Role of Nanoformulations in the Treatment of Lung Cancer.

Lung cancer is the second deadliest disease in the world. A major portion of deaths related to cancer are due to lung cancer in both males and females. Interestingly, unbelievable advances have occurred in recent years through the use of nanotechnology and development in both the diagnosis and treatment of lung cancer. Due to their in vivo stability, the nanotechnology-based pharmacological system gained huge attractiveness, solubility, absorption from the intestine, pharmacological effectiveness, etc. of various anticancer agents. However, this field needs to be utilized more to get maximum results in the treatment of lung cancer, along with wider context medicines. In the present review, authors have tried to concentrate their attention on lung cancer`s difficulties along with the current pharmacological and diagnostic situation, and current advancements in approaches based on nanotechnology for the treatment and diagnosis of lung cancer. While nanotechnology offers these promising avenues for lung cancer diagnosis and treatment, it is important to acknowledge the need for careful evaluation of safety, efficacy, and regulatory approval. With continued research and development, nanotechnology holds tremendous potential to revolutionize the management of lung cancer and improve patient outcomes. The review also highlights the involvement of endocrine systems, especially estrogen in lung cancer proliferation. Some of the recent clinical trials and patents on nanoparticle-based formulations that have applications in the treatment and diagnosis of lung cancer are also discussed.

Cyclodextrin-Based Arsenal for Anti-Cancer Treatments.

Anti-cancer drugs are mostly limited in their use due to poor physicochemical and biopharmaceutical properties. Their lower solubility is the most common hurdle limiting their use upto their potential. In the recent years, the cyclodextrin (CD) complexation have emerged as existing approach to overcome the problem of poor solubility. CD-based nano-technological approaches are safe, stable and showed well in vivo tolerance and greater payload for encapsulation of hydrophobic drugs for the targeted delivery. They are generally chosen due to their ability to get self-assembled to form liposomes, nanoparticles, micelles and nano-sponges etc. This review paper describes a birds-eye view of the various CD-based nano-technological approaches applied for the delivery of anti-cancer moieties to the desired target such as CD based liposomes, niosomes, niosoponges, micelles, nanoparticles, monoclonal antibody, magnetic nanoparticles, small interfering RNA, nanorods, miscellaneous formulation of anti-cancer drugs containing CD. Moreover, the author also summarizes the various shortcomings of such a system and their way ahead.

Multifunctional Patented Nanotherapeutics for Cancer Intervention: 2010- Onwards.

Even today, cancer is one of the prominent leading causes of death worldwide. However, there are a couple of treatment options available for management, but the adverse effects are more prominent as compared to therapeutic effects. Therefore, there is a need to design some midway that may help to bypass the negative effects or lower their severity. Nanotechnology has addressed many issues, still many miles are needed to cover before reaching the center stage. The developed nanoformulations can target distant organs owing to their multifunctionality and targeting potential. Stimuli-responsive nanomedicine is one of the most exploited formulations. They can encapsulate and release the drugs for a higher period. However, they release a burst mechanism. The other nanoformulations contain dendrimers, micelles, and lipid-based nano-formulations that have been developed and evaluated for their efficacy in cancer treatment. This review paper highlights some significant patents granted/applied in various patent offices around the globe to treat cancer using the nanotechnology. The Google Patent, United States Patent and Trademark Office (USPTO), Escapenet, and many others were used as the search engine for patent search, and data were collected and analyzed. They used these patented technologies for diagnostic and treatment options, enhancing the absorption, distribution, metabolism, and excretion (ADME) profile of therapeutic molecules.

Design and Molecular Docking Studies of N-Mannich Base Derivatives of Primaquine Bearing Isatin on the Targets involved in the Pathophysiology of Cerebral Malaria.

