Advanced Pharmaceutical and Herbal Nanoscience for Targeted Drug Delivery Systems Part I

This introductory chapter reviews the history of nanotechnology and its benefits and challenges in the pharmaceutical field. In general, the chapter summarizes the types of nanoparticles and the techniques used to formulate nanoparticles. In detail, it discusses the principle of nanotechnology in improving solubility and dissolution rate. It discusses and describes different types of nanoparticles, including polymeric, metallic nanoparticles, and other types, such as solid lipid nanoparticles (SLN) and liposomes. Nanosization can be performed by various techniques, including top-down, bottom-up, and combination techniques. The method of these techniques has been discussed in this chapter. One of the disadvantages of nanoparticles is their stability. Nanoparticles suffer from various types of instability problems, including aggregation, sedimentation, and crystal growth. Therefore, in this chapter, the authors discuss the problem of stabilization of nanoparticles and describe the different pathways of physical instability and the mechanism of stabilizers to stabilize the colloidal system. Finally, the importance of herbs and natural products in the medical field and how the use of nanotechnology addresses various drawbacks of herbal products are also discussed.

The development of bioactive components as delivery systems with the use of advanced nanoscience is opening new therapeutic avenues for the management of various diseases. Among recent novel applications, plant phytopharmaceuticals and nutraceuticals are the fastest growing areas of nanotechnology-based research for effective public healthcare. Bioactive compounds, either encapsulated or in entrapped form within novel drug delivery systems, are reported as a booster treatment for various chronic infections and life-threatening diseases, including cancer, cardiovascular disorders, hypertension, diabetes, asthma, malaria, microbial infections, immune disorders, and gastrointestinal disorders. Recently, considerable progress has surged in understanding the factors associated with these diseases. A variety of nanoscience-based formulations such as polymeric matrix nanoparticles, aerosol inhalers/nebulizers nanoemulsions, and vesicular carrier systems, including liposome, phytosome, transfersome, herbosome, ethosome, niosome, have proven valuable in the delivery of bioactive materials. Moreover, it is reported that herbs and herbal bioactive compounds exhibit notable efficacy compared to phytopharmaceuticals and plant extracts fortified within the conventional method of delivery, with enhanced solubility, bioavailability, stability, tissue distribution, abridged toxicity, improved pharmacological efficacy, and protection from physicochemical degradation. The current chapter focuses on the carrier-based delivery of bioactive as a booster with advanced nanosciences, such as nanoemulsion and vesicular drug delivery systems. In addition, the chapter also elaborates patented technologies along with potential bioactive products available in the market.

Pulmonary diseases impose an immense burden on global health. Asthma, cystic and idiopathic pulmonary fibrosis, pulmonary hypertension, lung cancer, and chronic obstructive pulmonary diseases (COPD) are among the diseases that require efficient pulmonary drug delivery. Targeted-drug delivery refers to the delivery of a drug or a therapeutic agent to a certain tissue or organ; this can be achieved through pulmonary drug delivery (PDD) with nanomaterials. Nanomaterials are made from polymers, ceramics, metals, and biological materials into different sizes and structures. Nanomaterials for PDD entail nanoparticles of therapeutic ingredients, including herbalbased drugs and nanocarriers of the therapeutic bioactive substance. These types of materials used in managing pulmonary diseases are discussed in this chapter.

The pharmaceutical industry has witnessed a huge revolution in the past few decades due to the discovery of various novel drugs for the treatment of several lifethreatening ailments. However, there is a continued interest in exploring nature for inventing therapeutically active novel compounds. Among the various natural resources, plants constitute an invaluable source of bioactive molecules. Numerous studies have illustrated the exceptional therapeutic efficacy of phytochemicals against various diseases. Some of the well-known drugs, such as paclitaxel, vincristine, vinblastine, etc., which can potentially be used in cancer therapy, were first isolated from plants. Later, several other drug-active molecules, which have demonstrated promising therapeutic effects, were discovered. Despite their outstanding antimicrobial, antidiabetic, and anticancer effects in vitro, most of these molecules fail to achieve a similar effect in vivo, mainly due to their poor aqueous solubility and bioavailability. The advent of nanotechnology and the application of nano-drug delivery carriers have significantly revolutionized the biomedical industry. Numerous studies indicate the successful utilization of nanoparticles for theragnostic applications. Nanoparticles having a size of approximately 507250 nm can efficiently interact with cellular structures, eliciting desirable therapeutic effects. Apart from improving the aqueous dispersibility and stability of drugs, nanoparticles enable cell-specific as well as receptor-specific drug targeting, thereby reducing the off-target effects. Moreover, the stealthy nature of surface-modified nanoparticles, in combination with the controlled release of encapsulated drugs, enables prolonged therapeutic activity in vivo. This chapter presents an updated summary of the applications and challenges of various nano-drug carrier systems for the delivery of natural bioactive principles.

