Targeting brain tumors with innovative nanocarriers: bridging the gap through the blood-brain barrier.

Background: Glioblastoma multiforme (GBM) is recognized as the most lethal and most highly invasive tumor. The high likelihood of treatment failure arises from the presence of the blood-brain barrier (BBB) and stem cells around GBM, which avert the entry of chemotherapeutic drugs into the tumor mass. Objective: Recently, several researchers have designed novel nanocarrier systems like liposomes, dendrimers, metallic nanoparticles, nanodiamonds, and nanorobot approaches, allowing drugs to infiltrate the BBB more efficiently, opening up innovative avenues to prevail over therapy problems and radiation therapy. Methods: Relevant literature for this manuscript has been collected from a comprehensive and systematic search of databases, for example, PubMed, Science Direct, Google Scholar, and others, using specific keyword combinations, including "glioblastoma," "brain tumor," "nanocarriers," and several others. Conclusion: This review also provides deep insights into recent advancements in nanocarrier-based formulations and technologies for GBM management. Elucidation of various scientific advances in conjunction with encouraging findings concerning the future perspectives and challenges of nanocarriers for effective brain tumor management has also been discussed.

Monoclonal antibodies and antibody-drug conjugates as emerging therapeutics for breast cancer treatment.

When breast cells divide and multiply out of control, it is called breast cancer. Symptoms include lump formation in the breast, a change in the texture or color of the breast, or a discharge from the nipple. Local or systemic therapy is frequently used to treat breast cancer. Surgical and radiation procedures limited to the affected area are examples of local management. There has been significant worldwide progress in the development of monoclonal antibodies (mAbs) since 1986, when the first therapeutic mAb, Orthoclone OKT3, became commercially available. mAbs can resist the expansion of cancer cells by inducing the destruction of cellular membranes, blocking immune system inhibitors, and preventing the formation of new blood vessels. mAbs can also target growth factor receptors. Understanding the molecular pathways involved in tumor growth and its microenvironment is crucial for developing effective targeted cancer therapeutics. Due to their unique properties, mAbs have a wide range of clinical applications. Antibody-drug conjugates (ADCs) are drugs that improve the therapeutic index by combining an antigen-specific antibody with a payload. This review focuses on the therapeutic applications, mechanistic insights, characteristics, safety aspects, and adverse events of mAbs like trastuzumab, bevacizumab, pertuzumab, ertumaxomab, and atezolizumab in breast cancer treatment. The creation of novel technologies utilizing modified antibodies, such as fragments, conjugates, and multispecific antibodies, must be a central focus of future studies. This review will help scientists working on developing mAbs to treat cancers more effectively.

Designing lisuride intranasal nanocarrier system for reduction of oxidative damage with enhanced dopamine level in brain for Parkinsonism.

In the present study, nanoemulsion (NE) loaded with lisuride were formulated for delivering drug to brain via intranasal route. Dopamine levels, pharmacokinetic, and antioxidant activity were estimated. Antioxidant effect of lisuride NE was assessed in-vivo using oxidative stress models revealing symptoms like those of Parkinson's disease. Intranasally administered lisuride NE-treated group revealed a greater number of antioxidant enzymes, such as superoxide dismutase (SOD) and glutathione (GSH) as compared to the intravenously administered lisuride suspension in haloperidol rat model. Additionally, it was observed that lisuride NE can decrease dopamine loss. When lisuride NE was administered intranasally resulted in considerably higher dopamine concentrations (17.48 ± 0.05 ng/mL) in comparison to rats receiving haloperidol (7.28 ± 0.02 ng/mL). From study, it is suggested that NE is a possible strategy to deliver lisuride intranasally to lower free radical damage and prevent the biochemical alterations associated with Parkinson's disease.

Recent Insights into Osimertinib Analogues against EGFR Positive Non-small Cell Lung Cancer.

BACKGROUND: Lung cancer is a highly lethal malignancy with a poor prognosis and the leading cause of mortality worldwide. The development of mutations makes lung cancer treatment more challenging and expensive. Successful identification of epidermal growth factor receptor (EGFR) mutations led to the discovery of various third-generation tyrosine kinase inhibitors. Osimertinib is one of the promising and efficacious third-generation EGFR inhibitors and is mainly employed in the treatment of non-small cell lung cancer. Despite the initial effective response, osimertinib causes resistance in most of the patients after around 10 months of therapy, resulting in disease progression. To mitigate the effect of developed resistance, different osimertinib derivatives have been synthesized and evaluated by numerous research groups across the globe. METHODS: Present article illustrates recent research advancements for the utilization of osimertinib and its derivatives in non-small cell lung cancer (NSCLC). Last seven years literature search has been conducted from PubMed, ScienceDirect, and Google Scholar databases, etc. Result: The present review emphasizes the recent advancements of osimertinib analogues that lead to enhanced antitumor potential and safety profile against non-small cell lung cancer. This manuscript also summarizes the different synthetic schemes involved in the synthesis of osimertinib analogues against EGFR reported by different research groups. CONCLUSION: Anticancer mechanistic insights, analytical prospects, drug interactions, pharmacokinetic considerations, and resistance profile of osimertinib are highlighted in the current manuscript.

