Current Pharmaceutical Design - Volume 26, Issue 42, 2020

Breast cancer (BC) is the commonest cause of cancer deaths among Women. It is known to be caused due to mutations in certain receptors, viz. estrogens or progesterones. The most frequently used conventional treatment strategies against BC include chemotherapy, radiation therapy, and partial or entire mastectomy, however, these strategies are often associated with multiple adverse effects, thus reducing patient compliance. Advancement of nanotechnology in the medical application has been made to enhance the therapeutic effectiveness with a significant reduction in the unintended side-effects associated with incorporated anticancer drugs against cancer. The surface engineering technology of the nanocarriers is more pronounced in delivering the therapeutics specifically to target cells. Consequently, folic acid, a small molecular ligand for the folate receptor overexpressed cells, has shown immense response in treating BC cells. Folic acid conjugated nanocarriers have shown remarkable efficiency in targeting overexpressed folate receptors on the surface of BC cells. Binding of these target-specific folate-conjugated nanocarriers substantially improves the internalization of chemotherapeutics in BC cells, without much exposing the other parts of the body. Simultaneously, these folate-- conjugated nanocarriers provide imaging for regular monitoring of targeted drug delivery systems and their responses to an anticancer therapy. Therefore, this review demonstrates the potential of folate-conjugated nanotherapeutics for the treatment and theranostic approaches against BC along with the significant challenges to anticancer therapy, and the prospective insights into the clinical importance and effectiveness of folate conjugate nanocarriers.

Cell Signaling pathways form an integral part of our existence that allows the cells to comprehend a stimulus and respond back. Such reactions to external cues from the environment are required and are essential to regulate the normal functioning of our body. Abnormalities in the system arise when there are errors developed in these signals, resulting in a complication or a disease. Presently, respiratory diseases contribute to being the third leading cause of morbidity worldwide. According to the current statistics, over 339 million people are asthmatic, 65 million are suffering from COPD, 2.3 million are lung cancer patients and 10 million are tuberculosis patients. This toll of statistics with chronic respiratory diseases leaves a heavy burden on society and the nation's annual health expenditure. Hence, a better understanding of the processes governing these cellular pathways will enable us to treat and manage these deadly respiratory diseases effectively. Moreover, it is important to comprehend the synergy and interplay of the cellular signaling pathways in respiratory diseases, which will enable us to explore and develop suitable strategies for targeted drug delivery. This review, in particular, focuses on the major respiratory diseases and further provides an in-depth discussion on the various cell signaling pathways that are involved in the pathophysiology of respiratory diseases. Moreover, the review also analyses the defining concepts about advanced nano-drug delivery systems involving various nanocarriers and propose newer prospects to minimize the current challenges faced by researchers and formulation scientists.

Prostate cancer (PCa) is the leading cause of death by cancer in men. Because of the drastic decline in the survival rate of PCa patients with advanced/metastatic disease, early diagnosis of disease and therapy without toxic side effects is crucial. Chemotherapy is widely used to control the progression of PCa at the later stages; however, it is associated with off-target toxicities and severe adverse effects due to the lack of specificity. Delivery of therapeutic or diagnostic agents by using targeted nanoparticles is a promising strategy to enhance accuracy and sensitivity of diagnosis of PCa and to increase efficacy and specificity of therapeutic agents. Numerous efforts have been made in past decades to create nanoparticles with different architectural bases for specific delivery payloads to prostate tumors. Major PCa associated cell membrane protein markers identified as targets for such purposes include folate receptor, sigma receptors, transferrin receptor, gastrin-releasing peptide receptor, urokinase plasminogen activator receptor, and prostate specific membrane antigen. Among these markers, prostate specific membrane antigen has emerged as an extremely specific and sensitive targetable marker for designing targeted nanoparticle-based delivery systems for PCa. In this article, we review contemporary advances in design, specificity, and efficacy of nanoparticles functionalized against PCa. Whenever feasible, both diagnostic as well as therapeutic applications are discussed.

