Micro- and Nanotechnologies-Based Product Development

Neelesh Kumar Mehra, Arvind Gulbake, Neelesh Kumar Mehra, Arvind Gulbake

• Publisher: CRC Press
• Year: 2021
• ISBN:
  9781000422351
• Edition: 1
• Topic: Medicine
• Subtopic: Biotechnology in Medicine

This book provides comprehensive information of the nanotechnology-based pharmaceutical product development including a diverse range of arenas such as liposomes, nanoparticles, fullerenes, hydrogels, thermally responsive externally activated theranostics (TREAT), hydrogels, microspheres, micro- and nanoemulsions and carbon nanomaterials. It covers the micro- and nanotechnological aspects for pharmaceutical product development with the product development point of view and also covers the industrial aspects, novel technologies, stability studies, validation, safety and toxicity profiles, regulatory perspectives, scale-up technologies and fundamental concept in the development of products.

Salient Features:

• Covers micro- and nanotechnology approaches with current trends with safety and efficacy in product development.

• Presents an overview of the recent progress of stability testing, reverse engineering, validation and regulatory perspectives as per regulatory requirements.

• Provides a comprehensive overview of the latest research related to micro- and nanotechnologies including designing, optimisation, validation and scale-up of micro- and nanotechnologies.

• Is edited by two well-known researchers by contribution of vivid chapters from renowned scientists across the globe in the field of pharmaceutical sciences.

Dr. Neelesh Kumar Mehra is working as an Assistant Professor of Pharmaceutics & Biopharmaceutics at the Department of Pharmaceutics, National Institute of Pharmaceutical Education & Research (NIPER), Hyderabad, India. He received ' TEAM AWARD ' for successful commercialisation of an ophthalmic suspension product. He has authored more than 60 peer-reviewed publications in highly reputed international journals and more than 10 book chapter contributions. He has filed patents on manufacturing process and composition to improved therapeutic efficacy for topical delivery. He guided PhD and MS students for their dissertations/research projects. He has received numerous outstanding awards including Young Scientist Award and Team Award for his research output. He recently published one edited book, ' Dendrimers in Nanomedicine: Concept, Theory and Regulatory Perspectives ', in CRC Press. Currently, he is editing books on nano drug delivery-based products with Elsevier Pvt Ltd. He has rich research and teaching experience in the formulation and development of complex, innovative ophthalmic and injectable biopharmaceutical products including micro- and nanotechnologies for regulated market.

Dr. Arvind Gulbake is working as an Assistant Professor at the Faculty of Pharmacy, School of Pharmaceutical & Population Health Informatics, at DIT University, Dehradun, India. He has authored more than 40 peer-reviewed publications in highly reputed international journals, four book chapters and a patent contribution. He has received outstanding awards including Young Scientist Award and BRG Travel Award for his research. He is an assistant editor for IJAP. He guided PhD and MS students for their dissertations/research projects. He has successfully completed extramural project funded by SERB, New Delhi, Government of India. He has more than 12 years of research and teaching experience in the formulation and development of nanopharmaceuticals.

Section B

Bioactive Delivery Systems

5 Pharmaceutical and Biomedical Applications of Multifunctional Quantum Dots

Devesh Kapoor

Dr. Dayaram Patel Pharmacy College

Swapnil Sharma, Kanika Verma, and Akansha Bisth

Banasthali Vidyapith

Yashu Chourasiya

Smriti College of Pharmaceutical Education

Mayank Sharma and Rahul Maheshwari

SVKM’s NMIMS

DOI: 10.1201/9781003043164-5

Contents

5.1 Introduction

5.2 History of QDs

5.3 Types of QDs

5.4 Synthesis of QDs

5.4.1 Organic-Phase Method/Organometallic Chemistry Method

5.4.2 Water-Phase Method/Aqueous Solution Method

5.4.3 Hydrothermal and Microwave-Assisted Irradiation Methods

5.4.4 Laser Ablation Techniques for QDs

5.4.5 Molecular Beam Epitaxy (MBE) and Nanopatterning for QDs

5.5 Properties of QDs

5.6 Biomedical Applications of QDs

5.6.1 In Vivo Cell Imaging

5.6.1.1 Synaptic Neurotransmission

5.6.1.2 Single Protein Tracking

5.6.1.3 Cell Tracking and Migration

5.6.2 In Vitro/Ex Vivo Cell Imaging

5.6.3 Tissue Imaging

5.6.4 Diagnostic Tool for Detection of Diseases

5.6.5 Development of Diagnostic Test Systems

5.6.6 Biosensors/Biomarkers for Detection of Mutation, Multiplexed Target and miRNA Detection

5.6.7 Drug Delivery/Carrier for Treatment

5.6.7.1 Ocular Diseases

5.6.7.2 Cardiovascular Diseases

5.6.7.3 Neurological Disorders

5.6.7.4 Hepatic Diseases

5.6.7.5 Antibiotic-Resistant Infection

5.6.7.6 Tumours

5.6.7.7 Renal Diseases

5.6.7.8 Others

5.6.8 Cell Labelling

5.7 Conclusion

References

5.1 Introduction

Conventional formulations developed by pharmaceutical industries are in abundance, though with limited efficacy, poor permeation, decreased bioavailability and toxicity (Uehara et al. 2010). Nanotechnology is a tool for delivering drugs at specific target sites using intelligent and smart nanocarriers having well-defined sizes and shapes (Lalu et al. 2017; Tekade et al. 2017). Nanostructured materials possess the ability to bridge the gap between molecular and bulk levels and therefore create new avenues for a wide range of applications in biology, electronics and optoelectronics (Maheshwari et al. 2015; Sharma et al. 2015; Maheshwari et al. 2018; Moondra et al. 2018). Based on particle size, these nanostructures can be categorised as zero-dimensional or quantum dots (QDs), one-dimensional or quantum wires, and two-dimensional or quantum wells (Bera et al. 2010).