Potential of nanoemulsions for accelerated wound healing: innovative strategies.

Wounds represent various significant health concerns for patients and also contribute major costs to healthcare systems. Wound healing comprises of overlapped and various coordinated steps such as homeostasis, inflammation, proliferation, and remodeling. In response to the failure of many strategies in delivering intended results including wound closure, fluid loss control, and exhibiting properties such as durability, targeted delivery, accelerated action, along with histocompatibility, numerous nanotechnological advances have been introduced. To understand the magnitude of wound therapy, this systematic and updated review discussing the effectiveness of nanoemulsions has been undertaken. This review portrays mechanisms associated with wound healing, factors for delayed wound healing, and various technologies utilized to treat wounds effectively. While many strategies are available, nanoemulsions have attracted the tremendous attention of scientists globally for the research in wound therapy due to their long-term thermodynamic stability and bioavailability. Nanoemulsions not only aid in tissue repair, but are also considered as an excellent delivery system for various synthetic and natural actives. Nanotechnology provides several pivotal benefits in wound healing, including improved skin permeation, controlled release, and stimulation of fibroblast cell proliferation. The significant role of nanoemulsions in improved wound healing along with their preparation techniques has also been highlighted with special emphasis on mechanistic insights. This article illustrates recent research advancements for the utilization of nanoemulsions in wound treatment. An adequate literature search has been conducted using the keywords 'Nanoemulsions in wound healing', 'Wound therapy and nanoemulsions', 'Herbal actives in wound therapy', 'Natural oils and wounds treatment' etc., from PubMed, Science Direct, and Google Scholar databases. Referred and original publications in the English language accessed till April 2022 has been included, whereas nonEnglish language papers, unpublished data, and nonoriginal papers were excluded from the study.

A Review on Polymeric Nanostructured Micelles for the Ocular Inflammation-Main Emphasis on Uveitis.

BACKGROUND: Various types of nano-formulations are being developed and tested for the delivery of the ocular drug. They also have anatomical and physiological limitations, such as tear turnover, nasal lachrymal waste, reflex squinting, and visual static and dynamic hindrances, which pose challenges and delay ocular drug permeation. As a result of these limitations, less than 5% of the dose can reach the ocular tissues. OBJECTIVE: The basic purpose of designing these formulations is that they provide prolonged retention for a longer period and can also increase the course time. METHODS: To address the aforementioned issues, many forms of polymeric micelles were developed. Direct dissolving, dialysis, oil-in-water emulsion, solvent evaporation, co-solvent evaporation, and freeze-drying are some of the methods used to make polymeric nano micelles. RESULTS: Their stability is also very good and also possesses reversible drug loading capacity. When the drug is given through the topical route, then it has very low ocular bioavailability. CONCLUSION: The definition and preparation process of polymeric micelles and anti-inflammatory drugs used in uveitis and the relation between uveitis and micelles are illustrated in detail.

Polysaccharide-based hydrogels: New insights and futuristic prospects in wound healing.

Polysaccharides elicit enormous and promising applications due to their extensive obtainability, innocuousness, and biodegradability. Various outstanding features of polysaccharides can be employed to fabricate biomimetic and multifunctional hydrogels as efficient wound dressings. These hydrogels mimic the natural extracellular matrix and also boost the proliferation of cells. Owing to distinctive architectures and abundance of functional groups, polysaccharide-derived hydrogels have exceptional physicochemical properties and unique therapeutic interventions. Hydrogels designed using polysaccharides can effectively safeguard wounds from bacterial attack. This review includes wound physiology and emphasises on numerous polysaccharide-based hydrogels for wound repair applications. Polysaccharide hydrogels for different wound types and diverse therapeutic agents loaded in hydrogels for wound repair with recent patents are portrayed in the current manuscript, debating the potential of fascinating hydrogels for effective wound healing. More research is required to engineer multifaceted advanced polysaccharide hydrogels with tuneable and adjustable properties to attain huge potential in wound healing.

Mechanistic Insights into the Pharmacological Significance of Silymarin.

