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Protein kinases, a class of enzymes that govern various biological phenomena at a cellular level, are responsible for signal transduction in cells that regulate cellular proliferation, differentiation, and growth. Protein kinase enzyme mutation results in abnormal cell division leading to a pathological condition like cancer. Tyrosine kinase (TK) inhibitors, which helps as a potential drug candidate for the treatment of cancer, are continuously being developed. Majority of these drug candidates are being administered as conventional oral dosage form, which provides limited safety and efficacy due to non-specific delivery and uncontrolled biodistribution resulting into the adverse effects. A controlled drug delivery approach for the delivery of TK inhibitors may be a potential strategy with significant safety and efficacy profile. Novel drug delivery strategies provide target-specific drug delivery, improved pharmacokinetic behaviour, and sustained release leading to lower doses and dosing frequency with significantly reduced side effects. Along with basic aspects of tyrosine kinase, this review discusses various aspects related to the application of tyrosine kinase inhibitors in clinical oncological setting. Furthermore, the limitations/challenges and formulation advancements related to this class of candidates particularly for cancer management have been reviewed. It is expected that innovations in drug delivery approaches for TK inhibitors using novel techniques will surely provide a new insights for improved cancer treatment and patients' life quality.

Background: Pharmacovigilance (PV) deals with the detection, collection, assessment, understanding, and prevention of adverse effects associated with drugs. The objective of PV is to ensure the safety of the medicines and patients by monitoring and reporting all adverse drug reactions (ADRs) associated with prescribed medicine usage. Findings have indicated that about 0.2-24% of hospitalization cases are due to ADRs, of which 3.7% of patients have lethal ADRs. The reasons include the number of prescribed drugs, an increased number of new medicines in the market, an inadequate PV system for ADR monitoring, and a need for more awareness and knowledge about ADR reporting. Severe ADRs lead to enhanced hospital stays, increased treatment costs, risk of death, and many medical and economic consequences. Therefore, ADR reporting at its first instance is essential to avoid further harmful effects of the prescribed drugs. In India, the rate of ADR reporting is less than 1%, whereas worldwide, it is 5% due to a need for more awareness about PV and ADR monitoring among healthcare providers and patients. Aim: The main objective of this review is to highlight the current scenario and possible futuristic ways of ADR reporting methods in rural areas of India. Method: We have searched the literature using PubMed, Google scholar, Indian citation index to retrieve the resources related to ADR monitoring and reporting in India's urban and rural areas. Results: Spontaneous reporting is the most commonly used PV method to report ADRs in India's urban and rural areas. Evidence revealed that no effective ADR reporting mechanisms developed in rural areas causing underreporting of ADR, thus increasing the threat to the rural population. Conclusion: Hence, PV and ADR reporting awareness among healthcare professionals and patients, telecommunication, telemedicine, use of social media and electronic medical records, and artificial intelligence are the potential approaches for prevention, monitoring, and reporting of ADR in rural areas.

The coronavirus disease (COVID-19) has relentlessly spread all over the world even after the advent of vaccines. It demands management, treatment, and prevention as well with utmost safety and effectiveness. It is well researched that herbal medicines or natural products have shown promising outcomes to strengthen immunity with antiviral potential against SARS-COV-2.Our objective is to provide a comprehensive insight into the preventive and therapeutic effects of herbal medicines and products (Ayurvedic) for pre-and post-COVID manifestations.The database used in the text is collected and compiled from Scopus, PubMed, Nature, Elsevier, Web of Science, bioRxiv, medRxiv, American Chemical Society, and clinicaltrials.gov up to January 2022. Articles from non-academic sources such as websites and news were also retrieved. Exploration of the studies was executed to recognize supplementary publications of research studies and systematic reviews. The keywords, such as "SARS-COV-2, coronavirus, COVID-19, herbal drugs, immunity, herbal immunomodulators, infection, herbal antiviral drugs, and WHO recommendation" were thoroughly searched. Chemical structures were drawn using the software Chemdraw Professional 15.0.0.160 (PerkinElmer Informatics, Inc.).A plethora of literature supports that the use of herbal regimens not only strengthen immunity but can also treat SARS-COV-2 infection with minimal side effects. This review summarizes the mechanistic insights into herbal therapy engaging interferons and antibodies to boost the response against SARS-COV-2 infection, several clinical trials, and in silico studies (computational approaches) on selected natural products including, Ashwagandha, Guduchi, Yashtimadhu, Tulsi, etc. as preventive and therapeutic measures against COVID. We have also emphasized the exploitation of herbal medicine-based pharmaceutical products along with perspectives for unseen upcoming alike diseases.According to the current state of art and cutting-edge research on herbal medicines have showed a significant promise as modern COVID tools. Since vaccination cannot be purported as a long-term cure for viral infections, herbal/natural medicines can only be considered a viable alternative to current remedies, as conceived from our collected data to unroot recurring viral infections.