Sericin is a unique proteinaceous biopolymer obtained from cocoons of Bombyx Mori. It has become very popular since it is bestowed with numerous health benefits. Sericin is composed of 18 types of amino acids, out of which 8 amino acids play a significant role in human metabolic pathways. Sericin is easily amenable to make into novel dosage forms and also has been conferred with numerous therapeutic activities such as wound healing, antihypertensive, neuro-protective, antitumor, anti-diabetic, anti-wrinkle, anti-ageing and antioxidant amongst various others. This review summarizes the current status of sericin, as a therapeutic moiety with a focus on active constituents as well as their proposed mechanism in the treatment of various chronic diseases. It also summarizes previous and current in-vitro, in-vivo, cell lines studies and clinical trials based pieces of evidence corroborating the therapeutic activities of sericin.

Cancer accounts for the second major cause of death globally. Conventional cancer therapies lead to systemic toxicity that forbids their long term application. Besides, tumor resistance and recurrence have been observed in the majority of cases. Thus, the development of such therapy, which will pose minimum side effects, is the need of the hour. Curcumin or diferuloylmethane (CUR) is a natural polyphenol bioactive (obtained from Curcuma longa) which possesses anti-cancer and chemo-preventive activity. It acts by modulating various components of signaling cascades that are involved in cancer cell proliferation, invasion, and apoptosis process. It interacts with the adaptive and innate immune systems of our body and causes tumor regression. This may be the reason behind the attainment of in vivo anti-tumor activity at a very low concentration. Its ease of availability, safety profile, low cost, and multifaceted role in cancer prevention and treatment has made it a promising agent for chemoprevention of many cancers. Regardless of the phenomenal properties, its clinical utility is haltered due to its low aqueous solubility, poor bioavailability, rapid metabolism, and low cellular uptake. In the last few years, a variety of novel drug carriers have been fabricated to enhance the bioavailability and pharmacokinetic profile of CUR to attain better targeting of cancer. In this review, the recent developments in the arena of nanoformulations, like liposomes, polymeric NPs, solid lipid NPs (SNPs), polymeric micelles, nanoemulsions, microspheres, nanogels, etc. in anticancer therapy have been discussed along with a brief overview of the molecular targets for CUR in cancer therapy and role of CUR in cancer immunotherapy.

Steering drug-loaded, site-specific, coated lipid vesicles to the target receptor sites have the potential of plummeting adverse effects and improving the pharmacological response in diverse pathologies of the large bowel, especially the colon. Colonic delivery via oral route has its own challenges, often governed by several glitches such as drug degradation or absorption in the upper GIT, instability of proteins/peptides due to high molecular weight, and peptidase activity in the stomach. Consequently, colon-specific coated liposomal systems (CSLS) offer a potential alternate for not only site-specificity, but protection from proteolytic activity, and prolonged residence time for greater systemic bioavailability. On the other hand, liposomal delivery via the oral route is also cumbersome owing to several barriers such as instability in GIT, difficulty in crossing membranes, and issues related to production at the pilot scale. New advancements in the field of CSLS have successfully improved the stability and permeability of liposomes for oral delivery via modulating the compositions of lipid bilayers, adding polymers or ligands. Despite this ostensible propitiousness, no commercial oral CSLS has advanced from bench to bedside for targeted delivery to the colon as yet. Nevertheless, CSLS has quite fascinated the manufacturers owing to its potential industrial viability, simplistic and low-cost design. Hence, this review aims to decipher the convolutions involved in the engineering process of industrially viable CSLS for colonic delivery.

Despite a great deal of efforts made by researchers and the advances in the technology, the treatment of cancer is very challenging. Significant advances in the field of cancer therapeutics have been made but due to the complexity of solid tumor microenvironment, specially their dense extracellular matrix (which makes the conditions favorable for cancer growth, metastasis and acts as a barrier to the chemotherapeutic drugs as well as nanomedicine), the treatment of solid tumors is difficult. Overexpression of extracellular matrix components such as collagen, hyaluronan and proteoglycans in solid tumor leads to high interstitial fluid pressure, hypoxia, vascular collapse and poor perfusion which hinder the diffusion and convection of the drugs into the tumor tissue. This leads to the emergence of drug resistance and poor antitumor efficacy of chemotherapeutics. A number of approaches are being investigated in order to modulate this barrier for improved outcome of cancer chemotherapy. In this review, recent advances in the various approaches for the modulation of the extracellular matrix barrier of the solid tumor are covered and significant findings are discussed in an attempt to facilitate more investigations in this potential area to normalize the tumor extracellular matrix for improving drug exposure to solid tumor.

