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Lipid-Based Nanocarriers as Drug Delivery System and Its Applications

Vikas Jain*, Hitesh Kumar, Pallavi Chand, Sourabh Jain and Preethi S

Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru, India

Abstract

Various nanotechnology platforms have received notable attention in the field of medical biology, including diagnostics and therapy. In addition, research and development of engineered multifunctional nanoparticles as drug carriers has stimulated exponential development of applications in medicine. Lipid nanocarriers have been a very promising tool for the delivery of various drugs/therapeutic agents associated with solubility-, bioavailability-, and stability-related issues. Lipid nanocarriers including liposomes, solid lipid-based systems, self-emulsifying drug delivery system, nanoemulsions, nanostructured lipid carriers, cubosomes and hexosomes, etc. are being very promising lipidic carriers to deliver several drugs, therapeutics nucleic acids, antibodies, proteins/peptides, or ligand targeted agents. Lipids-based nanocarriers have the benefit of having exciting physicochemical behaviors such as higher bioavailability, least toxicity, higher drug loading, greater drug solubility, improved targeting effect of drug, etc. compared to others nanocarriers. This chapter includes the challenges and hurdles in lipid nano-formulations and their application in drug delivery in various diseases. The chapter provides a brief description of advantage, types of lipid nanocarriers, their preparation method, characteristic properties, and characterization/evaluation methods including instrumentations and application in the nanopharmaceutical field.

Keywords: Crystalline mesophases, drug delivery system, liposome, lipid nanocarriers, nanostructured lipid carriers, nanoemulsions, self-emulsifying drug delivery system, solid lipid nanoparticles

List of Abbreviations

1.1 Introduction

Evolution and application of the nanotechnology in pharmaceutical field have brought the development of microscopic drug delivery systems, which have marked the birth of "micro age" drug delivery systems [1]. The beginning of the nano period can be dated back to the late 1970s as a result of the introduction of several nano tools known as nanoscaled medicine systems. A wide variety of colloidal drug carriers including polymer nanosphere and nano-capsules, lipid nanoparticles, liposomes, and micelles are involved in nanoscaled drug delivery systems.

Presently, the development of drugs in the industry is more difficult and challenging because of an increasing number of poorly soluble drug(s) and the lack of targeted therapies. More than 90% of the recorded compounds have water insolubilities and/or are poorly soluble, often due to low bioavailability and a wide intra- and intersubject variation and lack of dosage efficacy [2, 3]. To address these issues, drug formulators need to look for new methods and novel formulation strategies and to ensure effective treatments for vulnerable patients.

Various nanotechnology platforms have received notable attention in the field of medical biology, including diagnostics and therapy. In addition, multifunction nanoparticles as drug carriers have stimulated rapid development of medical applications. Nanoparticles also have superiorities such as increasing drug stability and preventing adverse reactions by prolonged drug release behaviors [4, 5].

Formulating drug delivery system of active compounds with poor aqueous solubility using lipid-based systems is one of the promising strategies. Lipid provides a better alternative for the delivery of various drugs that suffer from solubility-, bioavailability-, and stability-related issues. In many studies, lipid formulations have been tried to increase bioavailability and dissolution of drugs, which are water insoluble [6]. The spontaneous emulsification in aqueous media is one of the major benefits by imparting such carriers to promote delivery of poorly soluble drugs.

Various literatures reported the characteristics and essential properties, design and development, utilization, and potential applications of various lipid-based nanocarriers in drug delivery [7, 8]. The current chapter discusses various lipid-based nanocarriers such as solid-lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), vesicular nanocarriers including liposomes, nanoemulsions, self-emulsifying drug delivery system (SEDDS), and crystalline mesophases in various application pharmaceutical fields. The information on the formulation components and processing aspects has also been discussed in detail.

1.2 An Overview on Nanocarriers

In the early 1990s, solid polymers in nanoparticles consisting of non-biodegradable and biodegradable polymers having size from 10 to 1000 nm with site-specific delivery feature and regulated drug release were developed. However, the major problem encountered was the higher cytotoxicity associated with these polymers [9-11]. Therefore, lipid-derived carriers emerged as a keystone for novel formulations because of its low cytotoxicity.

In the past two decades, the development of lipid-based drug carriers has received greater attention. Lipid nanoparticles offer several potential uses in the fields of drugs delivery, clinical medicine, research, and other varied sciences. Due to their unusual dimensional dependency, lipid nanoparticles provide the opportunity to develop new therapeutics. A new prototype in drug delivery for secondary and tertiary targeting can be made possible by incorporating the drug into these nanocarriers [12].

The first liposomes were introduced by Dior in 1986 to the cosmetic market. After several years, liposomes in the form of pharmaceutical products appeared in the market. As a novel carrier, liposomes were not only technically advanced but also have gained wide public interest. There are several other concepts of formulation; for example, microemulsions, nanoemulsions, and solid particles (such as microsponge) were also explored in the last two decades. Nevertheless, these nanocarriers have not been found in wide applications and have not gained any attention like liposomes.

SLNs have certain benefits in contrast to liposomes and emulsion, e.g., protecting the active compounds from chemical oxidation and offering greater versatility in amplifying compound release [12, 13]. Furthermore, lipid nanoparticles made of solid lipid and liquid lipid were explored by different research groups, which were used on a variety of routes such as parenteral, oral, dermal, ocular, or rectal and were thoroughly characterized [14, 15]. Nowadays, modified SLNs were known as nanostructured lipid carriers (NLCs) and nanoparticles lipid drug conjugates (LDCs) [13, 16, 17]. These carrier systems were able to resolve the issues observed with conventional SLNs.

A lipid nanocarrier system provides the drug with smaller droplet sizes in solubilized form offering a large surface area, which increases the activity of pancreatic lipases for the hydrolysis of triglycerides, and this will enable the faster release of the drug. Neoral® (cyclosporin A) is a commercial product that is an excellent example of the utilization of these systems [18]. This carrier system has another advantage in that it can be used for clinical purposes because organic solvents can be avoided during the preparation process. A further advantage is that it is easy and cost-effective to produce.

1.3 Types of Nanocarriers

1.3.1 Liposomes

The most popular and well-researched nanocarriers are liposomes, which are synthetic phospholipid vesicles with a size of about 50-1,000 nm that can be loaded with a variety of drugs including hydrophilic and hydrophobic drugs. Figure 1.1 depicts it all [19]. Originally liposomes referred to as smectic mesophase are monolamellar or multilamellar spherical vesicles that include phospholipids either of animal or plant origin. Liposomes were first discovered by AD Bangham and later on described by Allison and Gregoriad [20, 21]. Liposomes are spherical vesicles composed of bilayer...