Liposomes are utilised as a delivery carrier in insulin therapy for several reasons; an enhancement in the oral absorption of insulin, the ability to selectively target insulin to the hepatic system, and prolong drug action for proper dose regimen. The hepatocytic delivery of insulin can be achieved efficiently through the insulin liposomal method. While treating diabetes with liver-targeted liposomes, it is expected that constraints will arise due to the formulation being supplied by an intravenous route. Furthermore, due to the dilute concentration of insulin in the liposomal formulation, the overall cost of the liposomal insulin would rise. The consequence of encapsulating the drug in the liposomal carrier is improved oral absorption of insulin. Drug action can be continued by giving subcutaneous liposomal insulin. Insulin remains at the site of injection, and the occurrence of a lipid matrix for subcutaneous insulin delivery raises concerns about over-improved antigenicity. The liposomal insulin sustains the role of a delivery system in understanding and treating diabetes using the hepatically targeted liposomal system. This pharmacological aspect has highlighted the role of the liver in the metabolic complications associated with diabetes mellitus.

 Aquasomes are ceramic nanoparticulate drug delivery systems, and they are utilised for the delivery of antibiotics, hormones, peptides, genes, and proteins. Structurally, aquasomes are self-assembled, consisting of three layers, where the solid core is coated with an oligomeric film. Bioactive molecules or therapeutic agents are adsorbed at the oligomeric film. The structural stability of this nanocarrier is provided by the centre core, whereas the oligomeric film provides protection against dehydration and stabilizes the active biological molecules. Active biochemical molecules with or without modification are incorporated at the oligomeric film by diffusion, adsorption, or copolymerization. It has been established that drug candidates have shown better biological activity and immune response when they are delivered through aquasomes. Insulin, poorly water-insoluble drugs, enzymes, and haemoglobin have been delivered through aquasomes successfully. Therefore, aquasomes provide a new approach to delivering a wide range of therapeutics such as vaccines, proteins, and peptides.

Being a notable form of neurodegenerative disorder, Alzheimer's disease (AD) accounts for the cognitive decline of a wide range of the population globally. Any form of dysfunction to the cholinergic system of the brain marks the onset of cognitive decline and paves the way for progressive neurodegeneration in AD. Alteration in acetylcholinesterase activity, accumulation of beta-amyloid protein, mitochondrial dysfunction, oxidative stress, and neuroinflammation are some of the marked gateways to the pathogenesis of AD. Although nature harbors a wide array of herbal cures to various gateways of cholinergic dysfunction, there exist certain restrictions to efficient delivery and therapeutic action of the phytocompounds in-vivo. Despite bearing certain reversible limitations, the application of nanoscience has successfully cleared off several barriers from the drug designing and delivery of herbal extracts and enriched the therapeutic potentiality of the medicinal plants that have been practiced extensively since time immemorial. Several forms of nanoparticles (NP) have been designed to date viz., polymeric NP, lipid-based NP, metallic NP, each having their characteristic advantage as drug carriers. In addition to advantages like high drug loading capacity, target-specific drug release, high bioavailability, etc., the ability to penetrate the Blood- Brain Barrier (BBB) non-invasively makes the nanocarriers most suitable for delivering herbal drugs targeting neurodegenerative disorders. The present chapter, therefore, discusses the therapeutic qualities of several herbal compounds targeting cholinergic dysfunction and the remarkable milestones set by nanotechnology in amplifying the potentiality of the herbal drugs in the treatment of AD.

