Advances in Nanotechnology-Based Drug Delivery Systems
Edited by
Anupam
Das Talukdar
Department of Life Science and Bioinformatics, Assam University, Silchar, Assam, India
Satyajit Dey Sarker
School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK
Jayanta Kumar Patra
Research Institute of Integrative Life Sciences, Dongguk University, Goyang-si, South Korea
Series Editor
Jayanta Kumar Patra
Elsevier
Radarweg 29, PO Box 211, 1000 AE Amsterdam, Netherlands
The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, United Kingdom 50 Hampshire Street, 5th Floor, Cambridge, MA 02139, United States
Copyright © 2022 Elsevier Inc. All rights reserved.
No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions
This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein).
Notices
Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary.
Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility.
To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein.
ISBN: 978-0-323-88450-1
For Information on all Elsevier publications visit our website at https://www.elsevier.com/books-and-journals
Publisher: Matthew Deans
Acquisitions Editor: Sabrina Webber
Editorial Project Manager: Leticia M. Lima
Production Project Manager: Prasanna Kalyanaraman
Cover Designer: Mark Rogers
Typeset by Aptara, New Delhi, India
3.3
4 Stability of therapeutic nano-drugs during storage and transportation as well as after ingestion in the human body
Veerababu Nagati, Swathi Tenugu, Anil K. Pasupulati
4.1 Introduction
4.2 Factors contributing to the stability of nanoparticles
4.3 Influence of the type of nanoparticle and core material on the stability
4.4 Improving the stability of nanoparticles by appropriate preparation methods
4.5
4.6 Contribution of stabilizers in the storage of functional nanoparticles
4.7 Ingestion of nanoparticles and their fate
4.8 Transportation of therapeutic nanoparticles
4.9
5
Ashitha Jose, Sreekanth K., Radhakrishnan E.K.
5.1
5.2
5.3
5.4
5.5
6 Clinical potential of nanotechnlogy as smart therapeutics: A step toward targeted drug delivery
Priyanka Saha, Subhankar Bose, Md Noushad Javed, Amit K. Srivastava
6.1 Inception of nanobiotechnology
6.2
6.3
6.5
and COVID-19 outbreak: Recent highlights into the nanotechnology
8
Ahmed Farhan Shallal, Muhammad Akram, Rasim Farraj Muslim, Mustafa Nadhim Owaid, Omar Qahtan Yaseen, Muhammad A. Chishti 8.1
8.6
8.7
8.8
8.9
Anuradha Pandit, Yasmin Begum, Priyanka Saha, Snehasikta Swarnakar
9.7
9.8
10 Nanonutrition- and nanoparticle-based ultraviolet rays
Najwa Ahmad Kuthi, Norazah Basar, Sheela Chandren
(UVR)
10.6 Inorganic UV filters
10.7 Lipid- and surfactant-based nanoparticles for broadband
10.8 New avenues in UV protection
10.9 Biological and environmental impacts of sunscreen ingredients
11 Drug and gene delivery by nanocarriers: Drug delivery process, in brief, using different oxides such as zinc, iron, calcium, polymeric, peptides, and in-vitro drug delivery process by silicon oxide (SiOx) and titanium dioxide (TiO2) nanodots (NDs)
Shubhro Chakrabartty, AlaaDdin Al-Shidaifat, Ramadan Al-Shdefat, M.I. Alam, Hanjung Song
11.2.3.6.1
11.2.3.8
11.2.3.9 Preparation of peripheral blood smear
11.2.3.9.1 RBC Detection and size measurement
11.2.4 Result and discusion
11.2.4.1
11.2.4.2
Priyanka Saha
15
Minakshi Puzari, Pankaj Chetia 15.1
15.7
15.8
15.9
Sabyasachi Banerjee, Utsab Chakraborty, Subhasis Banerjee, Sankhadip Bose, Arijit Mondal, Anupam Bishayee
17.1.2.5
17.2.2
17.2.2.1
17.2.2.2
Omar Qahtan Yaseen, Rasim Farraj Muslim, Muwafaq Ayesh Rabeea, Mustafa Nadhim Owaid
