Eugenol-Loaded Transethosomal Gel for Improved Skin Delivery and Treatment of Atopic Dermatitis.

Atopic dermatitis is a skin condition characterized by lichenification (thickening and increased skin marking), eczematous lesions, dry skin, itching, and pruritus. Eugenol is an aromatic polyphenolic compound that has attracted the attention of researchers due to its anti-inflammatory, anti-oxidant, and anti-cancer properties. The primary goal of the present study was to develop and evaluate eugenol-loaded transethosomes for the treatment of AD. Eugenol-loaded transethosomes were formulated using the ethanol injection method and subsequently subjected to particle size analysis, zeta potential, entrapment efficiency, deformability index, and HRTEM analysis. Transethosomal gel was prepared by direct-dispersion method by using Carbopol 940®. Results showed transethosomes to be lipid bilayer structures with acceptable size, and high entrapment efficiency. Transethosomal formulation showed shear-thinning behavior. Eugenol-loaded transethosomal gel was significantly able to enhance the retention of the drug in the skin. Transethosomal gel was significantly able to reduce Ear thickness, DLC, TLC, and IL-6 levels in mice model of AD. These results indicate that the eugenol-loaded transethosomal gel could be a promising carrier for the topical administration of eugenol for the treatment of AD.

Experimental design approach for development of carboplatin loaded chitosan modified liposomal formulation with improved topical vaginal therapeutic potential.

One of the most prevalent cancers affecting women globally is cervical cancer. Cervical cancer is thought to cause 570 000 new cases annually, and standard treatments can have serious side effects. In this work, the main aim is to design, fabrication, and evaluation of carboplatin loaded chitosan coated liposomal formulation (CCLF-I) for vaginal delivery in the treatment of cervical cancer. The particle size and polydispersity index of the CCLF-1 were observed at 269.33 ± 1.15 and 0.40 ± 0.002 nm, respectively. The in vitro mucin binding studies showed good adhesiveness of CCLF-I as compared to plain liposomes (CPLF-I), which was found at 23.49 and 10.80%, respectively. The ex-vivo percent drug permeation from plain liposomal formulation (CPLF-I) was found to be higher in comparison to chitosan coated liposomal formulation which was 56.33% while in CCLF-I it was observed 47.32% this is due to, higher retainability of delivery system (CCLF-I) on targeted site attained by coating of mucoadhesive polymer on liposomes. Ex vivo tissue retention studies exhibited 24.2% of CCLF-I in comparison to 10.34% from plain drug formulation (CPLF-I). The in vivo vaginal retention studies exhibited 14% of drug retention after 24 h from the novel formulation in comparison to 6% from the plain formulation. The developed CCLF-I formulation would open a new avenue in the cervical treatment.

An insight into biosensing platforms used for the diagnosis of various lung diseases: A review.

Many of the infectious diseases are ubiquitous in nature and pose a threat to global and public health. The original cause for such type of serious maladies can be summarized as the scarcity of appropriate analysis and treatment methods. Pulmonary diseases are considered one of the life-threatening lung diseases that affect millions of people globally. It consists of several types, namely, asthma, lung cancer, tuberculosis, chronic obstructive pulmonary disease, and several respiratory-related infections. This is due to the limited access to well-equipped healthcare facilities for early disease diagnosis. This needs the availability of processes and technologies that can help to stop this harmful disease-diagnosing practice. Various approaches for diagnosing various lung diseases have been developed over time, namely, autopsy, chest X-rays, low-dose CT scans, and so forth. The need of the hour is to develop a rapid, simple, portable, and low-cost method for the diagnosis of pulmonary diseases. So nowadays, biosensors have been becoming one of the highest priority research areas as a potentially useful tool for the early diagnosis and detection of many pulmonary lung diseases. In this review article, various types of biosensors and their applications in the diagnosis of lung-related disorders are expansively explained.

Exploring the therapeutic potential of naturally occurring piceatannol in non-communicable diseases.