Flavonoids are secondary metabolites that are widely distributed in plants. These phenolic compounds are classified into various subgroups based on their structures: flavones, flavonols, isoflavones, flavanones, and anthocyanins. They are known to perform various pharmacological actions like antioxidant, anti-inflammatory, anticancer, antimicrobial, antidiabetic and antiallergic, etc. Diabetes is a chronic progressive metabolic disorder that affects several biochemical pathways and leads to secondary complications such as neuropathy, retinopathy, nephropathy, and cardiomyopathy. Among them, the management of diabetic neuropathy is one of the major challenges for physicians as well as the pharmaceutical industries. Naturally occurring flavonoids are extensively used for the treatment of diabetes and its related complications due to their antioxidant properties. Moreover, flavonoids inhibit various pathways that are involved in the progression of diabetic neuropathy like the reduction of oxidative stress, decrease in glycogenolysis, increase glucose utilization, decrease in the formation of advanced glycation end products, and inhibition of the α-glucosidase enzyme. This review entails current updates on the therapeutic perspectives of flavonoids in the treatment of neuropathic pain. This manuscript explains the pathological aspects of neuropathic pain, the chemistry of flavonoids, and their application in amelioration of neuropathic pain through preclinical studies either alone or in combination with other therapeutic agents.

Autoimmune diseases are collectively addressed as chronic conditions initiated by the loss of one’s immunological tolerance, where the body treats its own cells as foreigners or self-antigens. These hay-wired antibodies or immunologically capable cells lead to a variety of disorders like rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, multiple sclerosis and recently included neurodegenerative diseases like Alzheimer’s, Parkinsonism and testicular cancer triggered T-cells induced autoimmune response in testes and brain. Conventional treatments for autoimmune diseases possess several downsides due to unfavourable pharmacokinetic behaviour of drug, reflected by low bioavailability, rapid clearance, offsite toxicity, restricted targeting ability and poor therapeutic outcomes. Novel nanovesicular drug delivery systems including liposomes, niosomes, proniosomes, ethosomes, transferosomes, pharmacosomes, ufasomes and biologically originated exosomes have proved to possess alluring prospects in supporting the combat against autoimmune diseases. These nanovesicles have revitalized available treatment modalities as they are biocompatible, biodegradable, less immunogenic and capable of carrying high drug payloads to deliver both hydrophilic as well as lipophilic drugs to specific sites via passive or active targeting. Due to their unique surface chemistry, they can be decorated with physiological or synthetic ligands to target specific receptors overexpressed in different autoimmune diseases and can even cross the blood-brain barrier. This review presents exhaustive yet concise information on the potential of various nanovesicular systems as drug carriers in improving the overall therapeutic efficiency of the dosage regimen for various autoimmune diseases. The role of endogenous exosomes as biomarkers in the diagnosis and prognosis of autoimmune diseases along with monitoring progress of treatment will also be highlighted.

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.

Topical ocular delivery is an acceptable and familiar approach for the treatment of common ocular diseases. Novel strategies for the treatment of inherited eye diseases include new pharmacologic agents, gene therapy and genome editing, which lead to the expansion of new management options for eye disorders. The topical ocular delivery of nanocarriers is a technique, which has the potential to facilitate novel treatments. Nanocarrier- based strategies have proven effective for site-targeted delivery. This review summarizes recent development in the area of topical delivery of different nanocarriers (Polymer, Vesicular and dispersed systems) for the management of glaucoma, a group of ocular disorders characterized by progressive and accelerated degeneration of the axons of retinal ganglion cells, which make up the optic nerve. Unique cellular targets for glaucoma treatment, primarily the trabecular meshwork of the anterior segment of the eye, make glaucoma facilitated by the use of nanocarriers an ideal disorder for novel molecular therapies.

Ischemic stroke, a leading cause of mortality, results in severe neurological outcomes in the patients. Effective stroke therapies may significantly decrease the extent of injury. For this purpose, novel and efficient drug delivery strategies need to be developed. Among a myriad of therapeutic and drug delivery techniques, exosomes have shown promising results in ischemic stroke either by their intrinsic therapeutic characteristics, which can result in angiogenesis and neurogenesis or by acting as competent, biocompatible drug delivery vehicles to transport neurotherapeutic agents into the brain. In this review, we have discussed different methods of exosome isolation and cargo loading techniques, advantages and disadvantages of using exosomes as a drug delivery carrier and the therapeutic applications of exosomes with a focus on ischemic stroke therapy.