Lata Sheo Bachan Upadhyay, Sonali Rana, Nikhil Kumar 20.1
20.3
20.4
20.7 Hydrogels
20.8 Bioceramics
20.9 Different doped elements in biomaterial used for tissue engineering
20.10 Challenges and future perspectives
21 Nanocarriers: A boon to the drug delivery systems 255
Lata Sheo Bachan Upadhyay, Nikhil Kumar
21.1 Introduction
21.1.1 Background of drug delivery system development
21.1.2 Why nanocarriers as DDS? 557
21.2 Type/classes of nanocarriers
21.2.1 Biologically derived nanocarrier
21.2.1.1 Liposomes-based DDS
21.2.1.2 Protein-based nanoparticle 564
21.2.2 Chemically derived nanocarrier 565
21.2.2.1 Nanocrystals 565
21.2.2.2 Polymeric nanogels 566
21.2.2.3 Dendrimers 567
21.3 Synthesis methods for nanocarriers 568
21.3.1 Methods of liposome preparation
21.3.1.1 Mechanical dispersion methods
21.3.1.1.1 Sonication
21.3.1.1.2 French pressure cell: extrusion 569
21.3.1.1.3 Freeze-thawed liposomes 569
21.3.1.1.4 Lipid film dehydration rehydration method 569
21.3.1.2 Solvent dispersion methods 570
21.3.1.2.1 Ethanol injection
21.3.1.3 Detergent removal methods
21.3.2 Methods of preparation of protein nanoparticles
21.3.2.1 Complex coacervation 570
21.3.2.2 Emulsion/solvent extraction
21.3.3 Drug nanocrystals preparation 571
21.3.3.1 Top-down technique 571
21.3.3.2 Bottom-up technique 571
21.3.3.2.1 Solvent evaporation method 571
21.3.3.2.2 Hydrosol technique 571
21.3.3.2.3 Freeze-drying technique 572
21.3.4 Polymeric nanogels synthesis 572
21.3.4.1 Emulsion-based methods 572
21.3.4.1.1 Inverse emulsion method/polymerization 572
21.3.4.1.2 Membrane emulsification 572
21.3.4.2 Solution polymerization 573
21.3.4.3 Bulk polymerization or conversion of macroscopic gels to nanogels 573
21.3.5 Dendrimer synthesis methods 573
21.3.5.1 Divergent methods 574
21.3.5.2 Convergent methods 574
21.4 Conclusion 574 References 575
22
Shraddha Chauhan, Anita Tirkey, Lata Sheo Bachan Upadhyay
22.1.5.4
22.1.5.5
23.3
23.4
23.5
Contributors
Arghya Adhikary WAST INSPIRE Faculty, Centre for Research in Nanoscience and Nanotechnology (CRNN) University of Calcutta, Kolkata
Najwa Ahmad Kuthi Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia, Johor Bahru, Johor, Malaysia
Muhammad Akram Department of Eastern Medicine, Government College University, Faisalabad, Pakistan
Ramadan Al-Shdefat Department of Pharmaceutical Sciences, Faculty of Pharmacy, Jadara University, Irbid, Jordan
AlaaDdin Al-Shidaifat Department of Nanoscience and Engineering, Centre for Nano Manufacturing, Inje University Gimhae, Republic of Korea
M.I. Alam Department of Physiology, HIMSR, Jamia Humdard, New Delhi
Vaidegi Balaji Department of Biotechnology, School of BioSciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India
Sabyasachi Banerjee Department of Pharmaceutical Chemistry, Gupta College of Technological Sciences, Asansol, West Bengal, India
Subhasis Banerjee Department of Pharmaceutical Chemistry, Gupta College of Technological Sciences, Asansol, West Bengal, India
Norazah Basar Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia, Johor Bahru, Johor, Malaysia; Centre of Lipids Engineering & Applied Research (CLEAR), Ibnu Sina Institute for Scientific and Industrial Research, Universiti Teknologi Malaysia, Johor Bahru, Johor, Malaysia
Yasmin Begum Infectious Diseases & Immunology Division, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata, West Bengal, India
Shamee Bhattacharjee Dept. of Zoology, West Bengal State University, Berunanpukuria, Malikapur, Kolkata
Anupam Bishayee Lake Erie College of Osteopathic Medicine, Bradenton, FL, USA
