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Vaginal candidiasis is a common form of infection in women caused by Candida species. Due to several drawbacks of conventional treatments, the current research is attempted to formulate and optimize a miconazole nitrate-loaded in situ spray gel for vaginal candidiasis. The stimuli-responsive (pH and thermo-responsive) polymers selected for the in situ gel were chitosan and poloxamer 407, respectively, whereas hydroxypropyl methylcellulose (HPMC) was introduced in the formulation to further improve the mucoadhesive property. The dispersion of each polymer was carried out using the cold method, whereas the optimization of the formulation was achieved using Box-Behnken statistical design considering viscosity and gelation temperature as dependent variables. Present design achieved the optimized outcome with HPMC, poloxamer and chitosan at 0.52% (w/v), 18.68% (w/v) and 0.41% (w/v), respectively. Evaluation of drug-excipients compatibility was performed using differential scanning calorimetry, Fourier transform infrared spectroscopy, and thermogravimetric analysis where the results showed the absence of any chemical interaction between the polymers and drug component. The optimized formulation showed gelation temperature at 31°C allowing in situ phase transition in a vaginal environment; pH of 4.21 is suitable for use in the vaginal cavity, and appropriate viscosity (290 cP) at storage temperature (below 30°C) would allow spraying at ease, whereas strong mucoadhesive force (22.4±0.513 g) would prevent leaking of the formulation after application. The drug release profile showed sustained release up to 24 h with a cumulative drug release of 81.72%, which is significantly better than the marketed miconazole nitrate cream. In addition, an improved antifungal activity could be correlated to the sustained release of the drug from the formulation. Finally, the safety of the formulation was established while tested on HaCaT cell lines. Based on our findings, it could be concluded that the in situ hydrogel formulation using stimuli-responsive polymers could be a viable alternative to the conventional dosage form that can help to reduce the frequency of administration with ease of application to the site of infection, thus will provide better patient compliance.

Abstract: Alzheimer's disease (AD) is a multifactorial, progressive, neurodegenerative disorder, manifested by the loss of memory and cognitive abilities, behavioral disturbance and progressive impairment of activities of daily life. The sharp rise in the number of AD patients has brought it with-in the top eight health issues in the world. It is associated with the distribution of misfolded aggre-gates of protein within the brain. However, Alois Alzheimer initially mentioned that the reduction in brain volume in AD might be associated with the “deposition of a special substance in the cortex”. The resulting plaque found in extracellular space in the AD brain and hippocampus region, known as senile plaques, is the characteristic feature underlying Alzheimer’s pathology, where the role of amy-loid-β (Aβ) peptide formation from proteolytic cleavage of amyloid precursor protein (APP) by secre-tase enzyme is eminent. Therefore, this review has highlighted the molecular pathophysiology of AD with a variety of available diagnostic and treatment strategies for the management of the disease, with a focus on the advancement toward clinical research to provide new effective and safe tool in the diagnosis, treatment or management of AD.

