Applications of Alginate-Based Nanomaterials in Enhancing the Therapeutic Effects of Bee Products

Abstract

Since the ancient times, bee products (i.e., honey, propolis, pollen, bee venom, bee bread, and royal jelly) have been considered as natural remedies with therapeutic effects against a number of diseases. The therapeutic pleiotropy of bee products is due to their diverse composition and chemical properties, which is independent on the bee species. This has encouraged researchers to extensively study the therapeutic potentials of these products, especially honey. On the other hand, amid the unprecedented growth in nanotechnology research and applications, nanomaterials with various characteristics have been utilized to improve the therapeutic efficiency of these products. Towards keeping the bee products as natural and non-toxic therapeutics, the green synthesis of nanocarriers loaded with these products or their extracts has received a special attention. Alginate is a naturally produced biopolymer derived from brown algae, the desirable properties of which include biodegradability, biocompatibility, non-toxicity and non-immunogenicity. This review presents an overview of alginates, including their properties, nanoformulations, and pharmaceutical applications, placing a particular emphasis on their applications for the enhancement of the therapeutic effects of bee products. Despite the paucity of studies on fabrication of alginate-based nanomaterials loaded with bee products or their extracts, recent advances in the area of utilizing alginate-based nanomaterials and other types of materials to enhance the therapeutic potentials of bee products are summarized in this work. As the most widespread and well-studied bee products, honey and propolis have garnered a special interest; combining them with alginate-based nanomaterials has led to promising findings, especially for wound healing and skin tissue engineering. Furthermore, future directions are proposed and discussed to encourage researchers to develop alginate-based stingless bee product nanomedicines, and to help in selecting suitable methods for devising nanoformulations based on multi-criteria decision making models. Also, the commercialization prospects of nanocomposites based on alginates and bee products are discussed. In conclusion, preserving original characteristics of the bee products is a critical challenge in developing nano-carrier systems. Alginate-based nanomaterials are well suited for this task because they can be fabricated without the use of harsh conditions, such as shear force and freeze-drying, which are often used for other nano-carriers. Further, conjunction of alginates with natural polymers such as honey does not only combine the medicinal properties of alginates and honey, but it could also enhance the mechanical properties and cell adhesion capacity of alginates.

Honey and propolis for wound healing

“…9,17,18 or with modified formulations as honey chitosan-based 19 or alginate-based hydrogel. 20 While propolis topical dressing 21 or its extract was used in either ointment formulation. 22 The topical application of propolis extract gel increases the expression of FGF-2 and fibroblasts within the traumatic ulcer healing process, 23 absolute ethanolic extract propylene glycol preparation dressing 24 or even wound spray 15,24 since these api products contain compounds with anti-bacterial, anti-oxidant, anti-inflammation, immunomodulation activity as well as collagen matrix production.…”

“…69 Just wound develops, platelets and neutrophils infiltrate the injury site initiates mediator cytokines mediators 54 and create contact with exposed collagen and extracellular matrix (ECM) components to form a fibrin clot. 64 Immunomodulatory action of honey 20,37,64 and propolis 37,67 is widely discussed since successful api-treatment of a broad range of wound types particularly those chronic infected forms 49 for wounds with impaired healing, including delayed acute injuries and chronic injuries 70 which often stems from a dysregulated immune response initiated or exacerbated by existing comorbidities, multiple tissue injury or wound contamination 64 especially diabetic foot. 24 70-73 where diabetic patients, it have shown that honey can reduce serum TNF-α, IL-6, IL-1ß and TGF-ß by inhibiting NF-Kß.…”

“…66 , where nanomaterials with various characteristics improve the therapeutic efficiency of bee products especially for wound healing and skin tissue engineering. 20 Adding nanoparticles to the dressing matrix or using nanoparticles to deliver drugs and cytokines to promote wound healing has proven to be effective. 8 Fabrication of biomaterials with different structures and forms such as films, hydrogel (e.g.…”

“…88 Another advantages of electro-spun nanofibers, sponge, foam that including a small diameter, high porosity, narrow diameter distribution, gas permeation, and high-specific surface to area ratio. 6,89 Various nanoscale strategies were explored for targeting different phases of wound repair 66 where these nanomaterials exhibit intrinsic properties beneficial therapeutic materials for wound treatment (natural as honey, propolis) 10,20,69,90 or employed as delivery vehicles (e.g., silver, gold, zinc) 88 for effective therapeutic agents. Nanoparticle properties increase the probability of biological interaction and injury penetration in films, foams, hydrogels, hydrocolloids, contact layers, and multilayer form dressings.…”

“…Nanoparticle properties increase the probability of biological interaction and injury penetration in films, foams, hydrogels, hydrocolloids, contact layers, and multilayer form dressings. 69,91 Honey and/or propolis was studied in nanofabrication as honey chitosan-based, 19 alginate-based hydrogel, 20 propolis chitosan-based, 92 honey-propolis-engineered collagen peptides, 10 organic-based methanolic pomegranate peel extract, 93 polyvinyl alcohol 94 or propolis nanoparticle. 72 Nanoparticle wound dressing promotes new angiogenesis and tissue regeneration and wound contraction.…”