Subhankar Bose Division of Cancer Biology & Inflammatory Disorder, CSIRIndian Institute of Chemical Biology, Kolkata, WB, India; Academy of scientific and innovative research (AcSIR), Ghaziabad, UP, India
Sankhadip Bose Department of Pharmacy, Sanaka Educational Trust’s Group of Institutions, Durgapur, West Bengal, India
Shubhro Chakrabartty Department of Nanoscience and Engineering, Centre for Nano Manufacturing, Inje University Gimhae, Republic of Korea
Utsab Chakraborty Department of Pharmaceutical Chemistry, Gupta College of Technological Sciences, Asansol, West Bengal, India
Sheela Chandren Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia, Johor Bahru, Johor, Malaysia
Shraddha Chauhan Department of Biotechnology, National Institute of Technology, Raipur, Chhattisgarh, India
Pankaj Chetia Department of Life Sciences, Dibrugarh University, Dibrugarh, Assam, India
Muhammad A. Chishti Department of Basic Clinical Sciences, Faculty of Eastern Medicine, Hamdard University, Karachi, Pakistan
Sudip Choudhury Department of Chemistry, Assam University, Silchar, Assam, India
Diana Costa Univ Coimbra, Department of Pharmaceutical Technology, Faculty of Pharmacy, Azinhaga de Santa Comba, Pólo III - Pólo das Ciências da Saúde, Coimbra, Portugal
Kuheli Deb Department of Chemistry, Assam University, Silchar, Assam, India
Namrata Dwivedi Biotechnology Centre, Jawaharlal Nehru Krishi Vishwa Vidyalaya (JNKVV), Jabalpur, Madhya Pradesh, India
Radhakrishnan E.K. School of Biosciences, Mahatma Gandhi University, Kottayam, Kerala, India
Ana Figueiras Univ Coimbra, Department of Pharmaceutical Technology, Faculty of Pharmacy, Azinhaga de Santa Comba, Pólo III - Pólo das Ciências da Saúde, Coimbra, Portugal; Univ Coimbra, REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy, Azinhaga de Santa Comba, Pólo III - Pólo das Ciências da Saúde, Coimbra, Portugal
Sunayana Goswami Department of Zoology, Biswanath College, Assam, India
Ivana Jarak Univ Coimbra, Department of Pharmaceutical Technology, Faculty of Pharmacy, Azinhaga de Santa Comba, Pólo III - Pólo das Ciências da Saúde, Coimbra, Portugal
Md Noushad Javed Department of Pharmaceutics, Jamia Hamdard, New Delhi, India
Ashitha Jose School of Biosciences, Mahatma Gandhi University, Kottayam, Kerala, India
Sreekanth K. School of Biosciences, Mahatma Gandhi University, Kottayam, Kerala, India
Nikhil Kumar Department of Biotechnology, National Institute of Technology, Raipur, Chhattisgarh, India
Nikhil Kumar Department of Biotechnology, National Institute of Technology, Raipur, Chhattisgarh, India
Gayathri Mahalingam Department of Biotechnology, School of BioSciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India
Deba P. Mandal Dept. of Zoology, West Bengal State University, Berunanpukuria, Malikapur, Kolkata
Arijit Mondal Department of Pharmaceutical Chemistry, M.R. College of Pharmaceutical Sciences & Research, Balisa, Ashoknagar, West Bengal, India
Arijit Mondal Department of Pharmaceutical Chemistry, M.R.College of Pharmaceutical Sciences & Research, Balisa, Ashoknagar, India
Rasim Farraj Muslim Department of Environmental Sciences, College of Applied Sciences, University of Anbar, Anbar, Iraq
Rasim Farraj Muslim Department of Environmental Sciences, College of Applied Sciences, University Of Anbar, Anbar, Iraq
Veerababu Nagati School of Life Sciences, University of Hyderabad, Hyderabad, India
Lutfun Nahar Laboratory of Growth Regulators, Institute of Experimental Botany
ASCR & Palacký University, Olomouc, Czech Republic
Lutfun Nahar Laboratory of Growth Regulators, Institute of Experimental Botany