Aim: To formulate and characterize a palm-oil-in-water-based α-Mangostin nano-emulsion (PO-AMNE) endodontic irrigant, in order to evaluate its antibacterial efficacy against Enterococcus faecalis, Staphylococcus epidermidis, and Candida albicans biofilms, as well as its capacity to remove smear layer. Methods: The solubility of α-Mangostin in various oils was determined and selected, surfactants and co-surfactants were used for the nano-emulsion trial. PO-AMNE was prepared and optimized. The MIC was performed, and the antimicrobial efficacy was estimated against biofilms. The optimized 0.2% PO-AMNE irrigant antimicrobial efficacy in a tooth model was done using colony-forming units. The treated teeth were processed by scanning electron microscopic examination for debris and smear layer removal. An Alamar Blue assay was used to evaluate cell viability. The optimization of the PO-AMNE irrigant was performed using Box–Behnken statistical design. Results: The optimized 0.2% PO-AMNE irrigant was found to have a particle size of 340.9 nm with 0.246 PDI of the dispersed droplets, and a zeta potential (mV) of −27.2 ± 0.7 mV. The MIC values showed that 0.2% PO-AMNE (1.22 ± 0.02) were comparable to 2% CHX (1.33 ± 0.01), and 3.25% NaOCl (2.2 ± 0.09) had the least inhibition for E. faecalis. NaOCl (3.25%) showed the maximum inhibition of S. epidermidis (0.26 ± 0.05), whereas 0.2% PO-AMNE (1.25 ± 0.0) was comparable to 2% CHX (1.86 ± 0.07). For C. albicans, 2% CHX (8.12 ± 0.12) showed the least inhibition as compared to 0.2% PO-AMNE (1.23 ± 0.02) and 3.25% NaOCl (0.59 ± 0.02). The 0.2% PO-AMNE irrigant was then evaluated for its antimicrobial efficacy against the three biofilms, using colony-forming units. The 0.2% PO-AMNE was comparable to both 3.25% NaOCl and 2% CHX in inhibiting the growth of biofilms. The 0.2% PO-AMNE and 17% EDTA eliminated the smear layer with the lowest mean scores (p < 0.001). Finally, 0.2% PO-AMNE was shown to be biocompatible when compared to 17% EDTA, 3.25% NaOCl, and 2% CHX in immortalized oral keratinocyte cells. Conclusion: Overall, the formulated 0.2% PO-AMNE irrigant was an effective antimicrobial and biocompatible which could combat endodontic-infection-related polymicrobial biofilms.

The advancement of delivery tools for therapeutic agents has brought several novel formulations with increased drug loading, sustained release, targeted delivery, and prolonged efficacy. Amongst the several novel delivery approaches, multivesicular liposome has gained potential interest because this delivery system possesses the above advantages. In addition, this multivesicular liposomal delivery prevents degradation of the entrapped drug within the physiological environment while administered. The special structure of the vesicles allowed successful entrapment of hydrophobic and hydrophilic therapeutic agents, including proteins and peptides. Furthermore, this novel formulation could maintain the desired drug concentration in the plasma for a prolonged period, which helps to reduce the dosing frequencies, improve bioavailability, and safety. This tool could also provide stability of the formulation, and finally gaining patient compliance. Several multivesicular liposomes received approval for clinical research, while others are at different stages of laboratory research. In this review, we have focused on the preparation of multivesicular liposomes along with their application in different ailments for the improvement of the performance of the entrapped drug. Moreover, the challenges of delivering multivesicular vesicles have also been emphasized. Overall, it could be inferred that multivesicular liposomal delivery is a platform of advanced drug delivery with improved efficacy and safety.

Curcumin, a natural polyphenol from Curcuma longa, is known to possess diversified pharmacological roles including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic properties; however, its bioavailability is severely limited due to its poor solubility, poor absorption, rapid metabolism, and significant elimination. Hydrazinocurcumin (HZC), a novel analogue of curcumin has been reported to overcome the limitations of curcumin and also possesses multiple pharmacological activities. The present study aimed to evaluate the unexplored pharmacokinetic profile of this agent in experimental rats. Drug formulations were administered to the experimental animals via oral, intravenous and intraperitoneal routes. Blood samples were collected at different pre-determined time intervals to determine the pharmacokinetic parameters. To understand the biodistribution profile of HCZ, tissue samples were isolated from different groups of Sprague–Dawley rats at different time points. The pharmacokinetic parameters of HZC were evaluated after administration through oral (100 mg/kg), intraperitoneal (100 mg/kg) and intravenous (10 mg/kg) routes. Significantly (p