BACKGROUND: Malaria is considered one of the life-threatening mosquito-borne infectious diseases responsible for approximately more than 4,00,000 deaths every year all over the world. Plasmodium falciparum and Plasmodium vivax are widespread species, but infections caused by the former are of great concern. OBJECTIVE: Among the various forms of infections associated with Plasmodium falciparum, cerebral malaria (CM) is the most severe neurological complication, accounting for almost 13% of all malariarelated mortality. The development of effective therapeutics is urgently needed to overcome the fatality of this dreadful disease. METHODS: The present work attempted to design and virtually screen a chemical library of 75 molecules (N-Mannich base derivatives of primaquine bearing isatin moiety as heterocyclic) by molecular docking studies against anti-malarial target proteins-Cystein Protease Falcipain-2; Dipeptidyl Aminopeptidase- 1; Dipeptidyl Aminopeptidase-3 and Glycogen synthase Kinase-3ß receptors, for evaluating their anti-malarial potential. Among all studied anti-malarial target receptors, the designed molecules showed an overall higher affinity for Dipeptidyl Aminopeptidase-3. Furthermore, the molecules were analyzed for binding affinity and drug-like properties using Lipinski rules, and 30 best hits were shortlisted and analyzed for the pharmacokinetic profile. RESULTS: Two of these hits were found to be more toxic than primaquine, hence were omitted in further analysis. Later, these 28 hits were docked against two target proteins, (a) Plasmodium falciparum erythrocyte membrane protein-1 and (b) Intracellular adhesion molecule-1, to determine their efficiency against cerebral malaria, and the results were recorded. Analysis of docking results led to the identification of the 8 studied molecules as lead molecules which were selected for chemical synthesis, in vivo studies, and further preclinical evaluation. CONCLUSION: The molecule DSR 11 was predicted as the most appropriate lead molecule for anti-CM activity in the present investigation apart from the other seven molecules (DSR4, DSR26, DSR38, DSR40, DSR49, DSR56, and DSR70).

Nanocapsules: An Emerging Drug Delivery System.

BACKGROUND: Controlled drug release and site-specific delivery of drugs make nanocapsules the most approbative drug delivery system for various kinds of drugs, bioactive, protein, and peptide compounds. Nanocapsules (NCs) are spherical shape microscopic shells consisting of a core (solid or liquid) in which the drug is positioned in a cavity enclosed by a distinctive polymeric membrane. OBJECTIVES: The main objective of the present patent study is to elaborate on various formulation techniques and methods of nanocapsules (NCs). The review also spotlights various biomedical applications as well as on the patents of NCs to date. METHODS: The review was extracted from the searches performed using various search engines such as PubMed, Google Patents, Medline, Google Scholars, etc. In order to emphasize the importance of NCs, some published patents of NCs have also been reported in the review. RESULTS: NCs are tiny magical shells having incredible reproducibility. Various techniques can be used to formulate NCs. The pharmaceutical performance of the formulated NCs can be judged by evaluating their shape, size, entrapment efficiency, loading capacity, etc., using different analytical techniques. Their main applications are found in the field of agrochemicals, genetic manipulation, cosmetics, hygiene items, strategic distribution of drugs to tumors, nanocapsule bandages to combat infection, and radiotherapy. CONCLUSION: In the present review, our team made a deliberate effort to summarize the recent advances in the field of NCs and focus on new patents related to the implementation of NCs delivery systems in the area of some life-threatening disorders like diabetes, cancer, and cardiovascular diseases.

Nanocrystals: A Deep Insight into Formulation Aspects, Stabilization Strategies, and Biomedical Applications.

BACKGROUND: Drugs with poor solubility exhibit hurdles in their formulation due to poor dissolution and low bioavailability. Nanocrystallization is a great technique for incorporating poorly soluble drugs and is associated with many benefits. OBJECTIVE: The objective of the present review is to discuss formulation techniques for the generation of Nanocrystals (NCs) and illustrate the various advantages of NCs. It also explains commonly used stabilizers and guidelines for their safe use for enhancing NCs and provides a deep insight into various biomedical applications of NCs. METHODS: The review was extracted from the study carried out in the general literature to emphasize the importance of NCs in various formulations. RESULTS: NCs are a widely accepted approach to enhancing drug solubility. There are so many marketed products of nanocrystal drug formulations that are being used to treat life-threatening disorders. Two techniques can be used to formulate NCs, i.e., the bottom-up method and the top-down method. Their main biomedical applications are found in oral, parenteral, pulmonary, ocular, dermal, and mucosal formulations. CONCLUSION: In the present review, different formulation methods of NCs have been discussed in detail, followed by explaining the advantages and various targeted drug delivery systems covered by NCs formulations. The development of NCs-based formulation avoids the limitations of other systems used for targeted drug delivery.