ASCR & Palacký University, Olomouc, Czech Republic
Sanjoy Singh Ningthoujam Department of Botany, Ghanapriya Women’s College, Dhanamanjuri University, Imphal, Manipur, India
Mustafa Nadhim Owaid Department of Environmental Sciences, College of Applied Sciences, University of Anbar, Anbar, Iraq; Department of Heet Education, General Directorate of Education in Anbar, Ministry of Education, Anbar, Iraq
Mustafa Nadhim Owaid Department of Heet Education, General Directorate of Education in Anbar, Ministry of Education, Anbar, Iraq; Department of Environmental Sciences, College of Applied Sciences, University Of Anbar, Anbar, Iraq
Mustafa Nadhim Owaid Department of Heet Education, General Directorate of Education in Anbar, Ministry of Education, Anbar, Iraq; Department of Environmental Sciences, College of Applied Sciences, University Of Anbar, Anbar, Iraq
Anuradha Pandit Infectious Diseases & Immunology Division, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata, West Bengal, India
Anil K. Pasupulati School of Life Sciences, University of Hyderabad, Hyderabad, India
Saurav Paul Department of Chemistry, Assam University, Silchar, Assam, India
Paramita Paul Department of Pharmaceutical Technology, University of North Bengal, Darjeeling, India
Minakshi Puzari Department of Life Sciences, Dibrugarh University, Dibrugarh, Assam, India
Muwafaq Ayesh Rabeea Department of Applied Chemistry, College of Applied Sciences, University of Anbar, Anbar, Iraq
Sonali Rana Department of Biotechnology, National Institute of Technology, Raipur, Chhattisgarh, India
Andreza Maria Ribeiro Department of Engineering and Material Sciences, University of Federal of Paraná (UFPR), Curitiba, Brazil; Univ Coimbra, Department of Pharmaceutical Technology, Faculty of Pharmacy, Azinhaga de Santa Comba, Pólo III - Pólo das Ciências da Saúde, Coimbra, Portugal
Priyanka Saha Division of Cancer Biology & Inflammatory Disorder, CSIR-Indian Institute of Chemical Biology, Kolkata, WB, India
Satyajit Dey Sarker Centre for Natural Products Discovery (CNPD), School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, James Parsons Building, Liverpool, United Kingdom
Ahmed Farhan Shallal Medical Laboratory Science Department, College of Science, University of Raparin, Sulaymaniyah, KRG, Iraq
Hanjung Song Department of Nanoscience and Engineering, Centre for Nano Manufacturing, Inje University Gimhae, Republic of Korea
Amit K. Srivastava Division of Cancer Biology & Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata, West Bengal, India
Snehasikta Swarnakar Infectious Diseases & Immunology Division, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata, West Bengal, India
Swathi Tenugu School of Life Sciences, University of Hyderabad, Hyderabad, India
Anita Tirkey Department of Biotechnology, National Institute of Technology, Raipur, Chhattisgarh, India
Lata Sheo Bachan Upadhyay Department of Biotechnology, National Institute of Technology, Raipur, Chhattisgarh, India
Francisco Veiga Univ Coimbra, Department of Pharmaceutical Technology, Faculty of Pharmacy, Azinhaga de Santa Comba, Pólo III - Pólo das Ciências da Saúde, Coimbra, Portugal; Univ Coimbra, REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy, Azinhaga de Santa Comba, Pólo III - Pólo das Ciências da Saúde, Coimbra, Portugal
Omar Qahtan Yaseen Department of Heet Education, General Directorate of Education in Anbar, Ministry of Education, Anbar, Iraq
Nanotechnology: Scopes and various aspects of drug delivery
Shamee Bhattacharjeea, Deba P. Mandala, Arghya Adhikaryb
aDept.
