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Exosomes are multivesicular bodies of which the plasma membrane fuse to release the caring moiety into the surrounding body fluids. They are well knwon for their function in mediating intercellular connectivity by transferring various biomolecules, such as proteins, RNAs, and lipids, from one cell to another. These “naturally equipped” nanovesicles could be therapeutically targeted or engineered as drug delivery systems. The use of exosomes in cancer detection and prognosis has attracted a great deal of interest from academics. In addition to chemical, biological, and genetic engineering approaches, other current exosomal alteration methodologies hold promise for the advancement of therapeutic medicines for cancer. In this review, we highlight the theranostic potential of exosomes for therapeutic delivery in various cancers.

The aim of the present investigation is to develop zaltoprofen-loaded extended-release (ER) pellets formulation by an extrusion-spheronization technique using glyoxalated pre-gelatinized starch (GP...

Drying is an indispensable operation in the preparation of pharmaceutical powders and always remained one of the energetic tasks in the pharmaceutical industry. Improving the stability, solubility,...

The present investigation aims at development of extended release (ER) pellets using κ-carrageenan-montmorillonite (κ-Carr-MMT) polyelectrolyte complex (PEC) hydrogel. The PEC was used as binder an...

Drug delivery to lungs via pulmonary administration offers potential for the development of new drug delivery systems. Here we fabricated the etofylline (ETO) encapsulated mannose-anchored N,N,N-trimethyl chitosan nanoparticles (Mn-TMC NPs). The prominent characteristics like biocompatibility, controlled release, targeted delivery, high penetrability, enhanced physical stability, and scalability mark Mn-TMC NPs as a viable alternative to various nanoplatform technologies for effective drug delivery. Mannosylation of TMC NPs leads to the evolution of new drug delivery vehicle with gratifying characteristics, and potential benefits in efficient drug therapy. It is widely accepted that following pulmonary administration, the introduction of mannose to the surface of drug nanocarriers provide selective macrophage targeting via receptor-mediated endocytosis. The fabricated Mn-TMC NPs exhibited particle size of 223.3 nm, PDI 0.490, and ζ-potential −19.1 mV, drug-loading capacity 76.26 ± 1.2%, and encapsulation efficiency of 91.75 ± 0.88%. Sustained drug release, biodegradation studies, stability, safety, and aerodynamic behavior revealed the effectiveness of prepared nanoformulation for pulmonary administration. In addition, the in vivo pharmacokinetic studies in Wistar rat model revealed a significant improvement in therapeutic efficacy of ETO, illustrating mannosylation a promising approach for efficient therapy of airway diseases following pulmonary administration.

The primary objective of the study was to investigate the mucoadhesion and gelling behaviour of mucilage isolated from the tubers of Eulophia herbacea (Orchidaceae), and to search the possibility o...

Glioblastoma (GBM) is considered the most dominant and malignant tumor of the brain. The details of the physiological characteristics of GBM, and the blood–brain barrier, highlight the cause behind the significant challenge presented by the disease. The drawbacks and limitations of currently approved therapies demand for a new and advanced system to tackle this invincible looking challenge. Hence, there is a stringent need to develop novel therapeutic strategies that will not only improve the clinical outcomes but also decrease the rate of relapse and adverse effects related to conventional therapies. This chapter deals with the understanding of various advanced therapeutic modalities for the treatment or management of GBM. It also elaborates on different promising technologies and the loopholes of current therapies. This chapter emphasizes the importance of a detailed understanding of GBM biology and its correlation with the development of emerging therapies.

A most fascinating approach of targeting the neurotherapeutics to the brain is the direct transport of drugs along the olfactory and/or trigeminal nerve pathways that initiated in the nose at the olfactory neuroepithelium and terminated in the brain. Since the last decade, the surface modification of the nanomedicines appears to be a key strategy to optimize the drug delivery from the nasal cavity to the brain. This review could be a wonderful cluster of investigations for the researchers engaged in developing novel surface-modified nanomedicines, intended for the direct nose-to-brain drug delivery applications. In conclusion, the authors note here that the strategy of modifying the surface of the nanomedicines could improve the stability, safety, and targetability of the prepared nanocarriers. This could be a budding practical approach, if investigated extensively, and can bring new hopes in the pharmaceutical product development particularly for the brain-targeted drug delivery.