Piceatannol is a naturally occurring hydroxylated resveratrol analogue that can be found in a variety of fruits and vegetables. It has been documented to have a wide range of beneficial effects, including anti-inflammatory, antioxidant, anti-aging, anti-allergic, antidiabetic, neuroprotective, cardioprotective, and chemopreventive properties. Piceatannol has significantly higher antioxidant activity than resveratrol. Piceatannol has been shown in preclinical studies to have the ability to inhibit or reduce the growth of cancers in various organs such as the brain, breast, lung, colon, cervical, liver, prostate, and skin. However, the bioavailability of Piceatannol is comparatively lower than resveratrol and other stilbenes. Several approaches have been reported in recent years to enhance its bioavailability and biological activity, and clinical trials are required to validate these findings. This review focuses on several aspects of natural stilbene Piceatannol, its chemistry, and its mechanism of action, and its promising therapeutic potential for the prevention and treatment of a wide variety of complex human diseases.

Progress in drug delivery and diagnostic applications of carbon dots: a systematic review.

Carbon dots (CDs), which have particle size of less than 10 nm, are carbon-based nanomaterials that are used in a wide range of applications in the area of novel drug delivery in cancer, ocular diseases, infectious diseases, and brain disorders. CDs are biocompatible, eco-friendly, easy to synthesize, and less toxic with excellent chemical inertness, which makes them very good nanocarrier system to deliver multi-functional drugs effectively. A huge number of researchers worldwide are working on CDs-based drug delivery systems to evaluate their versatility and efficacy in the field of pharmaceuticals. As a result, there is a tremendous increase in our understanding of the physicochemical properties, diagnostic and drug delivery aspects of CDs, which consequently has led us to design and develop CDs-based theranostic system for the treatment of multiple disorders. In this review, we aim to summarize the advances in application of CDs as nanocarrier including gene delivery, vaccine delivery and antiviral delivery, that has been carried out in the last 5 years.

Current perspectives on Vaxinia virus: an immuno-oncolytic vector in cancer therapy.

Viruses are being researched as cutting-edge therapeutic agents in cancer due to their selective oncolytic action against malignancies. Immuno-oncolytic viruses are a potential category of anticancer treatments because they have natural features that allow viruses to efficiently infect, replicate, and destroy cancer cells. Oncolytic viruses may be genetically modified; engineers can use them as a platform to develop additional therapy modalities that overcome the limitations of current treatment approaches. In recent years, researchers have made great strides in the understanding relationship between cancer and the immune system. An increasing corpus of research is functioning on the immunomodulatory functions of oncolytic virus (OVs). Several clinical studies are currently underway to determine the efficacy of these immuno-oncolytic viruses. These studies are exploring the design of these platforms to elicit the desired immune response and to supplement the available immunotherapeutic modalities to render immune-resistant malignancies amenable to treatment. This review will discuss current research and clinical developments on Vaxinia immuno-oncolytic virus.

PROTACs: Promising approach for anticancer therapy.

Proteolysis-targeting chimeras (PROTACs) are being developed as an effective method for degrading cancer-related proteins by modifying the endogenous ubiquitin-proteasome system. To investigate the dynamics between an E3 ligase and target protein, researchers have developed a wide variety of bifunctional PROTACs by combining small molecule ligands. These PROTACs employ numerous ligands, some of which are reversible, some of which are irreversible, some attach to orthosteric sites, while others bind to allosteric sites. Some are agonists, while others are antagonists, and the target protein may be activated in either a positive or negative manner. A variety of targeted ligand approaches can be used to enhance PROTAC properties, including tumor selectivity and drug delivery, and to overcome drug resistance. The processes and behaviors of small molecule-based PROTACs and targeted proteolysis approaches as anticancer therapeutic molecules have been introduced in this mini-review.

Recent advances in cancer therapy using PARP inhibitors.