An Update on Recent Advances for the Treatment of Cerebral Malaria.

Among all the parasitic diseases in humans, malaria is the most significant and malicious one. The widespread species are Plasmodium falciparum and Plasmodium vivax, but the infection caused by the former is the deadliest. According to the November 2018 report of the World Health Organization (WHO), a total of 219 million cases of malaria were reported globally in 2017, which led to an estimated 435,000 deaths. Mortality due to malaria is estimated at 1.5 - 2.7 million deaths each year. Among all the complications associated with Plasmodium falciparum infection, cerebral malaria (CM) is the most fretful, accounting for almost 13% of all malaria-related deaths. CM is a medical emergency that requires immediate clinical testing and treatment. A compromised microcirculation, with sequestration of parasitized erythrocytes, is central in the disease pathology. No effective therapeutic agents are available yet for the treatment of CM, and therefore, potential interventions are needed to be developed urgently. The currently available anti-malarial drugs lack lipophilicity and are thus not able to reach the brain tissues. Therefore, safe, cost-effective agents with improved lipophilicity possessing the potential to target brain tissues are needed to be searched in order to fight CM worldwide. The aim of present review is to systematically revise the published research work available concerning the development and evaluation of some potential drug targets in the management of CM.

Exploration of therapeutic applicability and different signaling mechanism of various phytopharmacological agents for treatment of breast cancer.

BACKGROUND: Cancer is one of the most dreaded diseases characterized by uncontrolled proliferation of abnormal cells that occurs due to impairment of cell division and apoptosis process. Cancer is categorized into several types on the basis of affected organs and breast cancer (BC) is the most predominant cause of mortality among women. Although, several synthetic and semi-synthetic therapies have been developed for the treatment of BC but they exhibit numerous serious adverse effects therefore; pharmacological agents with fewer/no side effects need to be explored. Plants and phytoconstituents perhaps fulfill the aforementioned requirement and could serve as a potential and alternative therapy for BC treatment. The ongoing biomedical research, clinical trials and number of patents granted have further boosted the acceptance of the plants and plant-derived constituents in the effective treatment of BC. PURPOSE OF STUDY: Various treatment strategies such as checkpoint inhibitors, targeting micro RNA, apoptotic pathway, BRCA-1 gene, P53 protein, P13K/Akt/mTOR pathway, notch signaling pathway, hedgehog/gli-1 signaling pathway, poly-ADP ribose polymerase inhibitors, mitogen-activated protein kinase inhibitors etc. are available for BC. In addition to these synthetic and semi-synthetic drug therapies, several natural constituents such as alkaloids, sesquiterpenes, polyphenols, flavonoids and diterpenoids from medicinal plants, vegetables and fruits are reported to possess promising anti-cancer activity. The purpose of the present review is to highlight the various signaling pathways through which plants/herbs show the anti-cancer potential especially against the BC. STUDY DESIGN: The literature for the present study was collected from various databases such as Pubmed, Scopus, Chemical Abstracts, Medicinal and aromatic plant abstracts, Web of Science etc. The different patent databases were also reviewed for the anti-cancer (BC) potential of the particular herbs/plants and their formulations. RESULT AND CONCLUSION: In this review, we have discussed the number of plants along with their patents of different herbal formulations which are being used for the treatment of BC and other types of cancers. We have also delineated the different signaling mechanisms through which they inhibit the growth of BC cells. In nutshell, we can conclude that large numbers of herbs or their extracts are reported for the treatment of BC. But still, there is further need for research in-depth to translate the use of natural products clinically BC treatment.

Radiopharmaceuticals: An insight into the latest advances in medical uses and regulatory perspectives.