Direct nose-to-brain drug delivery has emerged in recent years as an exceptional drug delivery approach for the noninvasive administration of a variety of drugs and vaccines. In order to evaluate the reliability of this route of drug administration, experimental models are needed. In addition, the correct experimental model provides a precise correlation of the findings when the results are to be extrapolated to man. The primary aim of this chapter is to provide the researchers with a comprehensive overview of various experimental models, viz. in vitro, ex vivo, in vivo, genetic, neurotoxic, and computational models for different preclinical studies involved in direct nose-to-brain drug delivery. In the selection of an appropriate model for investigational studies, several factors such as merits, demerits, ease of handling, and cost effectiveness need to be considered. Finally, authors conclude that this chapter would present an excellent piece of efforts for exploring the availability and selection of a specific experimental model that mimics the major pathological and phenotypic features of any neurological disorder.

The delivery of drugs to CNS has been constrained due to the presence of blood-brain barrier (BBB). The intranasal route involving several pathways (viz., olfactory, trigeminal, and rostral migratory stream-based pathway) has emerged as potential route to bypass the BBB and transport drug directly to the brain. In another terms, intranasal route involves two distinct mechanistic transportation pathways, viz., extracellular and intracellular. Extracellular pathway is responsible for the transportation of drug directly to cerebrospinal fluid (CSF) by passing through paracellular space across the nasal epithelium, then through the perineuronal space to the subarachnoid space of the brain. However, intracellular pathways start with olfactory sensory cell-based endocytosis, followed by axonal transportation to their synaptic clefts in the olfactory bulb where the therapeutic moiety is exocytosed. This chapter inculcates various pathways and transport mechanisms involved in the direct transportation of drugs to the brain. The several case studies involving pharmacokinetics of nanoparticle-based delivery systems when administered intranasally have also been explained in this chapter.

The blood-brain barrier (BBB) poses a major hurdle in the effective delivery of neuroactive drug molecules to the brain microenvironment. BBB hampers the neurotherapy of many neuro-ailments due to restrictive access of neurotherapeutics to the brain regions in desired concentrations. Direct transport of neurotherapeutics from the nose to the brain regions along the well-recognized olfactory and trigeminal nerve pathways seems to be an effective strategy to overcome the BBB, thereby enabling the functional recovery of major neurodegenerative disorders (NDs). The existence of a direct entry point from the nose to the brain encourages scientists to explore the opportunities in optimizing therapies of neuroailments. The present chapter comprehensively covers the neuropathogenesis of various NDs, associated therapeutic targets, and diagnosis of NDs. The authors have also illustrated the potential of nanobiosensors for the rapid detection of NDs. This chapter also highlights the nanotherapeutic strategies investigated for effectively delivering the neurotherapeutics to target the neuronal regions via a direct nose-to-brain transport pathway for effective management of NDs.

This chapter deals with a detailed review of recent technological advancements in the development of new devices for drug delivery, specifically for nasal and pulmonary administration. A successful drug delivery device needs formulation administration in such a way that the maximum amount of drug should reach the target site. The prime focus of this chapter is to keep the audience updated with the current commercial availability of the various drug administration devices. To start with, the authors have briefly introduced the anatomy and physiology of the nose and the lungs. In addition, this review also gives a brief update on the regulatory aspects of drug delivery devices. The authors think that, in the near future, we should expect a range of patient-friendly novel drug delivery devices reaching the market that efficiently deliver the medications, necessarily noninvasive, aid in rapid onset of action, patient-friendly for self-administration, and should exhibit minimum side effects.