When DNA repair is inadequate it increases the chances of the genome becoming unstable and it undergoes a malignant mutation. The deficiency of DNA repair PARP proteins may be leveraged for cancer therapy by increasing genomic instability and causing massive DNA damage in cancer cells. DNA repair components are under increased demand in cancer cells because of the continuous replication of DNA. The oncogenic loss of BRCA and an inefficient DNA repair led to cancer cells being dependent on particular DNA repair pathways, like the Poly (ADP-ribose) polymerase pathway. Breast cancer gene 1 and 2 plays a crucial role in DNA repair and genome integrity explaining how BRCA1 and BRCA2 mutations raise the menace of cancer. PARP inhibitors inhibit the base exclusion repair pathway, resulting in the buildup of unrepaired single strand breaks, which cause inflated replication forks in the S phase and subsequently the development of damaging double stranded breaks. Cells having BRCA mutations are unable to repair DNA breaks, leading to apoptosis and eventually death of cancer cells. Numerous indicators, such as a lack of homologous recombination and a high degree of replication pressure, indicate that this therapy will be very effective. Combining PARP inhibitors with chemotherapy, an immune checkpoint inhibitor, and a targeted drug is an effective strategy for combating PARP inhibitors resistance. Several PARP-based combination approaches are in preclinical and clinical development. Various clinical trials are successfully completed and some are undergoing to evaluate the efficacy of these molecules. This review will describe the current views and clinical updates on PARP inhibitors.

Exploring the role of antibiotics and steroids in managing respiratory diseases.

Respiratory diseases (RDs), such as chronic obstructive pulmonary disease, cystic fibrosis, asthma, and pneumonia, are associated with significant morbidity and mortality. Treatment usually consists of antibiotics and steroids. Relevant published literature reviews, studies, and clinical trials were accessed from institutional and electronic databases. The keywords used were respiratory diseases, steroids, antibiotics, and combination of steroids and antibiotics. Selected articles and literature were carefully reviewed. Antibiotics are often prescribed as the standard therapy to manage RDs. Types of causative respiratory pathogens, spectrum of antibiotics activity, route of administration, and course of therapy determine the type of antibiotics that are prescribed. Despite being associated with good clinical outcome, treatment failure and recurrence rate are still high. In addition, antibiotic resistance has been widely reported due to bacterial mutations in response to the use of antibiotics, which render them ineffective. Nevertheless, there has been a growing demand for corticosteroids (CS) and antibiotics to treat a wide variety of diseases, including various airway diseases, due to their immunosuppressive and anti-inflammatory properties. The use of CS is well established and there are different formulations based on the diseases, such as topical administration, tablets, intravenous injections, and inhaled preparations. Both antibiotics and CS possess similar properties in terms of their anti-inflammatory effects, especially regulating cytokine release. Thus, the current review examines and discusses the different applications of antibiotics, CS, and their combination in managing various RDs. Drawbacks of these interventions are also discussed.

Correction: Aljabali, A.A.A.; et al. Albumin Nano-Encapsulation of Piceatannol Enhances Its Anticancer Potential in Colon Cancer via down Regulation of Nuclear p65 and HIF-1α. Cancers 2020, 12, 113.

The authors wish to make the following corrections to this paper [...].

Perspectives and advancements in the design of nanomaterials for targeted cancer theranostics.

Cancer continues to be one of the most challenging diseases to be treated and is one of the leading causes of deaths around the globe. Cancers account for 13% of all deaths each year, with cancer-related mortality expected to rise to 13.1 million by the year 2030. Although, we now have a large library of chemotherapeutic agents, the problem of non-selectivity remains the biggest drawback, as these substances are toxic not only to cancerous cells, but also to other healthy cells in the body. The limitations with chemotherapy and radiation have led to the discovery and development of novel strategies for safe and effective treatment strategies to manage the menace of cancer. Researchers have long justified and have shed light on the emergence of nanotechnology as a potential area for cancer therapy and diagnostics, whereby, nanomaterials are used primarily as nanocarriers or as delivery agents for anticancer drugs due to their tumor targeting properties. Furthermore, nanocarriers loaded with chemotherapeutic agents also overcome biological barriers such as renal and hepatic clearances, thus improving therapeutic efficacy with lowered morbidity. Theranostics, which is the combination of rationally designed nanomaterials with cancer-targeting moieties, along with protective polymers and imaging agents has become one of the core keywords in cancer research. In this review, we have highlighted the potential of various nanomaterials for their application in cancer therapy and imaging, including their current state and clinical prospects. Theranostics has successfully paved a path to a new era of drug design and development, in which nanomaterials and imaging contribute to a large variety of cancer therapies and provide a promising future in the effective management of various cancers. However, in order to meet the therapeutic needs, theranostic nanomaterials must be designed in such a way, that take into account the pharmacokinetic and pharmacodynamics properties of the drug for the development of effective carcinogenic therapy.