The growing armamentarium of potential radioisotopes and increased demand for radiopharmaceuticals (RPs) have catapulted their biomedical applications on a trajectory of higher growth in the modern healthcare establishment. Nuclear medicine technology is now regarded as an essential tool for diagnosis, palliation, therapy, and theranostic applications. The associated radiation safety issues need to be emphasized in the form of adequate regulatory action to warrant their safe and effective use. The RPs attracts considerable attention from both pharmaceutical and nuclear regulators due to their constituent pharmaceutical and radioactive components. So, a critical examination of applications of RPs, the latest advances in their development, and the existing regulatory guidelines for RPs have been carried out. This review presents a brief overview of RPs and recent studies on their diagnostic, therapeutic, and theranostic applications. Comprehensive comparative information on regulatory perspectives of RPs in major pharmaceutical jurisdictions such as the United States (US), the European Union (EU), and India reveals ambiguities and heterogeneity. The present studies discuss the importance of RPs in the current healthcare domain, their recent applications, and strive to intensify the concern for an ambient and harmonized regulatory setup.

An Overview of Recent Patents and Patented Technology Platforms Based on Co-Processed Excipients.

BACKGROUND: There is no single-component excipient that fulfills all the requisite performance to allow an active pharmaceutical ingredient to be formulated into a specific dosage form. Co-processing is a novel concept that incorporates a combination of two or more excipients, that is advantageous and cannot be achieved using a physical admixture. OBJECTIVE: This review provides an overview of co-processed excipients, recent patents granted and filed in this field and the commercial patented technology platforms based on these excipients. METHODS: Various online patent databases were used for collecting the information on recent patents and patented co-processed excipient technologies. The recent patents such as single-step coprocessing by dry coating, novel co-processed excipients for oily drugs and novel silica-coated compositions have been discussed. RESULTS: Co-processed excipients are evolving as a current and future trend of excipient technology in pharmaceutical manufacturing, which is evident by the increasing number of patents based on these excipients. Among various techniques, the maximum number of patents is based on the spray drying technique. CONCLUSION: In this work, the authors have focussed on recent patents and commercial technologies on co-processed excipient. A better understanding of this will help researchers and pharmaceutical industries to select the appropriate platform, or to develop new innovative co-processed excipients with improved tableting characteristics.

An Overview of the Recent Developments and Patents in the Field of Pharmaceutical Nanotechnology.

BACKGROUND: Compared to traditional dosage methods, the Novel Drug Delivery Systems (NDDS) provide various advantages. In the last few years, the interest shifted to works focused on the novel drug delivery methods for small and large molecular drug carriers utilizing particulate drug delivery systems as well. It is evident from the last decade as observed in increased number of patents in this field that the technology has evolved tremendously. OBJECTIVE: Drug carriers utilized by this novel technology include liposomes, dendrimers, polymeric nanoparticles, magnetic nanoparticles, solid lipid nanoparticles, and carbon nanomaterials. Various forms of polymers have been used in the production of nanocarriers. METHODS: Nanocarriers are colloidal systems varying in size from 10 to 1000 nm. This technology is now used to identify, manage and monitor numerous diseases and physical methods to alter and enhance the pharmacokinetic and pharmacodynamic properties of specific types of drug molecules. RESULTS: Nanoparticles can be formulated by a number of techniques including ionic gelation, crosslinking, coacervation/precipitation, nanoprecipitation, spray drying, emulsion- droplet coalescence, nano sonication techniques, etc. Several methods are used with which these nanoparticles can be characterized. These methods include nuclear magnetic resonance, optical microscopy, atomic force microscopy, photon correlation spectroscopy and electron microscopy, surface charge, in-vitro drug release, etc. Conclusion: In the present review, the authors have tried to summarize recent advances in the field of pharmaceutical nanotechnology and also focused on the application and new patents in the area related to NDDS.

Nanoemulsion: A Novel Drug Delivery Approach for Enhancement of Bioavailability.