The complex geometry of nasal cavity restricts the entry of instilled or sprayed nasal formulation to the target region, hampering the drug effectiveness and thus affecting the therapy. In order to restrict the deposition of nasal formulation at nasal olfactory region so as to achieve a therapeutically effective concentration of the drug in the brain, there is a stringent need to develop an efficient nasal drug administration device. Recently, many pharmaceutical industries have emerged with several advanced nasal drug delivery devices that are technologically sound and therapeutically effective in reaching the brain regions. However, the lack of patient cooperation in breath-powered devices, formulation flexibility, and patient-to-patient variability, many devices are in the pipeline at clinical stages and yet to come at marketplace. The present chapter provides a technological overview of few most widely used nasal administration devices designed for nose-to-brain drug delivery. In addition to this, the anatomical and physiological restrictions hampering the drug delivery to nose and the assessment of nasal drug delivery devices are also the key points of this chapter. A brief overview of patents on nasal drug delivery devices for CNS targeting has also been given at the end of the chapter. Considering the potential outcomes, the mankind may expect few advanced nasal drug administration devices in the hands of end users, in the near future.

The use of nanocarriers for pharmaceutical and clinical applications is a well-established archetype since long time. These nanoparticulate carriers are expected to stay in blood for long time, accumulate at target site in desired extent, and facilitate the targeted drug delivery via target-specific drug-ligand complexes or conjugates in poorly reachable regions of the body. Talking more specifically about brain targeting, the highly dense blood-brain barrier (BBB) restricts the entry of variety of small and macromolecules to the brain regions, thereby put a great challenge to treat central nervous system (CNS) disorders. This fact urges the need of BBB-bypass drug delivery approach, so called direct nose-to-brain drug delivery. In order to improve the therapeutic effectiveness, the delivery strategies are focused on using the nanoparticulate carriers to conquer the BBB and directly targeting the diseased cells in the brain. This review entry highlights the various types of targeting strategies developed for direct nose-to-brain delivery using nanoparticles (NPs) as neurotherapeutic carriers. We hope this chapter containing comprehensive study reports would be a unique cluster of evidences for researchers exploring the direct nose-to-brain targeted drug delivery and would certainly benefit the physicians in improving the therapy for CNS disorders.

The nasal route of administration is gaining a lot of interest these days in order to achieve the efficient brain targeting. The superior therapeutic outcomes of nasal delivery are due to surpassing the demerits of the conventional drug delivery viz. first-pass metabolism, enzymatic degradation in gastric environment, poor absorption rate, and reduced bioavailability. This route suffers several drawbacks viz. mucociliary clearance, reduced residence time, and poor permeability through nasal mucosa, which made it difficult task for the formulators to fabricate the efficient nasal delivery system. The intranasal delivery extends various merits over systemic drug delivery because it directly allows the entry of drug in the brain via olfactory route and trigeminal nerve pathways. In addition, the amount of drug in the olfactory bulb enhances the drug bioavailability and cuts down the drug degradation and loss through systemic clearance. Currently, many vesicular carriers (liposomes, niosomes, ethosomes, transferosomes, virosomes, and novasomes) have shown promising outcomes to encounter the drawbacks of nasal route of drug administration. This chapter includes brief discussion on the above-mentioned vesicular carriers along with their difference in structure, composition, physicochemical properties, penetrability, and drug entrapment efficiency. The efforts taken by the researchers to develop vesicular carriers with an aim to obtain nose-to-brain delivery need a lot more thrust. This chapter also includes the clinical translational updates of various formulations and challenges encountered.

Here we fabricated flaxseed oil-based neuronanoemulsions (NNEs) which were further surface-modified with a mucoadhesive polymer, N,N,N‑trimethyl chitosan (TMC) to form mucoadhesive neuronanoemulsions (mNNEs). The NNEs were loaded with high partitioning ropinirole-dextran sulfate (ROPI-DS) nanoplex and fabricated using hot high-pressure homogenization (HPH) technique. NNEs were optimized using Central Composite experimental design. TMC modified mNNE have not been prepared yet for direct nose to brain drug delivery. Here, an objective to provide controlled drug release with prolonged residence on the nasal mucosa for the treatment of Parkinson's disease (PD) is at prime consideration. Enhanced brain targeting through BBB bypass drug delivery, improved therapeutic efficacy through enhanced retention of mNNE formulation over nasal mucosal membrane, reduced dose and frequency of administration, and safety were further expected outcomes of this experiment. The mNNE formulation was subjected to 6 month stability assessment. The mNNE formulation was administered to the Swiss albino mice model via intranasal route and both, the plasma and brain pharmacokinetics were estimated. The in vivo studies performed on mice exhibited high brain targeting efficiency of mNNE formulation through nose to brain delivery via olfactory pathway. The prepared intranasal mNNEs could be on the clinics, if investigated more for behavioral and neurotoxicity studies.

