Nanopharmaceutical Advanced Delivery Systems. Группа авторов

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СКАЧАТЬ 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 lipids. They can encapsulate hydrophilic drugs within bilayer lipids due to their unique structure, and in the central aqueous core, hydrophilic agents typically protect the agents against degradation. Liposomes promote pharmacokinetics of loaded pharmaceutical active agents and provide higher loading efficacy, higher biological stability, controlled release, biological compatibility, and many others; the basic structural components of liposomes, i.e., phospholipids, are amphiphilic in nature [22]. These amphiphilic lipids get dissolved with an aqueous medium, and liposomes were aggregated by increased process entropy over certain concentration [23, 24]. In early days, liposomes were described as not containing surface modifiers, but later they were modified to differ in rigidity, size, and other properties by altering the composition of the lipid [25]. The next-generation liposomes were offered with molecular targeting capabilities through the attachment of unique ligands to their surface [26]. In addition, different ligands and functional molecules are easy to incorporate, thereby offering practical applications for the delivery of labile drugs and genetic materials. Liposomes also suffer from certain drawback, like other carrier systems. The development costs and all other aspects should be considered while developing a formulation to enhance drug therapeutic efficacy. The uses of sophisticated explants and tedious manufacturing process increase the cost of production of liposomes [27, 28].

Figure 1.1 Types of liposomes. (a) Unilamellar vesicle, (b) multilamellar vesicle, (c) immunoliposome, and (d) stealth liposomes.

      1.3.2 Solid Lipid Nanoparticles

Solid lipid nanoparticles (SLNs) were introduced in 1991, which are the most conventional carrier system compared to other lipid carrier systems. Although some polymer-based nanoparticles were developed, still they have certain disadvantages such as toxicity, residual organic solvents, and processing complication [29, 30]. SLNs were incorporated into an inert solid lipid that offers sufficient stability and protection to encapsulated drugs as shown in Figure 1.2 [31, 32]. SLNs also offer unique features of a small size range micro-colloidal carrier between 50 and 1000 nm, larger surface area, higher drug loading, and potential for delivering drugs across various barriers [33-36].

      By definition, SLNs are submicron size nanoparticles composed of biocompatible and biodegradable solid lipids and are dispersed in aqueous surfactant solution; these mixtures are capable of providing a stable product for both lipophilic and hydrophilic drugs. For many years, they have become a promising platform for therapeutic drug delivery [37, 38] because they are simple, flexible, and stable for long term, have high drug loading efficacy, have potential for targeted responses [30, 31], have increased bioavailability, and do not require any special solvent and application versatility [33, 34]. SLNs for various routes of administrations such as dermal, parenteral, ocular, and rectal routes have been extensively studied and developed [39].

      1.3.3 Nanostructured Lipid Carriers System

Nanostructured СКАЧАТЬ