Recent Progress in Diatom Biosilica: A Natural Nanoporous Silica Material as Sustained Release Carrier

Abstract

A drug delivery system (DDS) is a useful technology that efficiently delivers a target drug to a patient’s specific diseased tissue with minimal side effects. DDS is a convergence of several areas of study, comprising pharmacy, medicine, biotechnology, and chemistry fields. In the traditional pharmacological concept, developing drugs for disease treatment has been the primary research field of pharmacology. The significance of DDS in delivering drugs with optimal formulation to target areas to increase bioavailability and minimize side effects has been recently highlighted. In addition, since the burst release found in various DDS platforms can reduce drug delivery efficiency due to unpredictable drug loss, many recent DDS studies have focused on developing carriers with a sustained release. Among various drug carriers, mesoporous silica DDS (MS-DDS) is applied to various drug administration routes, based on its sustained releases, nanosized porous structures, and excellent solubility for poorly soluble drugs. However, the synthesized MS-DDS has caused complications such as toxicity in the body, long-term accumulation, and poor excretion ability owing to acid treatment-centered manufacturing methods. Therefore, biosilica obtained from diatoms, as a natural MS-DDS, has recently emerged as an alternative to synthesized MS-DDS. This natural silica carrier is an optimal DDS platform because culturing diatoms is easy, and the silica can be separated from diatoms using a simple treatment. In this review, we discuss the manufacturing methods and applications to various disease models based on the advantages of biosilica.

Introduction

In chemotherapy, exploring new drugs and reducing their side effects by improving their bioavailability based on various formulations, such as pills and creams, are essential [1,2]. Many drugs may randomly damage organs other than those targeted during administration, owing to poor solubility and lack of target function, a complication requiring alleviation in various pharmaceutical fields [3,4,5]. Therefore, drug delivery system (DDS) studies investigate effectively delivering drugs with various characteristics beyond the physiological barrier in the body through various delivery vehicles [4,5].

DDSs have been continuously developed since the introduction of the concept of sustained release systems in the 1950s, and numerous DDS platforms have been developed to overcome the physiological barriers in various administration routes [6]. As a representative example, DDS platforms, such as collagen-based oral delivery pills, are resistant to digestive enzymes, and patches are used for sustained drug delivery through the skin [7]. Additionally, nano- and microscale DDS platforms for highly functional delivery systems have been developed in recent decades. A decrease in the DSS size improves various functions, such as solubility of poorly soluble drugs, evasion of the body’s immune system, cell permeability, and passive cancer targeting based on enhanced permeability and retention effects [8,9].

Sub-microscale DDS platforms are currently developed primarily through chemical synthesis methods based on inorganic materials, such as silica and metals, or various organic materials, such as polymers and lipids [10]. Among them, the mesoporous silica-based DDS (MS-DDS), which primarily has a nanosized porous structure on its surface, has been recognized as safe by the US Food and Drug Administration and has been evaluated as an effective DDS platform for various drug deliveries [11]. MS-DDS is currently evaluated as an excellent oral DDS owing to its porous structure-based controlled release ability and high drug solubility for poorly soluble drugs [12]. Among MS-DDS platforms, artificially synthesized mesoporous silica nanoparticles (MSN) have the advantage of nanosized mesoporous carriers; however, they have commercialization limitations, such as cytotoxicity and scale-up, owing to various toxic substances used during their production (Figure 1) [13]. Hence, researchers are seeking novel MS-DDS platforms that overcome the disadvantages of synthetic MS-DDS.

The frustule of diatoms in various water systems has been an attractive natural MS-DDS, similar to biosilica. Diatoms, the microalgae in various aquatic environments, are single-celled autotrophic protists, with a size of 1–100 μm, surrounded by a double silica wall. They contain chlorophyll and can produce nutrients via photosynthesis [14,15]. In addition, diatoms are believed to contribute up to 25% of global primary productivity, equivalent to that of tropical rain forests [16,17]. Furthermore, they are essential primary producers in aquatic systems, accounting for approximately 40% of marine primary productivity, and are reportedly essential in the ocean silicon cycle [18,19]. Diatom cell walls comprise silica, which has a complex and unique structure depending on the species and is used to identify the species in morphological classification. To date, approximately 18,000 and 2260 species have been reported worldwide [20] and in Korea [21], respectively.

Each biosilica diatom varies in size and shape (e.g., disk-, rod-, and linear-shaped) depending on the species, and the MSN-like porous nanostructures are formed by unique enzymes involved in silica fixation and synthesis [13,22]. These features enable controlled drug release even during long-term digestion, facilitating their use in developing oral formulations [23,24]. Moreover, most carriers developed to date are formed through artificial synthesis; however, this biosilica is reported to be naturally formed during the growth of organisms and has excellent biodegradability in the body [25,26]. In addition, diatoms can be easily cultured and purified to obtain biosilica of uniform size, and according to recent MS-DDS studies, these natural silica carriers can be considered excellent oral DDS platforms [23,27]. In this review, the latest study trends and the performance of biosilica in various drug administration methods are analyzed. Similarly, we discuss the potential of biosilica for developing an effective oral DDS platform.

Figure 1. Various structures of the two types (synthetic/natural) of mesoporous silica-based drug delivery system (MS-DDS). Reproduced with permission from [28], published by the National Center for Biotechnology Information, 2015, and [29], published by Springer, 2012.

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Lim, H.; Seo, Y.; Kwon, D.; Kang, S.; Yu, J.; Park, H.; Lee, S.D.; Lee, T. Recent Progress in Diatom Biosilica: A Natural Nanoporous Silica Material as Sustained Release Carrier. Pharmaceutics 2023, 15, 2434. https://doi.org/10.3390/pharmaceutics15102434

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