In the present research, we report the synthesis and in vitro antimicrobial activity of a new series of novel quinazolino-thiadiazoles as fused pharmacophore (3–20). In general, the results of the in vitro antibacterial activity are encouraging, as out of 18 compounds tested, Compounds 3 and 8 with a 4-chlorophenyl and 4-nitro phenyl at C-2 of thiadiazole and chloromethyl substituent at C-2 of quinazolinone displayed a broad spectrum antimicrobial activity against all the strains, while compounds 13 and 16 again with a 4-chlorophenyl and 4-nitrophenyl at C-2 of thiadiazole and ethyl substituent at C-2 of quinazolinone showed the same potency but with a narrower spectrum (Bacterial and Fungal strains) with MIC values of 62.5 µg/ml. The structures of the compounds were confirmed by IR, 1H NMR, 13C NMR and Mass analysis. It is worth to mention that the combination of two biologically active moieties quinazoline and thiadiazole profoundly influences the biological activity.

N,N,N-trimethyl chitosan (TMC), a quaternized hydrophilic derivative of chitosan (CHT), outperformed the well-known solubility issues raised by CHT. The excellent properties offered by TMC provide it a significant edge for nanoparticle (NP) formation over other nanocarrier materials. Recently, TMC NPs have been applied to various fields like pharmaceutical, biomedical, biomaterials, and biotechnological field. The aim of this review is, therefore, to bring the TMC into the limelight so as to appraise it as an attractive functional polymer for nanomedicine applications which is facing oversight, at present, by regulatory agencies and manufacturers. The versatility of surface-tailoring, the capability of further chemical modifications, and the feasibility of ligand-conjugations in TMC polymer will further assist the scientists for reaching new dimensions in the nano-assembly of novel structures based on TMC.

Here we report the development of tristearin-based nanostructured-lipid carriers (NLCs) which were further surface-modified with mucoadhesive N,N,N-trimethyl chitosan (TMC) to form mucoadhesive nanostructured-lipid carriers (mNLCs). The NLCs were loaded with high partitioning ropinirole-dextran sulphate (ROPI-DS) nanoplex. NLCs were optimised using Box-Behnken experimental design. Obtaining controlled drug release with prolonged residence on the nasal mucosa for treating Parkinson’s disease (PD) is a major objective of the present investigation. Enhanced brain targetability and improved therapeutic efficacy are the additional objective of this study. Lyophilised NLCs and mNLCs were characterised in solid state by FTIR, DSC, XRD, and HR-TEM analysis. The bioadhesive strength of mNLCs was observed to be 13.3-folds greater compared to NLCs. Plasma and brain pharmacokinetic studies in mice model demonstrated the potential of mNLCs in nose-to-brain drug delivery via olfactory pathway. If investigated for behavioural and neurotoxicity studies clinically, a commercial formulation for patient looks feasible.

The blood–brain barrier (BBB) is the major obstacle in the effective delivery of neurotherapeutics to the brain microenvironments. The dense membrane hampers the access of many of the therapeutic drugs to reach to the brain regions in sufficient concentrations, leading to poor patient compliance and discontinuation of the neurotherapy. A direct transport of neurotherapeutics from nose to brain regions along the well-known olfactory and trigeminal nerve pathways seems to be an effective strategy to overcome the BBB, and we propose the direct nose-to-brain drug delivery as an effective strategy for safe and noninvasive administration of the neurotherapeutics. Existence of direct entry point from nose to brain encourages the scientists to explore the opportunities in optimizing therapy of neuroailments. This chapter highlights the diagnosis and therapy of major neurodegenerative disorders (NDs) and developments in the nanotechnological areas for effectively delivering the neurotherapeutics to target the neuronal regions via direct nose-to-brain transport.