Introduction: Solid lipid nanoparticles (SLNs) are solid core lipid nanocarriers, which can hold both hydrophilic and hydrophobic drugs. They can be made up of biocompatible ingredients and therefore are one of the preferred choices for drug delivery. Surface modifications of SLNs may further provide unique features to them like mucoadhesiveness or targeting capability.Areas covered: In this review, the authors have covered areas from the basic introduction of SLNs to its applications in controlled drug delivery. More specifically, the authors have covered patents disclosed related to the SLNs for the period 2014-2019; however, a summary of patents of 2008-2013 is also included.Expert opinion: SLNs have been explored for development of compositions/formulations with improved therapeutics or cosmetic applications or for nutraceutical applications. Targeted SLNs compositions have been patented as evidenced from the literature; however, not such types of enough SLNs formulations have been claimed for the same.

Reverse engineering or deformulation is a known process for generic product development and is widely used by the pharmaceutical industry for regulatory purpose. In order to achieve a generic product having all the essential features described in Q1/Q2/Q3 ICH guidelines, a systematic, well-planned and skilled process is applied to identify the API, excipients and physicochemical characteristics of the innovator product. Apart from this, reverse engineering is applied on stability testing and identification of manufacturing defects. Here, we summarised to answer few questions like why it is required, how it is performed, what are common analytical techniques and method involved in the reverse engineering of tablet, capsule, ophthalmic preparation, depot and herbal formulations. This chapter deals with the review of the literature on this demanding topic with a comprehensive discussion on case studies.

The clinical efficacy of chemotherapy of cancer cells is limited due to many factors, including the undesired distribution of cytotoxic drugs to healthy vital cells, low bioavailability in the tumor microenvironment, and the development of multidrug resistance (MDR). Biedler and Riehm reported the concept of MDR in chemotherapy way back in the 1970s. Briefly, MDR in cancer cells can be defined as the resistance of cells to any anticancer agent accompanied by other chemotherapeutic drugs, which possess different structures and functional moieties, or it can also be defined as a condition of resilience against structurally and functionally dissimilar drugs.

Background: Nanopharmaceuticals serve as emerging forms of modern medicines, which include nanomedicines, nanosimilars, nanotheranostics, nanodevices, and many more. In the last two decades, a large number of nano-based products have reached the market and are being used clinically. Objectives: Unlike conventional pharmaceutical products, nanopharmaceuticals behave differently both in vitro and in vivo, and therefore, the development of their generic versions needs special attention to replicate the similar drug release pattern leading to an identical therapeutic outcome. Further, drug-device combinations and 3D products are the latest advancements in precision medicine delivery and development. Methods: The regulatory guidelines for these products are being framed at many stages by various regulatory agencies like USFDA/EMA and still are in infancy at the moment if we look at wider perspectives and applications of nanomedicine. Results: For a formulation scientist, it is much needed that well-explained and directive guidelines should be made available before leading to the development of the generic versions of these nano-cargos. Conclusion: Here, in this review, we have summarized the silent features of the regulatory perspectives related to nanotechnology based next generation therapeutics and diagnostics.

Pharmacovigilance (PV) deals with the detection, collection, assessment, understanding and prevention of adverse effects associated with the drugs. The objective of PV is to ensure safety of the medicines and patients by monitoring and reporting of all adverse drug reactions (ADRs) associated with prescribed medicine usage. Findings have indicated that about 0.2-24% of hospitalization cases are due to ADRs out of which 3.7% of patients have lethal ADRs. The reasons includes number of prescribing drugs, increased new drugs in the market, and inadequate PV system for ADRs monitoring, lack of awareness and knowledge about ADRs reporting. Serious ADRs leads to enhanced hospital stay, increased treatment cost, risk of death, and many medical and economic consequences. Therefore, ADR reporting at its first instance is important to avoid further harmful effects of the prescribed drugs. In India, the rate of ADR reporting is less than 1% whereas worldwide it is 5% due to lack of awareness about PV and ADR monitoring among healthcare providers and patients. Spontaneous reporting is the most commonly used PV method to report ADRs in both urban and rural areas of India. Evidences revealed that there is not any effective ADR reporting mechanisms developed in rural areas causing underreporting of ADR thus increasing threat to the rural population. Hence, PV and ADR reporting awareness among healthcare professionals and patients, telecommunication, telemedicine, use of social media and electronic medical records, and artificial intelligence are the potential approaches for prevention, monitoring and reporting of ADR in rural areas.