of Zoology, West Bengal State University,
Berunanpukuria, Malikapur, Kolkata, bWAST INSPIRE Faculty, Centre for Research in Nanoscience and Nanotechnology (CRNN) University of Calcutta, Kolkata
1.1 Introduction
The term “nanotechnology” was first reflected in the lecture entitled as “There is plenty of room at the bottom,” conveyed by Richard Feynman in 1959 (Nordmann, 2008). Nanotechnology can boost the enhanced provisions in the field of communications, chemistry, engineering, robotics, physics, biology and medicine. It is a widely accepted wing of future technology that has provided a breakthrough in customization of the materials at the scale of atoms and molecules to the nanoscale range, viz, Nanoparticles. The characteristic feature of the nanoparticles is thought to be <100 nm in at least one dimension and this facilitates the profound uptake of nanoparticles by cells as compared to the larger micro-molecules (Zein et al., 2020). The use of nanoparticles in drug delivery is envisioned to overcome the key challenges posed by the delivery of large sized molecules such as poor bioavailability, poor solubility, non-specificity, toxicity etc (Patra et al., 2018). In addition to drug delivery, nanoparticles are also gaining increasing prominence in the field of diagnostics. Nanomaterials such as those composed of precious metals like gold, silver, cadmium, quantam dots etc., have also beautifully strengthened the imaging approaches beyond fluorescence microscopy. Unlike the existing fluorescent probes, proteins or small molecule dye, nanotech probes are capable of producing signals that are manifold brighter and more promising in terms of stability. These can be excited with just blast of photon lasers and do not disintegrate like organic dye. The bioimaging approaches of nanotechnology is serving as a supplementary tool for clinical diagnosis as well as drug-delivery devices (Ramos et al., 2017).The various proposed models of nanoparticles employed in biomedical research and drug delivery system are inorganic nanoparticles, polymeric nanoparticles, solid-lipid nanoparticles, liposome, nanocrystals, nanotubes, dendrimers, nanogels, etc. Nanotechnology is now evolving itself to accomplish “targeted delivery” even though the ease of targeting them to specific cell types or subcellular sites or targeted protein extends from challenging to impossible (Friedman et al., 2013). Targeting can be active or passive. In the former, antibodies or ligands are conjugated with the drug delivery system which targets them to the cellular sites expressing the corresponding antigens or receptors. Passive targeting is achieved when the drug-carrier conjugate reach the target site depending on pH, temperature, etc. (De Jong and Borm, 2008).
https://doi.org/10.1016/B978-0-323-88450-1.00001-6
The evolution in the field of nanotechnology empowers us to apply this technology in the field of cancer research and treatment in the form of nanomedicine and nanotherapy. In the context of nanomedicine, nanoparticles in the range of 10–1000 nm are a double-edged swords in the armamentarium because of their ability to act as cytotoxic drugs against cancer as well as widely employed as vehicles or carriers for other anticancer agents or biomolecule. The whole nanoparticle system is known as smartdrugs or theranostics which can be applied in the treatment, prevention or diagnosis of diseases (Patra et al., 2018). The main objectives of nanomedicine research include: increasing target specificity of drugs and optimizing delivery, amelioration of toxicity to normal cells without compromising its therapeutic effects, enhancing biocompatibility, thus leading to the development of novel safe medicines. The challenges in nanodrug delivery systems is related to the basic prerequisites for designing new nanomedicines, like inclusion and release into the cell or system, stability and shelf life of the desired formulation, biocompatibility, bio-distribution and targeting. Moreover, when used only as a medicine, the possibility of toxicity resulting from the residual material after delivery is a concern. One of the approaches to reduce toxicity issues is to use natural products in the synthesis of drug loaded nanoparticles. By reducing the use of hazardous chemicals in the synthesis of nanoparticles, this green chemistry approach has the potential to resolve the toxicity issues of nano based drug delivery (Lam et al., 2017). In this chapter, we provide an overview of the various nano-based drug delivery systems and some important phytochemical based nanomedicines.
1.2
Design of nanotechnology – rooted drug delivery systems
Drug delivery through nanoparticles is aimed to mediate precise delivery of drug at the site of disease, to facilitate the uptake of drugs with low aqueous solubility (Kakkar et al., 2017) and enhance drug bioavailability. Thus, nanoparticles are designed to carry adequate dose of a drug which would remain in the circulation for optimum duration and prevent drug degradation or its premature elimination, improve drug uptake by cells via endocytosis or adsorption, should not evoke any immunogenic response and preferably involve a cost-effective synthetic process (Kakkar et al., 2017). A heap of anticancer drugs including paclitaxel, doxorubicin, 5-fluorouracil and dexamethasone have been profitably formulated using nanomaterials (Jabir et al., 2012). Following are some important classes of nanoparticles.
1.3 Liposomes
Liposomes, one of the earliest and widely used nanocarriers, are assembly of amphipathic phospholipid bilayer that encompasses an aqueous core. Thus, liposomes can carry both molecules with diverse solubility properties. Due to its compositional similarity with plasma membranes of cells, a distinct advantage of liposomes is their
biocompatibility. In addition, liposomes also prevent the degradation of drugs by encaging them. The first description of such spontaneously forming liposomal structures dates back as early as 1965 (Bangham et al., 1965) and the first demonstration of the use liposomes in drug delivery dates back to 1971 (Gregoriadis and Ryman, 1971). Since then, technological advances have led to the development of improved and more efficient liposomes. For example surface modifications of liposomes by coating them with polyethylene glycol (PEG) overcame the problem of rapid clearance of first generation liposomes by the mononuclear phagocyte system which lead to an increased half lives of liposomes in the circulation. Such PEG coated liposomes aar termed “stealth” liposomes (Jokerst et al., 2011).