Role of the Serine/Threonine Kinase 11 (STK11) or Liver Kinase B1 (LKB1) Gene in Peutz-Jeghers Syndrome.

Peutz-Jeghers syndrome (PJS) is a well-described inherited syndrome, characterized by the development of gastrointestinal polyps and characteristic mucocutaneous freckling. PJS is an autosomal prevailing disease, due to genetic mutation on chromosome 19p, manifested by restricted mucocutaneous melanosis in association with gastrointestinal (GI) polyposis. The gene for PJS has recently been shown to be a serine/threonine kinase, known as LKB1 or STK11, which maps to chromosome subband 19p13.3. This gene has a putative coding region of 1302 bp, divided into nine exons, and acts as a tumor suppressor in the hamartomatous polyps of PJS patients and in the other neoplasms that develop in PJS patients. It is probable that these neoplasms develop from hamartomas, but it remains possible that the LKB1 or STK11 locus plays a role in a different genetic pathway of tumor growth in the cancers of PJS patients. This article focuses on the role of LKB1 or STK11 gene expression in PJS and related cancers.

Hybrid molecules based on 1,3,5-triazine as potential therapeutics: A focused review.

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.

Emerging era of "somes": polymersomes as versatile drug delivery carrier for cancer diagnostics and therapy.

Over the past two decades, polymersomes have been widely investigated for the delivery of diagnostic and therapeutic agents in cancer therapy. Polymersomes are stable polymeric vesicles, which are prepared using amphiphilic block polymers of different molecular weights. The use of high molecular weight amphiphilic copolymers allows for possible manipulation of membrane characteristics, which in turn enhances the efficiency of drug delivery. Polymersomes are more stable in comparison with liposomes and show less toxicity in vivo. Furthermore, their ability to encapsulate both hydrophilic and hydrophobic drugs, significant biocompatibility, robustness, high colloidal stability, and simple methods for ligands conjugation make polymersomes a promising candidate for therapeutic drug delivery in cancer therapy. This review is focused on current development in the application of polymersomes for cancer therapy and diagnosis. Graphical abstract.

Molecular mechanisms of action of naringenin in chronic airway diseases.

Chronic airway inflammatory diseases are characterized by persistent proinflammatory responses in the respiratory tract. Although, several treatment strategies are currently available, lifelong therapy is necessary for most of these diseases. In recent years, phytophenols, namely, flavonoids, derived from fruits and vegetables have been gaining tremendous interest and have been extensively studied due to their low toxicological profile. Naringenin is a bioflavonoid abundantly found in citrus fruits. This substance has shown notable therapeutic potential in various diseases due to its promising diverse biological activities. In this review, we have attempted to review the published studies from the available literature, discussing the molecular level mechanisms of naringenin in different experimental models of airway inflammatory diseases including asthma, chronic obstructive pulmonary disease (COPD), lung cancer, pulmonary fibrosis and cystic fibrosis. Current evidences have proposed that the anti-inflammatory properties of naringenin play a major role in ameliorating inflammatory disease states. In addition, naringenin also possesses several other biological properties. Despite the proposed mechanisms suggesting remarkable therapeutic benefits, the clinical use of naringenin is, however, hampered by its low solubility and bioavailability. Furthermore, this review also discusses on the studies that utilise nanocarriers as a drug delivery system to address the issue of poor solubility.

Albumin Nano-Encapsulation of Piceatannol Enhances Its Anticancer Potential in Colon Cancer Via Downregulation of Nuclear p65 and HIF-1α.

