazole dispersed uniformly. Optimized formulations were found to have a lipid-drug ratio of 1.5:1 and prepared at a Km ratio of 1:2 to maximize drug loading, modulate release and minimized particle size. The microemulsion mediated nanoparticle preparation methodology ensured high drug loading (ca. 80%), low and narrow size distribution and provided a reproducible and fast production method. The study elaborates on the feasibility and suitability of lipid based colloidal drug delivery system, employing optimize design to develop a clinically useful nanoparticle system with targeting potential.