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Quantum dots (QDs) are semiconductor nanocrystals possessing unique optoelectrical properties in that they can emit light energy of specific tunable wavelengths when excited by photons. They are gaining attention nowadays owing to their all-around ability to allow high-quality bio-imaging along with targeted drug delivery. The most lethal central nervous system (CNS) disorders are brain cancers or malignant brain tumors. CNS is guarded by the blood-brain barrier which poses a selective blockade toward drug delivery into the brain. QDs have displayed strong potential to deliver therapeutic agents into the brain successfully. Their bio-imaging capability due to photoluminescence and specific targeting ability through the attachment of ligand biomolecules make them preferable clinical tools for coming times. Biocompatible QDs are emerging as nanotheranostic tools to identify/diagnose and selectively kill cancer cells. The current review focuses on QDs and associated nanoformulations as potential futuristic clinical aids in the continuous battle against brain cancer.

Alzheimer’s disease (AD), a well known aging-induced neurodegenerative disease is related to amyloid proteinopathy. This proteinopathy occurs due to abnormalities in protein folding, structure and thereby its function in cells. The root cause of such kind of proteinopathy and its related neurodegeneration is a disorder in metabolism, rather metabolomics of the major as well as minor nutrients. Metabolomics is the most relevant “omics” platform that offers a great potential for the diagnosis and prognosis of neurodegenerative diseases as an individual’s metabolome. In recent years, the research on such kinds of neurodegenerative diseases, especially aging-related disorders is broadened its scope towards metabolic function. Different neurotransmitter metabolisms are also involved with AD and its associated neurodegeneration. The genetic and epigenetic backgrounds are also noteworthy. In this review, the physiological changes of AD in relation to its corresponding biochemical, genetic and epigenetic involvements including its (AD) therapeutic aspects are discussed.

Apigenin has gained interest recently among researchers as a potential chemotherapeutic agent in cancer, including colorectal cancer, due to its established antiproliferative activity in vitro. Despite its impressive anticancer activity in vitro, poor water solubility and nonspecific distribution in vivo make it difficult for its emergence as a drug candidate. To overcome these problems, we formulated an aptamer-conjugated apigenin-loaded nanoparticle (apt-ANP) to target against the overexpressed colorectal cancer cell surface biomarker epithelial cell adhesion molecule (EpCAM). Aptamer conjugation was conducted on the prepared nanoparticle, characterized (by SEM, TEM, and AFM) and evaluated for its antiproliferative activity toward in vitro colon carcinoma cells and in vivo colorectal cancer model. The aptamer-conjugated nanoformulation had an average size about 226 nm, smooth surface, satisfactory drug loading 17.5 ± 1.3%, and sustained drug-release pattern. The pharmacokinetic profile as well as the biodistribution study demonstrated a maximum retention of apt-ANP in the colon as compared to free drug and aptamer-free apigenin-loaded nanoparticle (ANP). Apt-ANP enhanced therapeutic efficacy to colorectal cancer cells, whereas it minimized off-target cytotoxicity to normal cells.

Azelaic acid (AzA) is a USFDA bioactive prescribed against acne vulgaris. It possesses delivery challenges like poor aqueous solubility, low skin-penetrability, and dose-dependent side effects, which could be overcome by its synergistic combination with tea tree oil (TTO) as a microemulsion (ME)-based hydrogel composite. AzA-TTO ME was prepared to employ pseudo-ternary phase diagram construction. The best AzA-TTO ME was of uniform size (polydispersity index 90%), and negative zeta potential (−1.42 ± 0.25% mV) values. ME hydrogel composite with optimum rheological and textural attributes showed better permeation, retention, and skin-compliant characteristics, vis-a-vis marketed formulation (Aziderm™) when evaluated in Wistar rat skin. In vitro antibacterial efficacy in bacterial strains, i.e., Staphylococcus aureus, Propionibacterium acne, and Staphylococcus epidermidis, was evaluated employing agar well plate diffusion and broth dilution assay. ME hydrogel has shown an increase in zone of inhibition by two folds and a decrease in minimum inhibitory concentration (MIC) by eightfold against P. acnes vis-a-vis AzA. Finally, ME hydrogel composite exhibited a better reduction in the papule density (93.75 ± 1.64%) in comparison to Aziderm™ 72.69 ± 4.67%) on acne as developed in rats by inducing testosterone. Thus, the developed AzA-TTO ME hydrogel composite promises an efficacious and comparatively safer drug delivery system for the topical therapy of acne vulgaris. Graphical abstract

Diltiazem, a calcium ion cellular influx inhibitor is known for its limited and variable bioavailability. This study is intended to explore the benefits of microemulsion formulation as an oral drug delivery system for immediate release to improve the bioavailability and efficacy of Diltiazem. Methods: Oil in water microemulsion was prepared using the simple water titration method. The optimized formulation was evaluated for physicochemical parameters like viscosity, pH, conductivity, and accelerated stability studies. In vitro release, diltiazem microemulsion was investigated.