Background Breast cancer (BC) is one of the most common and prevalent cancer types among women. It is caused mainly due to mutations in receptors of estrogen or progesterone. There are several conventional treatment strategies available which include chemotherapy, radiation therapy, and partial or entire mastectomy. These are being most frequently used by most of the healthcare professionals for the treatment of BC. These commonly traditional forms of available treatment therapy, however, were often associated with multiple adverse effects, thus reducing patient compliance. Objective This review focuses on therapeutic strategies driven by nanotechnology that are recognized as a frontline therapy to enhance therapeutic effectiveness and the unintended side-effects associated with incorporated anticancer drugs in the treatment of breast cancer. Results Although there are several nanocarriers available, the folic acid conjugated nanocarriers have shown remarkable efficiency of specific targeting due to their promising specificity for overexpressed folate receptors on the surface of breast cancer cells. The target-specificity of folate-conjugated nanocarriers results in a substantial improvement in medication internalization in breast cancer cells and further decreases accumulation into the non-target organs. Despite having an excellent therapeutic anticancer efficacy, folate-conjugated nanocarriers have also evidenced of having noninvasive imaging for regular monitoring of targeted drug delivery system and their responses to an anticancer therapy. Conclusions In addition, the objective of this review is to demonstrate the potential of folate-conjugated nanotherapeutics for the treatment of breast cancer along with the significant challenges to anticancer therapy, and the prospective insights on its clinical importance and effectiveness of folate conjugate nanocarriers.

The application of medicinal plants has captured the interest of researchers in recent times due to their potent therapeutic properties and a better safety profile. The prominent role of herbal products in treating and preventing multiple diseases dates back to ancient history and most of the modern drugs today originated from their significant sources owing to their ability to control multiple targets via different signalling pathways. Among them, flavonoids consist of a large group of polyphenols, which are well known for their various therapeutic benefits. Rutin is considered one of the attractive phytochemicals and important flavonoids in the pharmaceutical industry due to its diverse pharmacological activities via various underlying molecular mechanisms. It is usually prescribed for various disease conditions such as varicosities, haemorrhoids and internal haemorrhage. In this review, we have discussed and highlighted the different molecular mechanisms attributed to the various pharmacological activities of rutin, such as antioxidant, anti-inflammatory, anticancer, anti-allergic and antidiabetic. This review will be beneficial to herbal, biological and molecular scientists in understanding the pharmacological relevance of rutin at the molecular level.

Theranostics has the potential to revolutionize the diagnosis, treatment, and prognosis of cancer, where novel drug delivery systems could be used to detect the disease at an early stage with instantaneous treatment. Various preclinical approaches of nanoemulsions with entrapped contrast and chemotherapeutic agents have been documented to act specifically on the tumor microenvironment (TME) for both diagnostic and therapeutic purposes. However, bringing these theranostic nanoemulsions through preclinical trials to patients requires several fundamental hurdles to be overcome, including the in vivo behavior of the delivery tool, degradation, and clearance from the system, as well as long-term toxicities. Here, we discuss recent advances in the application of nanoemulsions in molecular imaging with simultaneous therapeutic efficacy in a single delivery system.

The collection of different bulk materials forms the nanoparticles, where the properties of the nanoparticle are solely different from the individual components before being ensembled. Selfassembled nanoparticles are basically a group of complex functional units that are formed by gathering the individual bulk components of the system. It includes micelles, polymeric nanoparticle, carbon nanotubes, liposomes and niosomes, etc. This self-assembly has progressively heightened interest to control the final complex structure of the nanoparticle and its associated properties. The main challenge of formulating self-assembled nanoparticle is to improve the delivery system, bioavailability, enhance circulation time, confer molecular targeting, controlled release, protection of the incorporated drug from external environment and also serve as nanocarriers for macromolecules. Ultimately, these self-assembled nanoparticles facilitate to overcome the physiological barriers in vivo. Self-assembly is an equilibrium process where both individual and assembled components are subsisting in equilibrium. It is a bottom up approach in which molecules are assembled spontaneously, non-covalently into a stable and welldefined structure. There are different approaches that have been adopted in fabrication of self-assembled nanoparticles by the researchers. The current review is enriched with strategies for nanoparticle selfassembly, associated properties, and its application in therapy.