Another challenge in liposome mediated drug delivery is optimization of the retention and release of the entrapped molecule. Incorporation of cholesterol and sphingomyelin in the lipid bilayer was found to reduce drug leakage (Senior and Gregoriadis, 1982; Cullis and Hope, 1980). The release of the liposomal contents on reaching the destination can be manipulated by using triggers such as pH changes, light (Gerasimov et al., 1999), heat (Papahadjopoulos et al., 1973), ultrasound (Huang and MacDonald, 2004). Further, in order to increase the specificity of drug delivery by liposomes, ligands specific to target tissues are attached to lipsomes in order to make them active-targeting liposomes (Sapra et al., 2005). Ligand-targeted liposomes is an expanding field of research and a few such liposomes are undergoing clinical developments such as a HER-2 targeting antibody conjugated liposome loaded with doxorubicin which specifically targets HER-2 expressing breast cancer cells (Miller et al., 2016).
Several liposome-based formulations are already used in the clinic for the treatment of various disorders. The first liposome encapsulated chemotherapeutic agent to obtain regulatory clearance was Doxil which was approved by FDA for the treatment of ovarian cancer. Subsequently, many other liposomal formulations like Daunoxome, Myocet, Onivyde etc., have been approved for the treatment of cancer. Similarly, antifungal liposomal formulations such as Amphotec and Ambisome have facilitated the treatment of fungal infections. Liposomes are also used as vaccine delivery systems for several diseases. For e.g. the Covid-19 mRNA vaccines are delivered using liposomes (Fanciullino et al., 2021). Liposomal vaccines are also available for influenza (Inflexal), shingles (Shringrix), hepatitis (Epaxal), etc. (Wang et al., 2019).
In addition, liposomes are being extensively used as cargo for the delivery of a wide variety of phytochemicals. Despite exhibiting immense bioactive potential in research laboratories, the use of phytochemicals in the clinics is severely limited largely because of issues with their solubility, stability and bioavailability (Giri, 2019). Thus, in order to ensure efficient delivery of phytochemicals and protection from external environment (such as cellular pH and enzymes) encapsulation of phytochemicals within liposomes seems to be a promising technique. A recent review has discussed the improved therapeutic potential of phytochemicals such as curcumin, thymoquinone, piperine, lycopene, resveratrol and many others when their delivery is mediated by liposomes (Singh et al., 2019). A few such phytochemical-based liposomal formulations which are at various phases of clinical developments are vincristine sulfate liposome injection (Trade Name: Marqibo) which has been approved by FDA
Advances in Nanotechnology-Based Drug Delivery Systems for treating philadelhia chromosome negative acute lymphocytic leukemia (ALL) (FDA, 2021), liposomal 9- nitrocampothecin (Trade Name: L9-NC) for Ewing’s sarcoma (NCT00492141), liposomal curcumin (Lipocurc) for treating solid tumors (NCT02138955).
1.3.1 Microemulsions
The terminology of “microemulsion” draws its existence to two Faculties of Chemistry at Cambridge University, namely Professor T.P. Honar and J.H. Shulman in their 1943 Nature article entitled “Transparent Water-in-Oil Dispersions: the Oleopathic HydroMicelle” (Hoar and Schulman, 1943). Microemulsions are thermodynamically stable systems usually composed of oil, water and surfactant with or without combination of a cosurfactant (Majuru and Oyewumi, 2009). Physically they are clear and bear uniformity in all orientations, that is isotropic, with droplet size between 5 to 100 nm. The stability of such system comes from the fact that the major components are immiscible and that of the presence of surfactant.
Microemulsions can be used to deliver hydrophilic and lipophilic drugs including drugs that are relatively insoluble in both aqueous and hydrophobic solvents (Madhav and Gupta, 2011). Though due to toxicological possibilities arising due to the presence of surfactants these systems are not preferred for intravenous systems however ocular and topical administration of drugs in microemulsion systems has gained popularity (Madhav and Gupta, 2011).