Medicinal plants are considered the reservoir of diverse therapeutic agents and have been traditionally employed worldwide to heal various ailments for several decades. Silymarin is a plant-derived mixture of polyphenolic flavonoids originating from the fruits and akenes of Silybum marianum and contains three flavonolignans, silibinins (silybins), silychristin and silydianin, along with taxifolin. Silybins are the major constituents in silymarin with almost 70-80% abundance and are accountable for most of the observed therapeutic activity. Silymarin has also been acknowledged from the ancient period and is utilized in European and Asian systems of traditional medicine for treating various liver disorders. The contemporary literature reveals that silymarin is employed significantly as a neuroprotective, hepatoprotective, cardioprotective, antioxidant, anti-cancer, anti-diabetic, anti-viral, anti-hypertensive, immunomodulator, anti-inflammatory, photoprotective and detoxification agent by targeting various cellular and molecular pathways, including MAPK, mTOR, ß-catenin and Akt, different receptors and growth factors, as well as inhibiting numerous enzymes and the gene expression of several apoptotic proteins and inflammatory cytokines. Therefore, the current review aims to recapitulate and update the existing knowledge regarding the pharmacological potential of silymarin as evidenced by vast cellular, animal, and clinical studies, with a particular emphasis on its mechanisms of action.

WITHDRAWN: Pharmaceutical Nanoemulsion System: A Strategy to Enhance the Bioavailability of Drugs

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Melphalan: Recent insights on synthetic, analytical and medicinal aspects.

Cancer is an uncontrolled expansion of atypical cells in the body. These unusual cells are labelled as cancerous or malignant cells. Melphalan, an anticancer drug which is imperatively recognized under the class of alkylating agents. It exhibits broad spectrum antitumor activity, as observed in ovarian cancer, breast cancer, etc. However, it is mainly utilized in the management of multiple myeloma. Several studies across the globe suggest that resistance to melphalan is the major concern that leads to relapsed myeloma. In the present paper, several pivotal approaches to compensate resistance associated with melphalan have been discussed. Numerous chemical and formulation developments concerning melphalan to enhance its salient characteristics and targeted profile have also been portrayed. The rationale of the current article also summarizes the recent analytical methods, structure-activity relationship, pharmacokinetics, interactions, potential adverse effects along with medicinal updates of melphalan. Special attention is also laid on their synthetic developments viz. melphalan derivatives, conjugates and prodrugs along with encouraging insights and research findings.

Self-Assembly Polymeric Nano Micelles for the Futuristic Treatment of Skin Cancer and Phototoxicity: Therapeutic and Clinical Advancement.

In the last few years, the polymeric micelles played a major role as a drug carrier in nano-sized drug delivery system. The polymeric micelles are designed from synthetic block co-polymers and graft copolymers. In the mixed micelles, the bilayer lipid membrane and surfactants are used. Both micelles are in nano-sized and used to enhance the drug delivery to treat different diseases. In this review, we will discuss some examples from the literature included demonstrating the polymeric micelles used as drug-carriers in skin cancer treatment by using different drugs. We also summarized mixed micelles, polymeric micelles in skin drug delivery, various polymers, and techniques of polymeric micelles. These micelles may improve delivery of drug in the skin's targeted sites in specific and dermatological diseases like skin cancer, acne, and fungal infection. In the comparison of surfactant micelles, the polymeric micelles are more stable. Polymeric micelles act as a colloidal carrier for incorporating poorly water-soluble and amphiphilic drugs.

Drug Delivery Strategies and Biomedical Significance of Hydrogels: Translational Considerations.

Hydrogels are a promising and attractive option as polymeric gel networks, which have immensely fascinated researchers across the globe because of their outstanding characteristics such as elevated swellability, the permeability of oxygen at a high rate, good biocompatibility, easy loading, and drug release. Hydrogels have been extensively used for several purposes in the biomedical sector using versatile polymers of synthetic and natural origin. This review focuses on functional polymeric materials for the fabrication of hydrogels, evaluation of different parameters of biocompatibility and stability, and their application as carriers for drugs delivery, tissue engineering and other therapeutic purposes. The outcome of various studies on the use of hydrogels in different segments and how they have been appropriately altered in numerous ways to attain the desired targeted delivery of therapeutic agents is summarized. Patents and clinical trials conducted on hydrogel-based products, along with scale-up translation, are also mentioned in detail. Finally, the potential of the hydrogel in the biomedical sector is discussed, along with its further possibilities for improvement for the development of sophisticated smart hydrogels with pivotal biomedical functions.

Carbon Quantum Dots: Synthesis, Characterization and Biomedical Applications.

CQD are small carbon nanoparticles smallerl than 10 nm comprising distinctive properties, which have become an obligatory tool for traceable targeted delivery, biomedical research, and different therapy applications. The objective of the present work was to consolidate the current literature on the synthesis, characterization techniques, and biomedical applications of CQD. Two types of synthetic methods viz. top-down approach and bottom-up approach were used for the synthesis of CQD. The top-down approach includes the arc-discharge method, laser ablation method, and electrochemical method. The bottom-up approach includes the thermal method, microwave-assisted method, hydrothermal and aqueous method, and the template method. In this review, we explain the recent progress of CQD in the biomedical field, focusing on their synthetic methods and characterization, followed by different applications. Carbon dots have extensive adequacy for in vivo and in vitro bioimaging and drug delivery studies. Although more cytotoxicity studies of carbon dots are needed, the data above suggest a bright future for carbon dots in drug delivery and bioimaging studies.