Background: It has been hypothesized that delivery of aripiprazole through nanoemulsion formulation would better deliver the drug into the central nervous system to treat major depressive conditions in psychological patients. Due course of formulation development, to determine solubility of the drug in different matrices and nanoemulsion is an important step. Materials & Methods: Therefore, a simple, rapid and selective reversed phase high performance liquid chromatographic (RP-HPLC) method was developed and validated for the determination of aripiprazole as per International Conference of Harmonization (ICH) guidelines. Satisfactory analysis method was employed for the quantitative determination of aripiprazole during pre-formulation development. Results and Discussion: The separation technique was achieved using the mobile phases of methanol-acetonitrile, 80:20 (v/v) delivered at 1.0 mL.min-1 flow rate through HIQ SIL C18 250x4.6 mm (5 μm particle size) column and detected at 218 nm wavelength. The method depicted linear calibration plots within the range of 5 to 50 µg.mL-1 with a determination coefficient (r2) of 0.9991 calculated by least square regression method. The validated method was sensitive with LOD of 10.0 ng.mL-1 and 30.0 ng.mL-1 of LOQ. The intra-day and inter-day precision values were ranged between 0.37-0.89 and 0.63-1.11 respectively, with accuracy ranging from 98.24 to 100.88 and 97.03 to 100.88, respectively. This developed and validated method was found to be sensitive for the determination of aripiprazole for the first time from various oils, surfactants, co-surfactants, and nanoemulsion formulation. Conclusion: This RP-HPLC method was successfully implemented for the quantitative determination of aripiprazole at developmental stages of nanoemulsion formulation.

Nanoparticles are potential tools for delivering therapeutics to the target site by several mechanisms. These miniaturized carriers are architected in such a way to provide passive targeting capability, which enhances the permeability and retention effect of the carrier within the biological system; simultaneously, active targeting can increase the target-specific delivery of the therapeutics through ligand attachment. Thus, ligand functionalization to the surface of the nanoparticles can be performed using proteins, peptides, polysaccharides, aptamers, and other small molecules. There are different methods for conjugating these ligands to the surface of the nanocarriers. Upon administration, these ligand-adorned nanoparticles circulate in the biological system and concentrate to the specific region for therapeutic efficacy, where the carrier is internalized to exert its biological role. Active targeting-based researches are expanding tremendously for their superior outcomes in different preclinical and clinical studies. Therefore, this chapter focuses on different methods for developing surface-engineered nanoparticles, treatment of different diseases, and diagnosis and theranostic approaches in different medical applications.

Cancer is associated with a comprehensive burden that significantly affects patient's quality of life. Even though patients' disease condition is improving following conventional therapies, researchers are studying alternative tools that can penetrate solid tumours to deliver the therapeutics due to issues of developing resistance by the cancer cells. Treating cancer is not the only the goal in cancer therapy; it also includes protecting non-cancerous cells from the toxic effects of anti-cancer agents. Thus, various advanced techniques, such as cell-based drug delivery, bacteria-mediated therapy, and nanoparticles, are devised for site-specific delivery of drugs. One of the novel methods that can be targeted to deliver anti-cancer agents is by utilising genetically modified non-pathogenic bacterial species. This is due to the ability of bacterial species to multiply selectively or non-selectively on tumour cells, resulting in biofilms that leads to disruption of metastasis process. In preclinical studies, this technology has shown significant results in terms of efficacy, and some are currently under investigation. Therefore, researchers have conducted studies on bacteria transporting the anti-cancer drug to targeted tumours. Alternatively, bacterial ghosts and bacterial spores are utilised to deliver anti-cancer drugs. Although in vivo studies of bacteria-mediated cancer therapy have shown successful outcome, further research on bacteria, specifically their targeting mechanism, is required to establish a complete clinical approach in cancer treatment. This review has focused on the up-to-date understanding of bacteria as a therapeutic carrier in the treatment of cancer as an emerging field.

Skin cancer, one of the most prevalent cancers worldwide, has demonstrated an alarming increase in prevalence and mortality. Hence, it is a public health issue and a high burden of disease, contributing to the economic burden in its treatment. There are multiple treatment options available for skin cancer, ranging from chemotherapy to surgery. However, these conventional treatment modalities possess several limitations, urging the need for the development of an effective and safe treatment for skin cancer that could provide targeted drug delivery and site-specific tumor penetration and minimize unwanted systemic toxicity. Therefore, it is vital to understand the critical biological barriers involved in skin cancer therapeutics for the optimal development of the formulations. Various nanocarriers for targeted delivery of chemotherapeutic drugs have been developed and extensively studied to overcome the limitations faced by topical conventional dosage forms. A site-specific vesicular drug delivery system appears to be an attractive strategy in topical drug delivery for the treatment of skin malignancies. In this review, vesicular drug delivery systems, including liposomes, niosomes, ethosomes, and transfersomes in developing novel drug delivery for skin cancer therapeutics, are discussed. Firstly, the prevalence statistics, current treatments, and limitations of convention dosage form for skin cancer treatment are discussed. Then, the common type of nanocarriers involved in the research for skin cancer treatment are summarized. Lastly, the utilization of vesicular drug delivery systems in delivering chemotherapeutics is reviewed and discussed, along with their beneficial aspects over other nanocarriers, safety concerns, and clinical aspects against skin cancer treatment.