Oral Delivery: Enhanced absorption leading to greater clinical potency coupled with lower drug toxicity is the benefits offered by microemulsion formulations in oral formulation. Favorably drugs like steroids, hormones, diuretics, and antibiotics can have regulated delivery with the use of microelumsion formulations (Jadhav et al., 2006). Use of food grade materials such as medium chain glycerides (approved by US FDA) for improved intestinal absorption of drugs have led to development of microemulsions incorporated medium chain glycerides (Jadhav et al., 2006). Studies have shown that chemotherapeutic agent Paclitaxel’s oral absorption (Yang et al., 2004) as well as suatained release (Kang et al., 2004) can be achieved using self-microemulsifying drug delivery system. Neoral is an oral formulation of cyclosporine uses microemulsion systems for increased absorbtion and greater efficacy (Jadhav et al., 2006).
Topical route: Microemulsions in topical drug delivery system are probably the most abundantly studied and used with success stories with drugs like apomorphine, lidocaine, ketoprofen etc. (Jadhav et al., 2006). Microelmulsion formulations with drugs like (Jadhav et al., 2006). Interestingly ampiphilic antioxidant ascorbyl palmitate (skin protection azelaic acid, methotrexate, aceclofenac, vinpocetine, triptolide, fluconazole, etc., have also yielded positive results in topical administration against ultraviolet induced free radicals) aws found to be successful due to higher penetration through the skin and biologically present in pharmacologically effect amount due to microelumsion delivery systems.
Topical immunization involving plasmid DNA incorporated into ethanol-influorocarbon microemulsion proved effective in elicitation of the immune system (Jadhav et al., 2006).
Ocular route: microemulsions have also found hope and promise in ocular medications. With such carrier systems increase water solubility of drugs makes for ophthalmologic more bioavailable as for example dexamethasone (Jadhav et al., 2006).
Intravaginal route: In this section contraceptive- spermicidal agents, drugs against sexually transmitted pathogens as well as AIDS are being explored with huge success (Jadhav et al., 2006).
Others: microemulsion based drug delivery is also being explored using parental routes, periodontal routes as well as nasal and buccal routes (Jadhav et al., 2006).
1.3.2 Solid lipid nanoparticle (SLN)
These nanodelivery systems are though chemically lipid and in water or other immiscible liquids like microemulsions but here the lipid is in solid phase. The term Solid Lipid Nanoparticle was introduced by Muller et al in 1993 (Muller et al., 1993). These sytems were less toxic and allowed more regulated release as compared to the most other nano-delivery systems. The lipid solid may be in the form of crystals or shapes like disc-like shape or flat ellipsoidal contour, with the drug attached mostly to the surface instead of the core (Muller et al., 1993). Though most of the SLNs have hovered around cancer therapeutics, their application in other domains like antibiotics and treatment of the central nervous systems are also popular (Muller et al., 1993). Anticancer therapeutics using SLN include taxanes, 5-flurouracil, cisplatin/oxaplatin, etc. Use of these systems encompasses target specificity using peptides, antibodies or even folate residues (usually over expressed in cancerous cells). Folate residues tagged SLN with payloads like irinotecans or combinations of resveratrol and ferulic acid has proven to be successful in laboratory scale treatments.
On the other hand CNS acting drugs are faced with the challenge of overcoming the blood brain barrier and thus SLN here too offers targeted delivery options when conjugated with cellular ligand motifs like angiopep-2 or antibodies like antibodies (Muller et al., 1993). Some studies using dual antibodies for double stage targeting like BBB cells with 83–14 MAb and glioblastoma cells with Anti-EGFR yielded increased cytotoxicity towards cancer cells (Kuo and Lee, 2016). Notable success is with that of albumin bound paclitaxel, Abraxane, whose sales have surpassed the billion dollar mark in recent times (Muller et al., 1993).
CNS acting drugs zidovudine and saquinavir have also gained success in laboratory studies.
SLN based antiviral and antibiotic deliveries are also being explored to overcome multidrug resistant situations. On the other hand SLN based delivery of Azole group of fungicides and other lipid loving antiparasitic molecules are also being explored. SLN systems have been demonstrated to increase bioavailability of otherwise effective phytochemicals like curcumin.
Increased bioavailability and better pharmacokinetic profile of various drugs have been achieved using SLN systems in oral, parental and subcutaneous routes of administration (Muller et al., 1993).
