Nanobiotechnology in Diagnosis, Drug Delivery and Treatment. Группа авторов

scheme of similar colorimetric nanosensors.

      1.3.2 In Drug Delivery and Treatment

Nanotechnologies have enabled novel solutions for the treatment of various diseases. Nano‐drug delivery systems present some advantages over conventional (non‐targeted) drug delivery systems such as high cellular uptake and reduced side effects (Singh et al. 2019). Figure 1.6 represents the comparison between untargeted and targeted drug delivery systems. The development of drug delivery systems by using nanotechnology for various diseases, particularly for cancer treatment, is making revolutionary changes in treatment methods and handling side effects of chemotherapy (Zhao et al. 2018). Furthermore, nanotechnology allows for selective targeting of disease‐ and infection‐containing cells and malfunctioning cells. Nanotechnology has also opened a new era in implantable delivery systems such as those used in bone cement, nano‐needle patches, etc., which are preferable than using other modes of direction like injections and oral delivery. Therefore, nano‐based drug delivery systems have attracted a great of attention due to novel and promising properties like enhanced bioavailability and stability of the drug.

Figure 1.6 Schematic representation of comparison between untargeted and targeted drug delivery systems.

      Moreover, antimicrobials are one of the most important therapeutic discoveries in the history of medicine. Some projections suggest that by 2050 the annual deaths caused by multidrug‐resistant bacterial infections will reach up to 10 million per year (de Kraker et al. 2016). Nanotechnology provides an innovative platform to address this challenge, because of their small size and various other physical, chemical, and optical properties. As mentioned above, numerous nanomaterials are reported to have significant antimicrobial efficacies and hence such nanomaterials can be used as next‐generation antimicrobials against various multidrug‐resistant organisms and also in the treatment of different infectious diseases (Rai et al. 2012; Beyth et al. 2015; Rai et al. 2016).

      The bioavailability of a drug within the body depends on some factors like the size of the drug molecules and solubility factors (Kesharwani et al. 2018). The conventional dosage system consequently faces some challenges in reaching the target site at an appropriate dose. For example, highly water‐soluble drugs cause fluctuations in drug concentration in the body due to high disintegration properties, and also result in quicker clearance of the drug from the bloodstream. However, some medicines are fat‐soluble and when such drugs are taken in the form of conventional dosage, they face bioavailability difficulties. Similarly, patients suffering from chronic diseases like diabetes need to take painful insulin injections regularly. Likewise, cancer patients regularly have to undergo powerful chemotherapy, which involves quite severe side effects as the anticancer drugs target cancer cells and normal cells equally. Therefore, proper platforms to deliver the drugs at targeted sites without losing their efficacies, and while limiting the associated side effects, are highly required (Mura et al. 2013).

      Many novel technologies for developing effective drug delivery systems came into existence in this context, among which nanotechnology platforms for achieving targeted drug delivery are gaining prominence. Research in this field includes the development of drug nanoparticles, polymeric and inorganic biodegradable nanocarriers for drug delivery, and surface engineering of carrier molecules (Senapati et al. 2018). These nanocarriers help in solubilizing the lipophilic drugs, protecting fragile drugs from enzymatic degradation, pH conditions, etc., and targeting specific sites with triggered release of drug contents.

      To date, a wide range of nanomaterials enlisted above has been developed and used for applications in nano‐drug delivery. There are many reports on the usage of metallic nanoparticles in drug delivery and diagnostic applications. It mainly includes the applications of silver, gold, and iron‐based superparamagnetic nanoparticles as nanocarriers for controlled and targeted delivery of potential drugs and genes for enhanced clinical efficacy. In addition, nanosuspensions or nanodispersions, which are theoretically considered the simplest form of nanomedicine, contain two specific components, the active pharmaceutical ingredients nanoparticle and the adsorbed surface stabilizer(s), which have been also effectively used in the treatment of various diseases (Adeyemi and Sulaiman 2015).

Similarly, polymeric nanoparticles or nanopolymer manufactured through the chemical conjugation of active pharmaceutical ingredients and a water‐soluble polymer have been used to develop a polymer‐drug or polymer‐protein conjugate or pro‐drug compounds which are further used in the treatment of a wide range of diseases. The chemical degradation releases the active pharmaceutical ingredients into the bloodstream or the site of disease (Tong et al. 2009). Likewise, various other nanocarrier systems like liposome, SLN, dendrimers, quantum dots, etc., are promisingly used in the development of efficient drug delivery systems for potential management of diseases (Liang et al. 2014; Núñez et al. 2018; Mitragotri and Stayton 2019). The role of such nano‐based drug delivery systems in the treatment of various diseases has been briefly discussed here.

      1.3.2.1 Diabetes

      Silica nanoparticles have been used in drug delivery applications for years, as they can be adjusted for continuous or triggered drug release (Bharti et al. 2015). Delivery of insulin across intestinal Caco‐2 cells using silica nanoparticles was reported. Silica nanoparticles, due to high surface area and selective absorption, can be extensively used in drug delivery systems (Bharti et al. 2015). Polymeric nanoparticles have been harnessed for targeted drug delivery and protection of nucleic acids. Interleukin (IL)‐10 and IL‐4 entrapped in polymeric nanoparticles were delivered to white blood cells to reduce the T cell response against native islet cells in prediabetic animal models. It was observed that the polymeric nanoparticles were useful in diabetic treatment as it inhibited the development of diabetes in 75% of the animal models (Singh et al. 2019).

      1.3.2.2 Cancer

      Porous silica nanoparticles have emerged as an efficient delivery system for cancer therapy. Targeted drug therapy requires zero release before reaching the target site (Bharti et al. 2015). Targeted delivery of Doxorubicin (DOX) using silica nanoparticles coated with PEG have been reported. For the study, 120 mg kg⁻¹ of nanoparticles were injected on a weekly basis for a period of three weeks to a KB‐31 xenograft model. The results of the study showed 85% inhibition of tumor by DOX‐loaded silica nanoparticles in comparison to DOX drug. A study reported curcumin‐containing liposomes conjugated with synthetic RNA aptamer (Apt‐CUR‐NPs) to target epithelial cell adhesion molecule (EpCAM) protein which is observed in colorectal adenocarcinoma. The Apt‐CUR‐NPs depicted enhanced bioactivity of curcumin (CUR) after 24 hours compared to free CUR. Apt‐CUR‐NPs also showed increased binding to HT29 colon cancer cells and cellular uptake. Comparative study of in vitro induced cytotoxicity of free CUR and Apt‐CUR‐NPs in HT29 cell line demonstrated more cytotoxicity of Apt‐CUR‐NPs in comparison to totally free CUR (cellular viabilities about 58% and 72%, respectively) (Rabiee et al. 2018).

      1.3.2.3 Psoriasis

      Psoriasis is a distinctive chronic inflammatory disease with a strong genetic makeup. Srisuk et al. (2012) evaluated permeability of Methotrexate (MTX)‐entrapped deformable liposomes and devised lipid vesicle from phosphatidylcholine (PC) and oleic acid (OA), and compared with MTX‐entrapped conventional liposomes synthesized using PC and cholesterol (CH) by thin‐film hydration method. MTX entrapped in PC: CH was observed to be more stable in size and loading. Although, MTX‐entrapped PC: OA liposomes increased the skin permeability characterized with higher absorption and flux of MTX diffused across or accumulated in the epidermis and dermis layers of porcine skin (Srisuk et al. 2012; Chandra et al. 2018).

      Pinto et al. (2014) also developed and assessed the potential of nanostructured lipid carriers (NLCs) loaded with MTX