Hepatocellular carcinoma (HCC) is a foremost type of cancer problem in which asialoglycoprotein receptors are overexpressed. In this study, asialoglycoprotein receptor–targeted nanoformulation (galactose-conjugated TPGS micelles) loaded with docetaxel (DTX) was developed to achieve its site-specific delivery for HCC therapy. The pharmaceutical characteristics like shape morphology, average particle size and zeta potential, drug entrapment efficiency, and in vitro release kinetics of developed system were evaluated. DTX-loaded galactosylated TPGS (DTX-TPGS-Gal) micelles and TPGS micelles (DTX-TPGS) were having 58.76 ± 1.82% and 54.76 ± 1.42% entrapment of the DTX, respectively. In vitro drug release behavior from micelles was controlled release. Cytotoxicitiy (IC50) of DTX-TPGS-Gal formulation on HepG2 cell lines was significantly (p ≤ 0.01) lower (6.3 ± 0.86 μg/ml) than DTX-TPGS (9.06 ± 0.82 μg/ml) and plain DTX (16.06 ± 0.98 μg/ml) indicating higher efficacy of targeted formulation. Further, in vivo biodistribution studies in animal model showed maximum drug accumulation at target site, i.e., the liver in the case of DTX-TPGS-Gal as compared with non-targeted one. It is concluded from the findings that TPGS-Gal micelles can be utilized for targeted drug delivery of cytotoxic drugs towards HCC with minimized side effects.

Nanotheranostics, an approach of combining both diagnosis and therapy, is one of the latest advances in cancer therapy particularly. Nanocarriers designed and derived from inorganic materials such as like gold nanoparticles, silica nanoparticles, magnetic nanoparticles and carbon nanotubes have been explored for tremendous applications in this area. Similarly, nanoparticles composed of some organic material alone or in combination with inorganic nano-cargos have been developed pre-clinically and possess excellent features desired. Photothermal therapy, MRI, simultaneous imaging and delivery, and combination chemotherapy with a diagnosis are a few of the known methods exploring cancer therapy and detection at organ/tissue/molecular/sub-cellular level. This review comprises an overview of the recent reports meant for nano theranostics purposes. Targeted cancer nanotheranostics have been included for understating tumor micro-environment or cell-specific targeting approach employed. A brief account of various strategies is also included for the readers highlighting the mechanism of cancer therapy.

Background Transdermal drug delivery represents an extremely attractive and innovative route across the skin owing to the possibility for achieving systemic effect of drugs. The present scenario demands a special focus on developing safe medicine with minimized toxic adverse effects related to most of the pharmacologically active agents. Transdermal drug delivery would be a focal paradigm which provides patient convenience, first-pass hepatic metabolism avoidance, local targeting and reduction in toxic effect related to various categories of drugs like, analgesics, antiinflammatory, antibiotics, antiviral, anaesthetic, anticancer etc. Even this route has challenges due to highly organized structure of skin which acts as a main barrier to penetration of drug via the skin. Method Several alternative possible strategies are available which overcome these barriers, including use of penetration enhancer, eletroporation, iontophoresis and various nanotechnologically developed nanocarrier systems. The latest one includes employing liposome, dendrimers, nanoparticles, ethosome, carbon nanotube and many more to avoid associated limitations of conventional formulations. Numerous transdermal products such as Estrasorb, Diractin, VivaGel®, Daytrana®, Aczone, Sileryst® are available in the market having a novel strategy to achieve higher penetration of drugs. This encourages formulation fraternity to develop structurally deformable and stable nanocarriers as an alternative approach for controlled and reliable drug delivery across the skin barrier. Discussion In this review, we will discuss nanocarriers mediated approaches that come-up with the solutions to the different challenges towards transdermal drug delivery, its clinical importance and latest insight to research in it. Conclusion The reports presented in this review confirm the wide application of nanocarriers for transdermal delivery of drug/gene.

This chapter deals with the miscellaneous approaches of chemoprevention including synthetic chemicals, vitamins, NSAIDs, antioxidants, etc. Role of silver nanoparticles and selenium nanoparticles is also described in chemoprevention. A section on combination therapies using both phytopharmaceuticals and synthetic anticancer drugs is also added. The reports on simultaneous use of diagnostic agent with chemopreventive agents are further described in the chapter.

This chapter deals with the information on natural nutrients used for chemoprevention. Phytochemicals such as polyphenols (curcumin), flavonoids (anthocyanidins, flavonols, flavones, flavanones, catechins (Flavan-3-ols), and isoflavones), phytoalexin (resveratrol), and kaempferol are discussed in detail with their mechanisms as chemopreventive agents. Various signaling pathways or factors which are reported in the literature have been described. Various properties of nutrients and phytochemicals under investigation as chemopreventive agents have also been elaborated.