Asenapine, an atypical antipsychotic agent, has been approved for the acute and maintenance treatment of schizophrenia and manic episodes of bipolar disorder. However, the extensive hepatic metabolism limits its oral bioavailability. Therefore, the objective of the current investigation was to develop sublingual film containing asenapine to enhance the therapeutic efficacy. Sublingual films containing asenapine were fabricated using polyethylene oxide and hydroxypropyl methylcellulose by solvent casting method. Design of experiment was used as a statistical tool to optimize the proportion of the film-forming polymers in order to establish the critical quality attributes of the drug formulation. The process was studied in detail by assessing risk of each step as well as parameters and material attributes to reduce the risk to a minimum. A control strategy was defined to ensure manufacture of films according to the target product profile by evaluation of intermediate quality attributes at the end of each process step. Results of optimized formulations showed rapid disintegration, adequate folding endurance, good percentage elongation, tensile strength, and viscosity. Besides, the results from the in vitro dissolution/ex vivo permeation studies showed rapid dissolution (100% in 6 min) and higher asenapine permeation (~ 80% in 90 min) through the sublingual epithelium. In vivo study indicates greater asenapine absorption (31.18 ± 5.01% of administered dose) within 5 min and was comparable with marketed formulation. In summary, the designing plan to develop asenapine formulation was successfully achieved with desired characteristics of the delivery tool for sublingual administration.

Brain tumor represents the most lethal form of cancer with the highest mortality and morbidity rates irrespective of age and sex. Advancements in macromolecule-based therapy (such as nucleic acids and peptides) have shown promising roles in the treatment of brain tumor where the phenomenon of severe toxicities due to the conventional chemotherapeutic agents can be circumvented. Despite its preclinical progress, successful targeting of these macromolecules across the blood-brain barrier without altering their physical and chemical characteristics is of great challenge. With the advent of nanotechnology, nowadays targeted delivery of therapeutics is being explored extensively and these macromolecules, including peptides and nucleic acids, have shown initial success in the treatment, where dendrimer has shown its potential for optimal delivery. Dendrimers are being favored as a mode of drug delivery due to their nano-spherical size and structure, high solubilization potential, multivalent surface, and high loading capacity, where biomolecule resembling characteristics of dendritic 3D structures has shown effective delivery of various therapeutic agents to the brain. Armed with targeting ligands to these dendrimers further expedite the transportation of these multifunctional shuttles specifically to the glioblastoma cells. Thus, a focus has been made in this review on therapeutic applications of dendrimer platforms in brain tumor treatment. The future development of dendrimers as a potential platform for nucleic acid and peptide delivery and its promising clinical application could provide effective and target-specific treatment against brain tumors.

Hidradenitis suppurativa (HS) has been considered an orphan disease with limited treatments available. The available topical treatment for this condition is clindamycin lotion; however, short retention and frequent application are the main setbacks. Thus, the present study aimed to attain an optimized antibacterial in situ spray formulation for the hidradenitis suppurativa skin condition, which gels once in contact with the skin surface at around 37 °C and possesses bioadhesion as well as sustained-release properties of the incorporated drug. Different concentrations of thermo-reversible gelling polymer, Pluronic F-127, were investigated along with the selected bioadhesive polymers, HPMC and SA. The optimized formulation F3 consisting of 18% Pluronic F-127 with 0.2% HPMC and 0.2% SA was characterized based on various physicochemical properties. The gelation temperature of F3 was found to be 29.0 ± 0.50 °C with a gelation time of 1.35 ± 0.40 min and a pH of 5.8. F3 had the viscosity of 178.50 ± 5.50 cP at 25 °C and 7800 ± 200 cP at 37 °C as the gel set. The optimized formulation was found to be bioadhesive and cytocompatible. Cumulative drug release was 65.05% within the time-frame of 8 h; the release pattern of the drug followed zero-order kinetics with the Higuchi release mechanism. The average zone of inhibition was found to be 43.44 ± 1.34 mm. The properties of F3 formulation reflect to improve residence time at the site of application and can enhance sustained drug release. Therefore, it could be concluded that optimized formulation has better retention and enhanced antimicrobial activity for superior efficacy against HS.