The human eye can be a tricky issue for topical administration of the drugs due to its unique anatomical arrangements of surface tissue and corneal impermeability. Topical instillation of drugs in the form of eye drops is the major and well-accepted route of administration for the treatment of varied eye disorders. Conventional ophthalmic drug delivery systems often lead to poor bioavailability and thus reduced therapeutic response. Several new preparations are developed to enhance the contact time of the medicament on the surface of the eye. Successful results have been obtained in the form of inserts and collagen shields. However, these preparations have also some disadvantages, such as poor patient compliance, particularly in the case of elderly patients. These problems could be solved by using nanoparticles laden in situ gel-forming systems that exhibit phase transition from solution to gel. These nanoparticle in situ gel systems may be formulated as eye drops suitable for administration through instillation into the eye, which upon exposure to the eye, stimulated by various ocular physiological factors, converts to the gel phase. The advantage of those formulations is that unlike inserts and films they do not require complicated equipment for manufacture and that they are scalable without any difficulty. The objective of the present study was to prepare a pH-dependent nanoparticle-laden in situ gel system for Ciprofloxacin, to prolong the release of the drug into the ocular compartment. No incompatibility was found between the drug and the excipients. Nanoparticles were developed using the nanoprecipitation technique. Eudragit RL 100 was used as the polymer. While the in situ gel solution was formulated using chitosan as polymer. The Ciprofloxacin nanoparticles were measured for particle size and the average particle size was ranged from 295.3-458.7 nm. Entrapment efficiency ranged from 13.83% to 6.29%. Nanoparticleladen in situ gels had the pH of the formulati

Metronidazole is a synthetic nitroimidazole derived with antimicrobial and anti-inflammatory properties. The aqueous solubility of this drug is poor which results from low bioavailability. Limited effects on the removal of bacteria are shown in the local administration of plain metronidazole. The microemulsion system proves the efficacy of solubility and dissolution improvement of poorly watersoluble drugs such as metronidazole. The objective of this project work is to prepare and evaluate metronidazole containing topical water-in-oil microemulsion and to compare its effectiveness to other commercially available products. In this formulation, tween 80 is used as a surfactant and PEG 400 is used as a co-surfactant. In the oil phase, isopropyl myristate is used. Distilled water is used as the hydrophilic phase. The formulation of metronidazole containing microemulsion was evaluated for physicochemical parameters like pH, viscosity, conductivity, accelerated stability studies. In vitro release study was also performed to evaluate the release kinetics.

Aging weakens and deregulates the immune system and plays an impact on the central nervous system (CNS). A crosstalk in between the CNS-mediated immune system and the body's overall innate immunity is often found to increase and subsequently accelerate neurodegeneration and behavioural impairment during aging. Dietary calorie restriction (CR) is found to be a beneficial non-invasive anti-aging therapy as it shows rejuvenation of stress response, brain functions and behaviour during aging. The present investigation deals with the consequence of CR diet supplementation for two different duration (one and two consecutive months) on aging-related alteration of the immune response in male albino Wistar rats at the level of (a) lymphocyte viability, proliferation, cytotoxicity, and DNA fragmentation in blood, spleen, and thymus and (b) cytokines (IL-6, IL-10, and TNF-α) in blood, spleen, thymus and different brain-regions to understand the effect of CR diet on neuroimmune system. The results depict that CR diet consumption for consecutive one and two months by the aged (18 and 24 months) rats significantly attenuated the aging-related (a) decrease of blood, splenic and thymic lymphocyte viability, proliferative activity, cytotoxicity, and IL-10 level and (b) increase of (i) blood, splenic and thymic DNA fragmentation and (ii) IL-6 and TNF-α level in those tissues and also in different brain regions. Unlike older rats, in young (4 months) rats, the consumption of CR diet under similar conditions affected those above-mentioned immune parameters reversibly and adversely. This study concludes that (a) aging significantly (p < 0.01) deregulates the above-mentioned immune parameters, (b) consecutive consumption of CR diet for one and two months is (i) beneficial (p < 0.05) to the aging-related immune system [lymphocyte viability, lymphocyte proliferation, cytotoxicity, pro (IL-6 and TNF-α)- and anti (IL-10)-inflammatory cytokines], but (ii) adverse (p < 0.05) to the immune parameters of the young rats, and (c) consumption of CR diet for consecutive two months is more potent (p < 0.05) than that due to one month.

