Nanomaterials for Clinical Applications

Case Studies in Nanomedicines

Costas Demetzos, Natassa Pippa

• Publisher: Elsevier
• Year: 2020
• Print ISBN: 9780128167052
• eBook ISBN: 9780128168769
• Topic: Technology & Engineering
• Subtopic: Materials Science
• Index: Technology & Engineering

Nanomaterials in Clinical Medicine: Case Studies in Nanomedicines focuses on the nanomaterials that can be formulated as drug delivery vehicles, such as liposomes, micelles, nanoemulsions and nanogels. Their physicochemical, morphological, thermo-dynamical and nanotoxicological properties are analyzed with respect to the design and development of drug delivery nanosystems for the encapsulation of an active pharmaceutical ingredient and its controlled release. Each chapter covers basic properties, the nanosystem (e.g., liposomes), the added value in drug delivery and targeting, and future perspectives. Case studies and examples of how nanomaterials are being used in clinical medicine, including marketed liposomal medicines and medical utility and regimens are also included. Particular attention is given to new nanocarriers, such as elastic liposomes, lipid polymeric hybrid nanoparticles, organogel, nanofibers carbon nanomaterials, quantum dots and inorganic nanoparticles. This book is an important information source for those wanting to increase their understanding of what major nanomaterials are being used to create more effective drug delivery systems. - Summarizes the major nanomaterials used in clinical medicine, explaining how their properties make them suitable for this purpose - Explains how nanomaterials are used to create increasingly efficient drug delivery vehicles - Includes real-life examples, demonstrating how nanomaterials are being used in medical practice

Chapter one

Solid lipid nanoparticles in dermaceuticals

Indu Pal Kaur¹, Garima Sharma¹, Mandeep Singh¹, Mohhammad Ramzan¹, Joga Singh¹, Simarjot Kaur Sandhu¹ and Jaspreet Singh Gulati², ¹University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India, ²Hitech Formulations Pvt Ltd, Industrial Area 1, Chandigarh, India

Abstract

Prevalence of skin diseases is on the rise, world over and the conventional treatments available at present are unable to completely cure these diseases and meet the expectations of patients. In this regard new drug delivery approaches including solid lipid nanoparticles (SLNs) are currently being explored for their ability to deliver drug to the epidermis and the lower skin layers including dermis. SLNs and nanostructured lipid carriers (NLCs) feature several claimed benefits for topical drug delivery namely, biocompatible ingredients, sustained drug release, and adhesion to skin and occlusion with subsequent hydration of the outer skin layers. This chapter summarizes the need, evolution, mechanism of penetration, specific benefits (occlusion, adhesiveness, ultraviolet blocking, improved chemical stability), and applications of SLNs and NLCs. It also compiles the patents, case studies of successful topical delivery with these drug carriers and their use in finished marketed products available worldwide.

Keywords

Nanostructured lipid carriers; skin penetration; occlusion; adhesiveness; film formation; skin hydration; UV-blocking effects; patents; marketed products

1.1 General introduction

World Health Organization has included skin diseases as the most common noncommunicable diseases in hot and humid countries, including India; prevalence of these diseases is on the rise, world over. Skin being the largest organ that interfaces with the environment is exposed to a variety of physical [ultraviolet (UV) radiations], chemical, and microbial insults that affect its structure and function. Since significant part of skin is visible to others, any disfigurement of skin is often associated with social and psychological implications much beyond the actual disease symptoms. Global Burden of Disease survey reported skin and subcutaneous diseases as 18th leading cause of global disability-adjusted life years and 4th leading cause of nonfatal burden (Karimkhani et al., 2017). Years lived with disability from these diseases (36.4 million) are more than those caused by diabetes mellitus (29.5 million) and migraines (28.9 million) (Karimkhani et al., 2017). The global dermaceutical market (over the counter and prescription) is huge and evolving quickly indicating a global market of USD 91.40 billion in 2028 from USD 49.22 billion in 2018.

The treatments available at present are unable to completely cure various diseases of the skin and meet the expectations of patients. This is attributed to either a lack of suitable treatment/agents or poor delivery of drug agent to the appropriate layer of the skin. The outermost part (15–20 μm) of the epidermis, namely stratum corneum (SC), is the major barrier to drug absorption into the skin. The resistant envelopes of SC corneocytes and keratin microfibrils are considered as bricks, and the lipidic layers found between these cells are called as mortar. This unique arrangement is responsible for basic skin permeation resistance and reduces the passage of molecules (larger than 500 Da) through skin (Erdogan, 2009). Although drugs may diffuse into the skin via hair follicles, sebaceous glands, or sweat glands, permeation through the multiple lipid bilayers of SC remains the main pathway (Ting et al., 2004) because the former comprise only a small area of the skin. The inability of drug molecules to penetrate the SC and reach the deeper dermis layer of the skin in sufficient concentration can usually result in recurrence of several skin diseases including infections that are often not limited to the SC.