QDs, also known as semiconductor nanocrystals, pertain to unique electronic and optical properties, including multiplexed capabilities, long-term photostability, high signal brightness, simultaneous excitation of multiple fluorescence colours and size-tunable light emission (Jin et al. 2011). QDs are nanometre-sized semiconductor structures with dimensions smaller than the de Broglie wavelength (Mandal and Chakrabarti 2017). Nanometre size increases the particle surface area-to-volume ratio, which further enables surface modifications to ameliorate reactivity, solubility and biocompatibility (Wagner et al. 2019). QDs are proven to be integrated with a range of applications in biomedical sciences, including fluorescent assay for drug discovery, bioimaging, detection of disease, intracellular reporting and protein tracking (Rosenthal et al. 2011). Moreover, these nanometre-sized QDs also overcome severe toxicity, decrease effective dose and increase sensitivity (Wagner et al. 2019).

5.2 History of QDs

At the end of 1970, during the crisis of petroleum, researchers aimed at discovering alternatives for solar energy conversion. This provokes the investigators to synthesise semiconductor crystals in solution and screens their optoelectronic properties. Meanwhile, they observed blueshift with a decrease in nanocrystal size and explained quantum confinement effect. Typically, the studies on QDs were initiated in physics and then emerged through medical and technical fields. Of note, quantum oscillator, transistor, multispectral fluorescent dye imaging, filters, detectors, data analysis technique and QD light imaging device are some inventions in the field of physics (Bera et al. 2010; Efros and Nesbitt 2016). Interestingly, the outstanding and unique properties of QDs make them novel drug delivery and targeting approaches (Figures 5.1 and 5.2).

FIGURE 5.1 Hierarchy in the history of QDs. Hierarchical moments marked in the journey of development of QDs by global universities including its application in medicine as imaging system, diagnostic tools and optical labelling.

FIGURE 5.2 Historical representation of QDs. The figure highlights the contribution of eminent scientists globally for historical development of QDs possessing outstanding and unique properties that make them a novel drug delivery material in targeting and delivery.

5.3 Types of QDs

These are nanoscale man-fabricated crystals that can convert light spectrum into diverse colours. According to the size of these QDs, every dot emits a different colour. QDs can be classified into distinct types based on their composition and structure, such as core-type QDs, core-shell QDs and alloyed QDs (Liu and Su 2014). A typical structure of QDs is presented in Figure 5.3.

FIGURE 5.3 Structure of a typical QD. Diagrammatic representation of a basic QD with core (semiconductor such as CdSe or CdTe), shell (such as ZnS), amphiphilic polymers (such as PEG) and target molecules such as peptides or antibodies.

5.4 Synthesis of QDs

5.4.1 Organic-Phase Method/Organometallic Chemistry Method

The organometallic chemistry method is considered as the most crucial method for the synthesis of regular and uniform core-structured monodisperse QDs with high quantum yield in non-polar organic solvents (Aswathi et al. 2018). Different sizes of QDs can be obtained by varying temperature and reaction time conditions. In general, bis(trimethylsilyl)selenium ((TMS)₂Se) and Me₂Cd are two profusely used organometallic precursors. Monodisperse CdSe can be obtained based on the pyrolysis of organometallic reagents by injection into a hot coordinating solvent between 250°C and 300°C. The adsorption of ligand such as tri-n-octylphosphine oxide (TOPO) leads to annealing of cores in coordinating solvents (Jin et al. 2011).

5.4.2 Water-Phase Method/Aqueous Solution Method

The aqueous solution method is a cost-effective and eco-friendly procedure of QD synthesis. The technique has direct applications in biological research without the involvement of the ligand exchange procedure. In general, glutathione (GSH), 3-mercaptopropionic acid (3-MPA) or other hydrosulfyl-containing materials are the commonly used ligands for the production of CdTe QDs in aqueous solution. In addition to this, ionic perchlorates such as Al₂Te₃ and Cd(ClO)₄·6H₂O are used as the precursors. Thiol-capped CdTe QDs were the first synthesised aqueous dispersed QDs; however, they showed low quantum yields, poor stability and broad size distribution when compared with the QDs produced by the organometallic method (Jin et al. 2011; Aswathi et al. 2018).

5.4.3 Hydrothermal and Microwave-Assisted Irradiation Methods

Hydrothermal and microwave-assisted irradiation methods are used to produce QDs with high quantum yields and narrow size distribution. Moreover, these methods also reduce the reaction time and surface defects generated during the growth process of QDs due to high pressure. In brief, all reaction reagents are heated at high temperatures up to supercritical temperature into the hermetic container. In the microwave-assisted irradiation method, microwave irradiation is considered as a heating source which aids in optimising synthesis conditions. An increase in heat from this system produces homogenous QDs with high yield (17%) (Jin et al. 2011; Aswathi et al. 2018). Different synthesis methods of QDs are presented in Figure 5.4.

FIGURE 5.4 Various approaches for the synthesis of QDs. Diagrammatic representation of multiple synthesis approaches considered during the development of QDs.

5.4.4 Laser Ablation Techniques for QDs

This method is reported as a clean technique...