Nowadays, the use of polymers is almost indispensable to the wide range of applications. Despite their unbeatable usefulness in the biomedical field, nonrenewable resourses, environmental pollution, and biocompatibility are the major limitations that restrict the predominant use of synthetic polymers. Thus, an expedition of the utilization of biopolymers is on a rise. Recently, the development of novel drug delivery systems or nanomedicine utilizing biopolymers enables us to prevent, treat, and diagnose early diseases with unparalleled efficiency and to ensure the accuracy even up to the molecular and genetic levels. This chapter focuses on the applications of biopolymers especially in the field of nanomedicine. Herein, we have briefly described the synthesis, characterization of the largely used and potential biopolymers, and their classifications. In addition, a special emphasis has been given on the uses of biopolymers in the drug delivery approaches from the research viewpoint to clinical applications. The chapter also describes the usefulness of aspiring biopolymers in the current nanomedicine development.

Alzheimer's disease (AD), a well known aging-induced neurodegenerative disease is related to amyloid proteinopathy. This proteinopathy occurs due to abnormalities in protein folding, structure and thereby its function in cells. The root cause of such kind of proteinopathy and its related neurodegeneration is a disorder in metabolism, rather metabolomics of the major as well as minor nutrients. Metabolomics is the most relevant "omics" platform that offers a great potential for the diagnosis and prognosis of neurodegenerative diseases as an individual's metabolome. In recent years, the research on such kinds of neurodegenerative diseases, especially aging-related disorders is broadened its scope towards metabolic function. Different neurotransmitter metabolisms are also involved with AD and its associated neurodegeneration. The genetic and epigenetic backgrounds are also noteworthy. In this review, the physiological changes of AD in relation to its corresponding biochemical, genetic and epigenetic involvements including its (AD) therapeutic aspects are discussed.

Systemic fungal infection in pulmonary tissue and viral infections affecting peripheral nerve claim millions of lives every year. The inability of therapeutics to reach the diseased sites at an optimum concentration, lack of patient-friendly delivery strategies, and inability of delivery strategies to penetrate and/or release the therapeutic payload at the diseased sites, keeping the normal cells unaffected, are some of the reasons which demand alternative or other methods to successfully deliver drug to affected sites. Since the end of the last century, a novel drug delivery system (drug-nanocarrier system) has reached a new benchmark with the application of nanomedicine in the treatment of fatal metabolic disorders and infectious diseases. Despite its ability to increase permeability and penetrability to cells/tissues/organs, its uncontrolled biodistribution may cause cytotoxicity to nontargeted cells, resulting in improper therapeutic management. Therefore, ligand-based active targeting strategies are most popularly exploited by researchers around the world to develop site-specific targeting of diseased sites. A plethora of site-specific nanomedicines has been developed on the laboratory scale based on conventional active targeting strategies with ligands. Even after a lot of sincere efforts, the translation of laboratory to clinic is very limited due to toxicity, stability, and the nonspecific nature of ligands. Therefore, certain nonconventional approaches of targeting therapeutics, such as gene-silencing technology, management of glioma by incorporation of brain-mimicking lipid in nanoliposomal formulations, chemical-mediated nanoliposomal formulations specifically targeted to peripheral nervous systems (PNS), and innovation of novel delivery devices, offer significant promise for effective therapeutic management. This chapter focuses on the pros and cons and future prospects of various conventional and nonconventional approaches of drug targeting with an insight to develop powerful therapeutic weapons for effective therapeutic management of deadly diseases.

Aging is known to affect adversely the corticosterone status and the brain function including cognition. Calorie restricted (CR) diet has been found to improve brain aging. The objective of the present investigation is to study the effect of short-term CR diet without any food deprivation on aging-induced impairment of cognitive function in relation to the corticosterone status and the brain regional GABA system. The result showed that aging-induced deregulation of the brain regional GABA system, increase in plasma and adrenal corticosterone levels and cognitive impairment were attenuated with short-term CR diet supplementation for consecutive 1 and 2 months to the aged (18 and 24 months) rats. But in young rats (4 months) consumption of the same CR diet under similar conditions reversibly affected those above-mentioned parameters. These results, thus suggest that (a) aging down-regulates brain regional GABA system with an up-regulation of corticosterone status and impairment of cognitive function, (b) CR diet consumption improves this aging-induced deregulation of brain regional GABA system, corticosterone status, and cognitive function, (c) these attenuating effects of CR diet are greater with a longer period of consumption but (d) CR diet consumption is harmful to young rats as observed in those parameters.