With the rapid advances in science and technology in recent years, nanotechnology has gained much attention in all disciplines. Due to its wide applicability in various fields, researchers and academicians are showing great interest in nanotechnology nowadays. Some of its applications include neutraceuticals, nanoemulsions, nanomedicines, nanoencapsulation, and many more. Understanding and controlling matter at the nanoscale is what nanotechnology is all about. Nanomedicine is the most advanced application of nanotechnology. In simple terms, the basic definition of nanomedicine is the application of nanotechnology to repair damaged tissue. The European Medicine Agency (EMA) defines nanomedicine as the application of nanotechnology in the establishment of a medical diagnosis or the treatment/prevention of disease. It exploits the improved and often novel physical, chemical, and biological properties of materials at the nanometer scale. Nanomedicines come in various forms like nanoparticles, liposomes, nanogels, nanoemulsions, nanotubes, and many others, most of which have been approved by various agencies for their diagnostic/therapeutic utility. Nanomedicine has achieved a high success rate due to its widespread applicability and a variety of forms, although the road ahead is not easy. Therefore, even today, many argue about earlier planning to meet all the requirements. Due to the enzymes and chemicals in the gastrointestinal membrane (GI), some vitamins are poorly absorbed. Nanomedicine helps alleviate this problem while increasing the bioavailability of vitamins due to their remarkable absorption and distribution capabilities

Cancer is the second leading cause of death worldwide, with the highest morbidity and mortality rates. It is a heterogeneous disease that can occur in any organ or tissue of the body. The current report of the World Health Organization has demonstrated that approximately 1 crore of the world population is affected by different types of cancer, with leading cases of cancer occurring in an Asian population. Despite this, various pathways and proto-oncogenes are responsible for the progression of cancer. As such, it can affect both sexes. Prostate and breast cancer in men and women account for a significant part of cancer cases, respectively. Molecular targeting agents show a pivotal role in drug delivery. Natural compounds such as curcumin, resveratrol, genistein, and lycopene help heal the cancerous tissue efficiently and do not cause any side effects to the neighbouring cells. Targeting the site-specific portion with natural herbs provides better outcomes for cancer patients. A scientist develops various carrier systems for cancer to deliver the active moieties to the regions of the specific site. Delivery of medicament through carrier systems, such as liposomes, niosomes, dendrimers, solid lipid nanoparticles, and carbon nanotubes, provides better therapeutic outcomes due to its site-specific delivery pattern. Thus, various research for the treatment of cancer are currently ongoing. This chapter highlights an overview of various types of cancer barriers and conceptual information of carrier systems.

Niosomes are widely used nowadays as a novel drug delivery system. The amphiphilic nature of the niosomal drug delivery system provides an added advantage for a large number of newly discovered drugs. In this context, the bilayered structure of the niosomes helps in modifying various parameters involved in drug encapsulation. The niosomal drug delivery system also helps in altering the bioavailability, enhancing the skin permeability, and improving the drug interaction at the targeted sites. The present chapter focuses on the factors that influence niosomes formation, advantages and disadvantages of niosomal drug delivery systems, the formulation of niosomes in herbal products, their future prospects, commercial benefits as well as availability.

Infectious diseases are one of the greatest challenges of our new era. Due to their high incidence and outbreak rate, they can affect human health. Furthermore, the use of conventional drugs to treat infectious diseases is gradually being exhausted due to increasing rates of resistance. Herbal medicines and natural ingredients may also be a good resource for drug production. Several innovations, including the development of nano-drug delivery systems, have new mechanisms of action and various loadings for herbal and non-herbal treatments; this helps decrease the pathogenicity of infectious diseases. In addition, these nano-drug delivery systems provide a good opportunity to improve the efficacy of herbal and non-herbal treatments. They have also been used to deliver target medicinal agents, increase solubility, improve bioavailability, extend half-life for herbal and non-herbal treatments, increase stability, minimize adverse effects, and tissue engineering. Nanocarriers are advanced engineering tailors that control the physicochemical properties of nanoparticles for infectious diseases, leading to targeting by passive or active mechanisms. In this chapter, we highlight the advances in nanocarriers loaded with herbal and nonlherbal agents for treating infectious diseases.