The graph of drug resistance in cancer is reportedly increasing in terms of therapeutic efficiency. As per the WHO reports, around 70% of death reported in low- and middle-income countries. The increase in death toll was imparted from improper diagnosis and inadequate therapy. The 25% increase in disease burden may be laden due to resistance mutations in cancer during treatment. Exposure of high concentrations of chemotherapeutic agents leads to toxicity in the normal cells. Long-term conventional chemotherapy develops acquired resistance. The conventional therapeutics was not able to target the cancer cell specifically and need to promulgate the use of nanocarrier or bioengineering for the polychemotherapy. Phytochemicals are natural constituents providing alternative therapeutic approach to minimize the resistance. The present review highlights the nano-therapeutic approaches pondering over the conventional chemotherapy. The phytochemicals are extracted, isolated, and purified from daily dietary fibers or natural plants. Natural extractives act via multiple pathways and provide optimum effectiveness against resistance cancer. The poor solubility and bioavailability are major constraints in combination therapy. The nanotechnological approach improves the functional properties transportation across cell barriers, and improves bioavailability. The present review highlights the phytochemical based nanoformulations in improving the therapeutic response and several alternative ways to target resistance cancer. The major implications of phytochemical and chemotherapeutic combination therapy could lead in the future.

This study investigates the extrusion-spheronization performance of some mixtures of co-processed κ-carrageenan and pectin (as excipient), and sodium starch glycolate (as superdisintegrant). Attention is focused with an objective to improve the mechanical stability and the dissolution rate of poorly soluble domperidone (as a model drug). Initially, co-processed κ-carrageenan-pectin excipient is prepared with different ratios of κ-carrageenan and pectin. Different marketed brands of κ-carrageenan (Gelcarin, Aquagel and Eugel) were employed and dried by solvent evaporation method. Further characterization was carried out by SEM, XRD and FTIR analysis. Pellets were prepared using extrusion-spheronization technique. Pellets were evaluated for flow properties, particle size, sphericity, tensile strength, friability, disintegration time and in-vitro drug release studies. Solid-state characterization of pellets was also done by FTIR, DSC and SEM analysis. The mechanical stability and dissolution rate of ...

Present investigation deals with design, development and evaluation of chitosan-based spray-dried nasal mucoadhesive microspheres loaded with diltiazem hydrochloride (DTZ HCl). The principal objectives were to improve therapeutic efficacy through increased residence of microspheres on the nasal mucosa, and avoidance of hepatic first-pass metabolism. Formulation samples were characterized for preliminary physico–chemical parameters, mucoadhesiveness, drug release and release kinetics, mucosal toxicity, stability, and in vivo studies. Central composite experimental design was utilized herein to evaluate the influence of process and formulation variables product performance. Numerical and graphical optimization techniques were used for selecting optimum sample of prepared microspheres, further confirmed by three dimensional response surface plots and multilinear regression model. Results of ANOVA validated the significance of suggested models. Our findings suggest that DTZ-loaded spray-dried chitosan microspheres formulation could be used as a promising approach for intranasal administration which, in sum, improves therapeutic efficacy of the formulation.

The polyelectrolyte complexes (PECs) are versatile formulations formed by electrostatic interactions between oppositely charged biopolymers. PECs have been investigated widely by the researchers to explore the virtues of this formulation viz. high biocompatibility, excellent biodegradability, low toxicity, cost-effective, environment-friendly, and energy-efficient production. The prime object of the present review is to present the prominent features of PECs including mechanism of PEC formation, structural models of PECs, interactions involved in PEC formation, steps involved in PEC fabrication, factors affecting the formation of PECs and applications of PECs. The patents pertaining to PECs have briefly been tabulated as well.

A series of novel quinazoline derivatives were synthesized, virtually screened through different filters and evaluated for their anticonvulsant activity against electrically and chemically induced seizures, compared with that of the standard drugs methaqualone and sodium valproate. Compound 48, 3-(2-aminophenyl)-7-chloro-2-phenylquinazolin-4(3H)-one, was found to be the most potent compound of the series accompanied by relatively low neurotoxicity and low toxicity in the median lethal dose test as compared with the reference drugs. The obtained results showed that compounds 12, 48, 49 and 50 could be useful templates for future design, optimization, and investigation to construct more active analogs.