Small-sized carriers including liposomes, niosomes, aquasomes, transfersomes, elastosomes, microemulsions, nanoemulsions, self microemulsifying drug delivery system, self nanoemulsifying drug delivery system, and solid lipid nanoparticles (SLNs) are currently being explored extensively for their ability to permeate the SC and reach the lower skin layers including dermis and at times the subcutaneous tissue too. Both micrometer- and nanometer-range carriers were found effective in improving the delivery to skin. Since the drug is released gradually and over a prolonged period of time, irritancy or other side effects associated with the active ingredients, when applied in conventional formulations, are significantly reduced when incorporated into these systems, without compromising the efficacy (Castro and Ferreira, 2008). These systems not only mask the irritation and side effects of the selected agent to be delivered but also invariably improve its solubility and permeability.

1.2 Why solid lipid nanoparticles?

In 1990 the lipidic nanoparticles were invented as an alternative to traditional drug carriers such as polymeric nanoparticles and liposomes. Many questions of ability to produce at industrial level, regulatory status of excipients, and nanotoxicity rose regarding the use of these conventional nanocarriers. Such questions were addressed with the development of SLNs as an alternative. Various advantages of SLNs over polymeric nanoparticles and liposomes are elaborated later.

1.2.1 Formulation aspects

• • SLNs can be prepared without employing organic solvents. Residues of these solvents have toxic effects (Kaur et al., 2014).
• • High drug loading (~10% or more) can be achieved with SLNs versus a low drug loading of <5% in case of polymeric nanoparticles (Singh et al., 2010).
• • SLNs are reported to be stable for up to 3 years (Kakkar et al., 2011). This is an important advantage over other colloidal carrier systems.
• • Remarkable scalability and reproducibility of important properties namely, particle size and encapsulation efficiency in large (Liu et al., 2007) batches using a cost-effective high-pressure homogenization technique as the preparation procedure is again an exclusive advantage with SLNs (Albanese et al., 2012).
• • SLNs can be sterilized by autoclaving. Other nano colloidal systems are sterilized by gamma irradiation, which is not only costly and a specialized technique but may possibly lead to the formation of free radicals and subsequently toxic reaction products (Kaur et al., 2014).
• • Quantification of SLN in creams is simplified as compared to other particles. Many cream bases do not exhibit a melting peak below 100°C, which means the content of SLN in a cream can be quantified by their melting peak determined by differential scanning calorimetry.

1.2.2 Physiological aspects

• • SLNs act as drug reservoirs in various skin layers (Vyas et al., 2014) by variety of uptake mechanisms like entering into a shunt such as hair follicle, accumulating between corneocytes, and intermingling with skin lipids, or by disintegrating and merging with lipidic layers (Toll et al., 2004; Bseiso et al., 2015).
• • Depending on the produced SLN type, controlled release of the active ingredients is possible. SLNs with a drug-enriched shell show burst release characteristics whereas SLNs with a drug-enriched core lead to sustained release (Wissing and Müller, 2003b).
• • SLNs act as occlusives, that is, they can increase the water content of the skin making it more hydrated and thus more permeable (Wissing et al., 2001).
• • SLNs show a UV-blocking potential, that is, they act as physical sunscreens on their own and can be combined with molecular sunscreens to achieve improved photoprotection (Wissing and Müller, 2003b).
• • The components used to formulate SLNs are safe as compared to polymeric nano- and microparticles which may cause systemic toxicity by impairment of the reticuloendothelial system due to slow degradation of its components up to 4 weeks (Cavalli et al., 2000).

1.3 Evolution of lipidic nanoparticles from solid lipid nanoparticles to nanostructured lipid carriers

The most important parameters for evaluation of lipid nanoparticles are particle size and size distribution, zeta potential, polymorphism, degree of crystallinity, drug loading, entrapment effi...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• List of contributors
• Chapter one. Solid lipid nanoparticles in dermaceuticals
• Chapter two. Cyclodextrin-based drug delivery systems
• Chapter three. Lipid vesicles for (trans)dermal administration
• Chapter four. Stimuli-responsive nanocarriers for drug delivery
• Chapter five. Biodegradable nanomaterials
• Chapter six. Modulating the immune response with liposomal delivery
• Chapter seven. Recent advances in solid lipid nanoparticles formulation and clinical applications
• Chapter eight. Biopolymers, liposomes, and nanofibers as modified peroral drug release formulants
• Chapter nine. Grafted polymethacrylate nanocarriers in drug delivery
• Index