Untainted environment promotes health, but the last few decades experienced steep upsurge in environmental contaminants posing detrimental physiological impact. The responsible factors mainly include the exponential growth of human population, havoc rise in industrialization, poorly planned urbanization, and slapdash environment management. Environmental degradation can increase the likelihood of human exposure to heavy metals, resulting in health consequences such as reproductive problems. As a result, research into metal-induced causes of reproductive impairment at the genetic, epigenetic, and biochemical levels must be strengthened further. These metals impact upon the female reproduction at all strata of its regulation and functions, be it development, maturation, or endocrine functions, and are linked to an increase in the causes of infertility in women. Chronic exposures to the heavy metals may lead to breast cancer, endometriosis, endometrial cancer, menstrual disorders, and spontaneous abortions, as well as pre-term deliveries, stillbirths. For example, endometriosis, endometrial cancer, and spontaneous abortions are all caused by the metalloestrogen cadmium (Cd); lead (Pb) levels over a certain threshold can cause spontaneous abortion and have a teratogenic impact; toxic amounts of mercury (Hg) have an influence on the menstrual cycle, which can lead to infertility. Impact of environmental exposure to heavy metals on female fertility is therefore a well-known fact. Thus, the underlying mechanisms must be explained and periodically updated, given the growing evidence on the influence of increasing environmental heavy metal load on female fertility. The purpose of this review is to give a concise overview of how heavy metal affects female reproductive health.

Adenosine is a ubiquitous signaling nucleoside molecule, released from different cells within the body to act on vasculature and immunoescape. The physiological action on the proliferation of tumour cell has been reported by the presence of high concentration of adenosine within the tumour microenvironment, which results in the progression of the tumour, even leading to metastases. The activity of adenosine exclusively depends upon the interaction with four subtypes of heterodimeric G-protein-coupled adenosine receptors (AR), A1, A2A, A2B, and A3-ARs on the cell surface. Research evidence supports that the activation of those receptors via specific agonist or antagonist can modulate the proliferation of tumour cells. The first category of AR, A1 is known to play an antitumour activity via tumour-associated microglial cells to prevent the development of glioblastomas. A2AAR are found in melanoma, lung, and breast cancer cells, where tumour proliferation is stimulated due to inhibition of the immune response via inhibition of natural killer cells cytotoxicity, T cell activity, and tumourspecific CD4+/CD8+ activity. Alternatively, A2BAR helps in the development of tumour upon activation via upregulation of angiogenin factor in the microvascular endothelial cells, inhibition of MAPK and ERK 1/2 phosphorylation activity. Lastly, A3AR is expressed in low levels in normal cells whereas the expression is upregulated in tumour cells, however, agonists to this receptor inhibit tumour proliferation through modulation of Wnt and NF-κB signaling pathways. Several researchers are in search for potential agents to modulate the overexpressed ARs to control cancer. Active components of A2AAR antagonists and A3AR agonists have already entered in Phase-I clinical research to prove their safety in human. This review focused on novel research targets towards the prevention of cancer progression through stimulation of the overexpressed ARs with the hope to protect lives and advance human health.

