Nanopharmaceutical Advanced Delivery Systems. Группа авторов
drugs for individual patients using the following technologies for safe and effective therapy [19].
Figure 3.1 Basic personalized drug delivery approach.
Figure 3.2 Response rates of patients to a major drug for a selected group of therapeutic areas.
The primary objective of a personalized and customized drug delivery system is to analyze the clinical pharmacogenetics of each and every individual to distinguish the responders and nonresponders in the patient population for a particular drug and also the differences in risks of adverse drug reactions among the same population with the same drug [20]. This information provides the best choice of drug for a particular individual or a group of patients for better therapy with lesser adverse drug reactions and maximum likeliness of efficacy. It is essential to test a patient to identify whether the individual is responsive or nonresponsive to the particular agent or a class of therapeutic agents. Similarly, it paves an opportunity to understand whether the individual is prone to adverse effects and its degree of risk/benefits [21].
A patient may or may not show therapeutic response to a particular drug or even its adverse effects. There exist many reasons such as drug–drug interactions, drug causing hypersensitive reactions, allergic reactions, wrong dosing, and medicament fault. On the other hand, the patient’s genetic susceptibility to pathogen remains ambiguous for the drugs’ inappropriate response. Various genes are shown to associate to a specific drug molecule showing no response or fluctuations in the therapeutic effects, and some may also lead to ADRs (adverse drug reactions) [22]. For example, 5-lipoxygenease (ALOX-5) directly influences the production of leukotrienes, helps in treating asthma; clinically it is proved that patients with gene expression of inactive alleles of 5-lipogenase are not responsive to ALOX-5 inhibitor. Likely drug metabolizing enzyme CYP2D6 having two non-expressive alleles cannot perform its functional metabolism of codeine to morphine and no activity of analgesia is showcased [23].
In 2017, Arellano et al. conducted a study on multiple ADRs associated with genetic polymorphism. CYP2D6 is a polymorphic isozyme having more than 100 allelic variants; it is suspected to have a higher degree of risk causing ADR in individuals using the commonly prescribed therapeutic agents such as analgesics, beta adrenergic antagonists, anti-arrhythmic, antipsychotics, antidepressants, and cough suppressants that are metabolized to an extent of 25% by CYP2D6 due to a higher dose of drug accumulation in systemic circulation. Likewise, the lack of this enzyme leads to poor effect of drug response in prodrugs like tramadol [24].
The study of the genetic relations associated with ADRs is more important; therefore, recognizing the pathophysiologic mechanism of the drug reactions helps to identify safer drugs and biomarkers in the future for prevention, diagnosis, and treatment of patients developing ADRs. Studies associated with genetics in relation to ADR are quite challenging due to their heterogeneity in clinical demonstrations and broad range of therapeutic agents causing ADRs [25]. From the above-discussed examples and the needs of the patients for better therapy, the transformation of pharmacogenomics and pharmacogenetics in the field of advancing medicines must be enhanced by creating a patient genetic database, providing the healthcare professionals with detailed information about the predisposition of the therapy for a particular disease and drug [26]. The nongenomic factors acculturate a significant and better composition of data to increase the exactness of the patient therapy, which includes clinical and environmental factors. The advancing field of pharmacogenomics is now highly attractive and is now newly encouraged by the poly-omics tech. A gathered determination is necessary for the healthcare professionals to equip the implications of pharmacogenomic technique essentially and fundamental research in the area of clinical healthcare community, commercial enterprises, and regulatory bodies [27].
3.3 Customized Nanotools and Their Benefits
The applications of gene therapy in approaching the target disease by genetic material engineered modification or substitution at the site of gene expression in the target cells are vectored by the nanotools [28]. The advances in nanoparticles as an emerging technique are a promising tool for clinical therapy utilizing their nature of shape, size, surface, biological deportment, and properties. Gene-based therapy is showcased as an emerging advanced significant strategy for the treatment of many diseases associating the specific gene responsible for the following diseases: tumors, neurodegenerative diseases, autoimmune disease, hypercholesterolemia, hemophilia, many microbial caused diseases, etc. The strategy involves introducing a gene into a particular target pathogen tissue causing modification or substitution at the endogenous gene expression by employing nanoparticle dosage form as a vehicle for delivery, preventing and curing the progression of that disease. The major challenges of this particular delivery of genomic material to the target site by equipping nanotech are the encapsulation efficacy of the genomic material in the nanodosage form, degradation in systemic circulation, endocytosis and endosomal escape by the target tissues, efficacy of the delivery system, pharmacological toxicity, and nanoparticle stability [29]. To bypass these many hinders, there are researchers forecasting many different types of nanocarriers for genetic material delivery such as lipoid-based nanoformulations, polymeric nanoparticles, and inorganic nanovehicles [30]. In 2016, Farris et al. developed and formulated a clinical nanocarrier for delivering a gene. A multinucleotide vaccine synthesizes a protein antigen in the area neighboring the antigen presenting cell leading to immunological responses. The key components (DNA) of the formulated vaccine delivery system can economically produce and has better storage and handling property than the components present in the other major peptide-based vaccines [31].
Various types of nanoformulations (Table 3.1) as carriers opting the advantage of their morphology, function, and composition are mentioned below:
Table 3.1 An overview of the nanotools.
| Customized nanotools | Size range (nm) | Description | Advantages | Disadvantages |
|---|---|---|---|---|
| Liposomes | 50 to 100 | A spherical vesicle containing minimum of one lipid bilayer encapsulating the aqueous core contain the drug molecules serve as a carrier. | Increase the efficacy and therapeutic index of the drugReduce toxicityFlexibility to couple to the target specific ligandsBiocompatible, biodegradable, non-immunogenic for both systemic and nonsystemic administration | Low solubilityLesser half-lifeLipids undergo reactions like oxidation and hydrolysis to a specific extentLeakage and fusion of the vesiclesEconomically high in costLess stable |
| Solid lipid nanoparticle (SLN) | 50 to 1000 | Globular structure vesicles encapsulated by monolayers of phospholipids containing dissolved or dispersed drug in the core media. | Control and/or target drug release and enhance bioavailabilityExcellent biocompatibilityHigh and enhanced drug contentEasy to scale up and sterilizeBetter control over release kinetics of encapsulated compoundsLiable drugsChemical protection of labile incorporated compoundsCan be subjected to commercial sterilization procedures. |
Particle |