The near future of drug delivery system would lie in the search for a versatile and innocuous biomaterial, based mostly on natural resources. The tamarind seed xyloglucan (XG) is a natural neutral hemicellulose (hydrophilic polysaccharide) consisting of a main chain of glucan backbone with xylose and galactose side chains. XG is gifted with distinct mucoadhesive and in situ gelling properties which rated XG as an attractive, and functional polymer for numerous drug delivery applications. On these grounds, the present chapter is designed to underline the plausible potential of XG or XG-based systems in drug delivery. The feasibility of surface tailoring, the flexibility of chemical modification, and the possibility as ligand conjugations grant XG an extraordinary attention in the scientific community. The authors are assured that the versatility of XG would meet the expectations of regulatory authorities and the XG-based products will serve the therapeutic needs of the community in the coming years, if sufficiently investigated and promising outcomes are obtained in human subjects.

The brain-blood ratio is an important model correlating the brain-targeting ability of neurotherapeutics with the CNS pharmacokinetics, which need to be presented before the scientific community for exploration of its scientific worth. The purpose of this article is to bring this key concept and its precise discussion to the attention of the researchers.Three major points are discussed herein: First, the significance of brain-blood ratio with respect to investigational neurotherapeutics, and carrier systems and correlation of its research findings with the brain targeting efficiency. Second, the various factors influencing the brain-blood ratio. Third, the various strategies for enhancing the brain-blood ratio. In addition, the benchmark criteria for CNS-likeness of drug molecules and the correlation of brain-blood ratio with brain targeting ability of neurotherapeutics have been tabulated.The brain-blood ratio (also referred to as the brain-plasma ratio) represents one of the tools available today for estimation of CNS pharmacokinetics. It is preferred over other complicated techniques (in situ brain perfusion and microdialysis) due to its ease of use and practicality. We are optimistic that the brain-blood ratio offers an excellent way of evaluating brain-targeting efficiency of neurotherapeutics effectively. In our opinion, it is a very fundamental aspect of brain bioavailability and needs to be presented in a precise way.

The near future of drug delivery system would lie in the search of a versatile and innocuous material, based mostly on the natural resources. The tamarind seed xyloglucan (XG) is a natural neutral hemicellulose and a hydrophilic polysaccharide consisting of a main chain of glucan backbone with xylose and galactose side chains. XG is endowed with idiosyncratic mucoadhesive and in situ gelling properties which rated XG as an attractive, functional polymer for numerous drug delivery applications. In milieu of this, the present review is designed to underline the plausible potential of XG or XG-based systems in drug delivery. The feasibility of surface-tailoring, the flexibility of chemical-modification, and the possibility as ligand-conjugations grant XG an extraordinary consideration in the scientific territory. The authors are hopeful that the versatility of XG would meet the expectations of regulatory authorities and the XG-based products will serve the therapeutic needs of the community in the future, if sufficiently investigated and promising outcomes are obtained in human subjects.

Topical therapy is at the forefront in treating nail ailments (especially onychomycosis and nail psoriasis) due to its local effects, which circumvents systemic adverse events, improves patient compliance and reduces treatment cost. However, the success of topical therapy has been hindered due to poor penetration of topical therapeutics across densely keratinized nail plate barrier. For effective topical therapy across nail plate, ungual drug permeation must be enhanced. Present review is designed to provide an insight into prime aspects of transungual drug delivery viz. nail structure and physiology, various onychopathies, techniques of nail permeation enhancement and in vitro models for trans-nail drug permeation studies. Updated list of drug molecules studied across the nail plate and key commercial products have been furnished with sufficient depth. Patents pertinent to, and current clinical status of transungual drug delivery have also been comprehensively reviewed. This is the first systematic critique encompassing the detailed aspects of transungual drug delivery. In our opinion, transungual drug delivery is a promising avenue for researchers to develop novel formulations, augmenting pharmaceutical industries to commercialize the products for nail disorders.