Insight into Prodrugs of Quinolones and Fluoroquinolones.

Quinolones and fluoroquinolones are principal weapons against variety of bacterial infections and exert their antibacterial potential by interfering the activities of bacterial enzymes. As these agents are associated with some limitations, an important approach to overcome these major constraints is to prepare covalent derivatives, i.e. prodrugs. Prodrug design has been employed to improve the limitations of these drugs such as less aqueous solubility, poor absorption and distribution, toxicity, disagreeable taste, poor lipophilicity etc and for improving their pharmacological profile. This paper highlights the utility of various prodrug strategies in optimizing the therapeutic index of these antibacterial agents and their recent patents. Some of their prodrugs being utilized at preclinical and clinical levels have also been discussed. Hence, this paper has been prepared to present the significant findings of various research papers that would be helpful in motivating scientific researchers to forward the research in direction of utilization of prodrugs in clinical therapy.

Recent advances in gastric floating drug delivery technology: a review.

Gastric floating drug delivery systems have been an avenue of considerable interest in terms of their immense potential for better pharmacotherapeutic interventions along with site-specific absorption. These buoyant systems significantly enhance the bioavailability and controlled delivery of several drug molecules. Scientific investigators have also carried out substantial research endeavours worldwide in order to design a more systematic and intellectual floating systems. The present manuscript is an attempt to highlight numerous recent advancements in the design of gastric floating drug delivery systems along with various available commercial preparations. Salient applications, characterization aspects and future perspectives of these multifarious systems have also been addressed.

Recent advances and patent perspectives in gastroretentive technology.

Gastroretentive drug delivery technology has emerged as an efficient approach for enhancing the bioavailability and controlled delivery of various therapeutic molecules. Myriad of patents issued in the vistas of gastroretentive technology have inspired scientific community worldwide to develop more innovative strategies for the fabrication of drug delivery devices which can be retained in stomach for a controlled period of time. The present paper describes various recent efforts and technological advancements of gastroretentive drug delivery systems along with potential advantages and available marketed preparations. Numerous significant patents concerning gastroretentive drug delivery devices are also highlighted.

Chitosan-based gastroretentive floating drug delivery technology: an updated review.

INTRODUCTION: Gastroretentive floating drug delivery systems have emerged as efficient approaches for enhancing the bioavailability and controlled delivery of various therapeutic agents. Significant advancements exploiting chitosan have been made worldwide, in order to investigate these systems according to patient requirements, both in terms of therapeutic efficacy as well as patient compliance. Such systems precisely control the release rate of the target drug to a specific site, which facilitates an enormous impact on health care. AREAS COVERED: Different novel strategies have been undertaken for the development of various gastric floating dosage forms utilizing chitosan as a promising excipient. The present paper is an earnest attempt to provide new insights on various physicochemical and biological characteristics of chitosan, along with its potential applications in a wide array of biomedical approaches. Numerous and significant research findings in the vistas of chitosan-based gastroretentive floating drug delivery technology are also discussed. EXPERT OPINION: Chitosan has been considered as a unique and efficacious agent possessing a myriad spectrum of desired characteristics. It is emphasized that recent scientific advancements in the use of this excipient as a carrier will yield new generation gastroretentive drug delivery systems, with better pharmacotherapeutic interventions. Further studies are required to unveil the hidden beneficial properties of chitosan and its derivatives, to obtain newer delivery systems which may hold tremendous prospects in the near future.

Ciprofloxacin: review on developments in synthetic, analytical, and medicinal aspects.

In the current practices of anti-infective therapy, ciprofloxacin is a very popular fluoroquinolone having a broad spectrum of activity and diverse therapeutic prospects. The reasons for its wide use include multiresistant pathogens susceptible only to ciprofloxacin. The available clinical evidence suggests the potentially enhanced efficacy of this drug in the treatment of various community acquired and nosocomial infections, e.g. respiratory tract, urinary tract, and skin infections and sexually transmitted diseases. As compared to other agents of its class, the pharmacokinetic profile of ciprofloxacin demonstrates equivalent or greater bioavailability, higher plasma concentrations, and increased tissue penetration, as reflected in the greater volume of distribution. Various molecular modifications of this drug have been made to further improve its characteristics. Several methods of analytical determination of ciprofloxacin and its metabolites in biological fluids employing various techniques have been reported. The present article is focused on the synthetic development, pharmacotherapeutic, and analytical evaluation vistas of ciprofloxacin.