Piceatannol (PIC) is known to have anticancer activity, which has been attributed to its ability to block the proliferation of cancer cells via suppression of the NF-kB signaling pathway. However, its effect on hypoxia-inducible factor (HIF) is not well known in cancer. In this study, PIC was loaded into bovine serum albumin (BSA) by desolvation method as PIC-BSA nanoparticles (NPs). These PIC-BSA nanoparticles were assessed for in vitro cytotoxicity, migration, invasion, and colony formation studies and levels of p65 and HIF-1α. Our results indicate that PIC-BSA NPs were more effective in downregulating the expression of nuclear p65 and HIF-1α in colon cancer cells as compared to free PIC. We also observed a significant reduction in inflammation induced by chemical colitis in mice by PIC-BSA NPs. Furthermore, a significant reduction in tumor size and number of colon tumors was also observed in the murine model of colitis-associated colorectal cancer, when treated with PIC-BSA NPs as compared to free PIC. The overall results indicate that PIC, when formulated as PIC-BSA NPs, enhances its therpautice potential. Our work could prompt further research in using natural anticancer agents as nanoparticels with possiable human clinical trails. This could lead to the development of a new line of safe and effective therapeutics for cancer patients.

Recent advancements in brain tumor targeting using magnetic nanoparticles.

Transport of drugs through the blood-brain barrier to the brain and the toxic effects of drugs on the healthy cells can limit the effectiveness of chemotherapeutic agents. In recent years, magnetic nanoparticles (MNPs) have received much attention as targeted therapeutic and diagnostic systems due to their simplicity, ease of preparation and ability to tailor their properties such as their composition, size, surface morphology, etc. for biomedical applications. MNPs are utilized in drug delivery, radio therapeutics, hyperthermia treatment, gene therapy, biotherapeutics and diagnostic imaging. The present review will address the challenges in brain tumor targeting and discuss the application and recent developments in brain tumor targeting using MNPs.

Implantable systems for drug delivery to the brain.

Most diseases and disorders of the brain require long-term therapy and a constant supply of drugs. Implantable drug-delivery systems provide long-term, sustained drug delivery in the brain. The present review discusses different type of implantable systems such as solid implants, in situ forming implants, in situ forming microparticles, depot formulations, polymeric-lipid implants, sucrose acetate isobutyrate and N-stearoyl L-alanine methyl ester systems for continuous drug delivery into brain for various brain diseases including glioblastomas, medulloblastoma, epilepsy, stroke, schizophrenia and Alzheimer's diseases. Implantable neural probes and microelectrode array systems for brain are also discussed in brief.

Design and development of paclitaxel-loaded bovine serum albumin nanoparticles for brain targeting.

Bovine serum albumin (BSA) nanoparticles loaded with paclitaxel (PTX) were prepared using a desolvation technique. A 32 full factorial design (FFD) was employed to formulate nanoparticles. Nanoparticles were characterized for particle size by photon correlation spectroscopy and surface morphology by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Encapsulation efficiency, zeta potential and particle yield were also determined. Response surface linear modelling (RSLM) was used to predict the optimal formulation. Various models were applied to determine the release mechanism from PTX nanoparticles. The effect of drug-polymer ratio on the release profile of formulations was observed and was applied to determine the suitability of the predicted optimal formulation. A preliminary study to determine the feasibility of targeting the prepared nanoparticles to brain was also carried out using mice as in vivo models.

Flow, compressive, and bioadhesive properties of various blends of poly(ethylene oxide).

BACKGROUND: Poly (ethylene oxide) (PEO) is nonionic, water soluble, and highly hydrophilic polymer with well-established applications in mucoadhesives, water-soluble films, rheology control agents and thickeners, and additives in pharmaceutical products. METHODS: Different powder blends containing PEO in varying proportions were evaluated for their flow, compressive, and bioadhesive properties and subsequently compressed into gastroretentive tablets. Two optimized formulations, on the basis of above-mentioned examinations, were subjected to gamma scintigraphy studies on human volunteers. RESULTS: The values of bulk and tapped densities, Hausner ratio and Carr index, angle of repose, loss on drying, total moisture content, and particle size distribution provided a fine estimation of flowability and compressibility of the powder blends. Further, apart from the routine pharmacopoeial assessments, the evaluation of compressed tablets for their surface pH in both acidic and basic environments nullified the possibility of any irritation to the membrane where it is intended to adhere. The measurement of swelling index and bioadhesive strength of tablets revealed that both the parameters were a direct function of the concentration of PEO in the tablet. The results of gamma scintigraphy indicated a fourfold increase in the gastric retention time of the optimized formulation vis-à-vis control formulation. CONCLUSION: The results indicate that PEO, in a concentration of 10-50% (w/w), can be successfully employed in manufacturing gastroretentive tablets.