Background: The incidence of diabetes is increasing steeply; the number of diabetics has doubled over the past three decades. Surprisingly, the knowledge of type 3c diabetes mellitus (T3cDM) is still unclear to the researchers, scientist and medical practitioners, leading towards erroneous diagnosis, which is sometimes misdiagnosed as type 1 diabetes mellitus (T1DM), or more frequently type 2 diabetes mellitus (T2DM). This review is aimed to outline recent information on the etiology, pathophysiology, diagnostic procedures, and therapeutic management of T3cDM patients. Methods: The literature related to T3cDM was thoroughly searched from the public domains and reviewed extensively to construct this article. Further, existing literature related to the other forms of diabetes is reviewed for projecting the differences among the different forms of diabetes. Detailed and updated information related to epidemiological evidence, risk factors, symptoms, diagnosis, pathogenesis and management is structured in this review. Results: T3cDM is often misdiagnosed as T2DM due to the insufficient knowledge differentiating between T2DM and T3cDM. The pathogenesis of T3cDM is explained which is often linked to the history of chronic pancreatitis, pancreatic cancer. Inflammation, and fibrosis in pancreatic tissue lead to damage both endocrine and exocrine functions, thus leading to insulin/glucagon insufficiency and pancreatic enzyme deficiency. Conclusion: Future advancements should be accompanied by the establishment of a quick diagnostic tool through the understanding of potential biomarkers of the disease and newer treatments for better control of the diseased condition.

Multidrug resistance (MDR) is one of the key barriers in chemotherapy, leading to the generation of insensitive cancer cells towards administered therapy. Genetic and epigenetic alterations of the cells are the consequences of MDR, resulted in drug resistivity, which reflects in impaired delivery of cytotoxic agents to the cancer site. Nanotechnology-based nanocarriers have shown immense shreds of evidence in overcoming these problems, where these promising tools handle desired dosage load of hydrophobic chemotherapeutics to facilitate designing of safe, controlled and effective delivery to specifically at tumor microenvironment. Therefore, encapsulating drugs within the nano-architecture have shown to enhance solubility, bioavailability, drug targeting, where co-administered P-gp inhibitors have additionally combat against developed MDR. Moreover, recent advancement in the stimuli-sensitive delivery of nanocarriers facilitates a tumor-targeted release of the chemotherapeutics to reduce the associated toxicities of chemotherapeutic agents in normal cells. The present article is focused on MDR development strategies in the cancer cell and different nanocarrier-based approaches in circumventing this hurdle to establish an effective therapy against deadliest cancer disease.

Controlled release delivery system of chemotherapeutic agents at the site of colon endorses modern drug-entrapped delivery tools, which release the entrappedagents at a controlled rate for anextended period providing patient compliance and additional protection from the degradinggastric environment. Thus, the present study was aimed to develop and optimize a novel polymeric microsphere of 5-fluorouracil (5-FU) using natural gum katira to obtain an optimal therapeutic response at the colon. Due course of experimentation, in-vivo safety profile of the gum katira in an animal model was established. Modified solvent extraction/evaporation technique wasemployed to encapsulate 5-FU in the natural polymeric microsphere and was characterized using in-vitro studies to investigate particle size, morphology, encapsulation efficiency and release of the drug from developed formulation. Formulated and optimized polymeric microsphere of 5-FU using gum katira polymer own optimal physicochemical characteristics with a fine spherical particle with size ranged from 210.37±7.50 to 314.45±7.80 μm.Targeted microsphere exhibited good cytotoxicity and also has high drug entrapment efficiency, and satisfactory release pattern of the drug within a time frame of 12 h. Finally, we foresee that the optimized polymeric gum katiramicrosphere of 5-FU could be a promising micro-carrier for efficient colon drug targeting delivery tool with improved chemotherapeutic efficacy against colon cancer.

Intranasal delivery has shown to circumvent blood-brain-barrier (BBB) and deliver the drugs into the CNS at a higher rate and extent than other conventional routes. The mechanism of drug transport from nose-to-brain is not fully understood yet, but several neuronal pathways are considered to be involved. Intranasal nanoemulsion for brain targeting is investigated extensively. Higher brain distribution of drug after administering intranasal nanoemulsion was established by many researchers. Issues with nasomucosal clearance are solved by formulating modified nanoemulsion; for instance, mucoadhesive nanoemulsion or in situ nanoemulgel. However, no intranasal nanoemulsion for brain targeted drug delivery has been able to cross the way from 'benches to bed-side' of patients. Possibilities of toxicity by repeated administration, irregular nasal absorption during the diseased condition, use of a high amount of surfactants are few of the persisting challenges that need to overcome in coming days. Understanding the ways how current developments has solved some challenges is necessary. At the same time, the future direction of the research on intranasal nanoemulsion should be figured out based on existing challenges. This review is focused on the current developments of intranasal nanoemulsion with special emphasis on the existing challenges that would help to set future research direction.