This chapter describes the basic introduction of carcinogenesis and chemoprevention. A section presented highlights on the natural resources of chemopreventive agents. The different mechanism pathways of chemoprevention are also included in this chapter. Pharmaceutical need for the development of safe and more efficacious chemoprevention strategies is also discussed. A brief account on nanotechnology-based delivery of chemopreventive agents is discussed.

This chapter includes basics of targeted drug delivery and their advantages and disadvantages. The different strategies like drug conjugates and ligand anchored nanocarriers for targeted delivery of phytochemicals are also discussed. The next section demonstrates stimuli-responsive targeting such as pH-sensitive delivery and temperature responsive targeting of chemopreventive agents.

Phytoconstituents have some limitations like poor bioavailability, stability issues and hence limited therapeutic efficacy upon administration. Such issues can be warranted using the controlled delivery of these molecules with the help of novel drug delivery systems especially nano-sized carrier systems. A wide range of biomaterial and their suitable engineering into a nanocarrier navigate them to the target site. In this chapter, we have covered the aspects of various nanosystems that are being used for the delivery of chemopreventive agents like polymeric nanoparticles, solid lipid nanoparticles, vesicular systems (liposomes and phytosomes), metallic nanoparticles (iron, gold, silver, and silica), nanocapsules, and hybrid nanosystems.

Herbal nanomedicine is one of the fastest growing research areas. The regained interests in the cancer treatment and chemoprevention using herbal chemicals have turned the coin with the help of nanotechnology. Regulatory concerns related to nanotechnology and herbal formulations are being used at present to assess the essential characteristics of herbal nanomedicines. In this chapter, we have summarized all the key points and progress of the herbal nanomedicine including discussion on quality control of nanoparticles, toxicity consideration of nanomedicines, and assessment and importance of efficacy, safety, and quality control of herbal medicines.

Rheumatoid arthritis is a severe autoimmune disorder, related to joints. It is associated with serious cartilage destruction. This causes disability and reduces the excellence of life. Numerous treatments are existed to combat this disease, however, they are not very efficient and possess severe side effects, higher doses, and frequent administration. Therefore, newer therapies are developed to overcome all these limitations. These include different monoclonal antibodies, immunoglobulins, small molecules used for immunotherapy and transgenes for gene therapy. One of the main goals of these new generation therapeutics is to address the underlying distressing biological processes by specifically targeting the causative agents with fewer systemic side effects and greater patient console. It is very fortuitous that loads of progressive investigations are going on in this field and many of them have entered into the successful clinical trial. But till date, a limited molecule has got FDA clearance and entered the market for treating this devastating disease. This review highlights the overview of conventional therapy and advancements in newer therapeutics including immunotherapy and gene therapy for rheumatoid arthritis. Further, different novel techniques for the delivery of these therapeutics of active and passive targeting are also described.

Cancer is a leading cause of human death throughout the world. The lack of specificity associated with conventional anti-cancer therapeutics leads to several side effects in addition. Cancer initiation and progression involve complex and multi carcinogenesis processes along with diverse cellular physiological system activities like cell signaling and apoptosis. An erratic microenvironment and drug resistance mechanism of cancer cells further causes failure of the most conventional chemotherapy regimen. Such limitations of the conventional cancer therapy advocate well engineered and smart therapeutics for cancer treatment. An ideal cancer treatment needs a customized and specialized drug delivery technology, which is capable to eradicate even a last cancer cell that may be responsible for the relapse of disease. Targeted nanocarriers (NCs) navigate the loaded therapeutics towards the specific site of action with the reduced adverse effects on the healthy cells. This review presents an overview of various molecular mechanisms and cellular alterations associated with cancer cell development and how targeted formulations can be designed for cancer therapy. A brief focuses on the applications of nanotechnology to exploit these mechanisms and molecular ports for the development of a novel targeted formulation for cancer treatment has also been discussed.

Chitosan, a cationic polymer, is very well utilized for numerous applications, including drug delivery. This polymer has been routinely explored for drug delivery through ocular route, because of its charge-based character and mucoadhesive properties. Chitosan and its different derivatives have been explored for controlled delivery of drugs, proteins, and peptides. Because of its well-established safety issue as reported in the literature for ocular delivery purposes, it has become the choice of the formulation development scientist either alone or in combination with other polymers/lipids, etc. This chapter deals with progress and recent reports published for the readers who are interested for polysaccharides-based ocular drug delivery and chitosan as an alternative option for the same.