BACKGROUND: Poor bioavailability and solubility of drugs in aqueous phase are the most important problems of newly developed chemical entities that can be improved by nanoemulsion. OBJECTIVES: BCS class II and IV which are poorly soluble in water demonstrate various problems in conventional dosage forms. For the improvement of solubility, bioavailability and getting the best therapeutic effect of poorly soluble drugs nanoemulsion is the best solution. METHODS: Nanoemulsion are thermodynamically unstable isotropic system with droplet size 1-100 nm in which two immiscible fluids are combined together to form one phase by using an emulsifying agent. Nanoemulsion can be designed to promote the bioavailability of API by trapping them inside. RESULTS: Nanoemulsion can be developed in many dosage forms such as oral, parenteral, topical, ophthalmic dosage form in large scale using common operation at a very low cost. Large range of lipophilic drugs can be easily incorporated in nanoemulsion. CONCLUSION: In this review, attention is focused on the type of nanoemulsions, their advantages over other dosage form, method for their preparation, characterization, applications and patents in various fields.

Anti-DENV and Anti-Dengue Vector Activity of Some Heterocyclic Scaffolds.

Dengue is a major health threat related to arbovirus and is endemic in more than 100 countries with an annual estimated above 390 million incidences of infection all around the world. During the period 1996-2015, a considerable increase in the number of dengue cases (more than 500%) was reported in India. Information about dengue disease burden, its prevalence, incidence and geographic distribution is critical in planning appropriate control measures against dengue fever. Till date, no specific treatment for dengue fever is available in any system of medicine, which can be accepted globally. Therefore, safe, cost-effective, and efficacious agents possessing anti-viral potential against dengue virus are needed to be searched in order to fight the dengue infection globally. The aim of the present review is to systematically revise the published research work available concerning the development and evaluation of some heterocyclic scaffolds in the management of dengue.

Three-dimensional Quantitative Structure-activity Relationship (3DQSAR) and Molecular Docking Study of 2-((pyridin-3-yloxy)methyl) Piperazines as α7 Nicotinic Acetylcholine Receptor Modulators for the Treatment of Inflammatory Disorders.

BACKGROUND & OBJECTIVE: Comparative molecular field analysis (CoMFA) of 27 analogues of 2-((pyridin-3-yloxy)methyl)piperazine derivatives was carried out using software Tripos SYBYL X. Optimal r2 (0.854) and q2 (0.541) values were obtained for the developed 3D-QSAR model. The contour plots obtained from CoMFA analysis have shown 13.84% steric contribution and 66.14% electrostatic contribution towards an anti-inflammatory activity. METHODS: The homology model of the receptor protein, α7 nicotinic acetylcholine, was generated in SWISS MODELLER using auto template mode and was analysed for the quality using Procheck, QMEAN Z-score, Anolea and GROMOS plots. The QMEAN score for the model was observed to be - 3.862. The generated model of alpha 7 nicotinic acetylcholine receptor was used for docking study of 27 piperazine analogues using Auto-Dock 4.2.5.1. RESULTS: The dock score obtained from docking analysis was then correlated with experimental pIC50 values for in-silico validation of the developed CoMFA model and a good correlation was obtained with correlation coefficient (r2) value of -0.7378. CONCLUSION: The present investigation suggests an optimal 3D-QSAR with CoMFA model for further evaluating new chemical entities based on piperazine skeleton.

Nanosponges -A Promising Novel Drug Delivery System.

BACKGROUND: Pharmacokinetic issues and poor solubility in water are the most important concerns of numerous recently developed chemical entities. OBJECTIVE: The drugs which are poorly soluble in water demonstrate numerous formulating troubles in conventional dosage forms and the low bio-availability is the critical problem linked with it. A nanosponge is an emerging technology which can overcome these problems and precisely control the release rates of controlled drug delivery. METHOD: Nanosponges are tiny mesh-like structures with a size less than 1µm. Due to their porous structure and small size; they can easily bind to drugs which are poorly-soluble leading to better bioavailability and solubility of such drugs. A broad range of drugs including both hydrophilic and lipophilic can be easily loaded into nanosponges. RESULTS: These minute sponges can circulate until they reach the definite target site, attach themselves to the surface and initiate the discharge of drugs in a predictable and controlled way. Nanosponges are solid in character and can be developed in various dosage forms such as parenteral, topical, oral or inhalational. Nanosponge drug delivery system has been developed as one of the most capable aspects in the field of pharmaceuticals. CONCLUSION: In this review, an attempt has been made to highlight the advantages, characteristics, application, methods of preparation and characterization of nanosponges along with the recent patents on nanosponges.