Theranostic nanotherapeutic strategy has been widely emphasized now a day to develop next-generation nanomedicine. Dendrimer-entrapped gold nanoparticles (DE-Au-NP) have acquired emerging application in therapeutic, imaging as well as in theranostics sciences. DE-Au-NP decorated with a specific ligand for cancer cells could deliver contrast agents at target sites for imaging as well as chemotherapeutics for anticancer activity. Entrapped Au in DE-Au-NP complex could serve as an excellent contrast agent for CT imaging with better signal intensity to identify initial stages of cancer, whereas its photothermal effect can kill cancerous cells effectively. Although, reported nonspecific binding of DE-Au-NP due to free amine groups and associated toxicities of dendrimer complex could be minimized through PEGylation or acetylation of such surface amines. Recent research on gene delivery also revealed DE-Au-NP as an active tool to deliver plasmids to cancer cells to express/suppress particular protein(s) to combat against cancer.

A single ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that causes inflammation of the colonic mucosa at the distal colon and rectum. The mainstay therapy involves anti-inflammatory immunosuppression based on the disease location and severity. The disadvantages of using systemic corticosteroids for UC treatment is the amplified risk of malignancies and infections. Therefore, topical treatments are safer as they have fewer systemic side effects due to less systemic exposure. In this context, pH sensitive and enzymatically triggered hydrogel of pectin (PC) and polyacrylamide (PAM) has been developed to facilitate colon-targeted delivery of budesonide (BUD) for the treatment of UC. The hydrogels were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), swelling ratio, and drug release. FT-IR spectroscopy confirmed the grafting as well loading of BUD in hydrogel. XRD showed the amorphous nature of hydrogel and increment in crystallinity after drug loading. On the other hand, SEM showed that the hydrogels exhibited a highly porous morphology, which is suitable for drug loading and also demonstrated a pH-responsive swelling behaviour, with decreased swelling in acidic media. The in-vitro release of BUD from the hydrogel exhibited a sustained release behaviour with non-ficken diffusion mechanism. The model that fitted best for BUD released was the Higuchi kinetic model. It was concluded that enzyme/pH dual-sensitive hydrogels are an effective colon-targeted delivery system for UC.

Eyesight is one of the most well-deserved blessings, amid all the five senses in the human body. It captures the raw signals from the outside world to create detailed visual images, granting the ability to witness and gain knowledge about the world. Eyes are exposed directly to the external environment; they are susceptible to the vicissitudes of diseases. The World Health Organization has predicted that the number of individuals affected by eye diseases will rise enormously in the next decades. However, the physical barriers of the eyes and the problems associated with conventional ocular formulations are significant challenges in ophthalmic drug development. This has generated the demand for a sustained ocular drug delivery system, which serves to deliver effective drug concentration at a reduced frequency for consistent therapeutic effect and better patient treatment adherence. Recent advancement in pharmaceutical dosage design has demonstrated that a stimuli-responsive in situ gel system exhibits the favorable characteristics for providing sustained ocular drug delivery and enhanced ocular bioavailability. Stimuli-responsive in situ gels undergo a phase transition (solution–gelation) in response to the ocular environmental temperature, pH, and ions. These stimuli transform the formulation into a gel at the cul de sac to overcome the shortcomings of conventional eye drops, such as rapid nasolacrimal drainage and short contact time with the ocular surface This review highlights the recent successful research outcomes of stimuli-responsive in situ gelling systems in treating in vivo models with glaucoma and various ocular infections. Additionally, it also presents the mechanism, recent development, and safety considerations of stimuli-sensitive in situ gel as the potential sustained ocular delivery system for treating common eye disorders.