Lycopodium Spores: A Naturally Manufactured, Superrobust Biomaterial for Drug Delivery

Abstract

Herein, the exploration of natural plant‐based “spores” for the encapsulation of macromolecules as a drug delivery platform is reported. Benefits of encapsulation with natural “spores” include highly uniform size distribution and materials encapsulation by relatively economical and simple versatile methods. The natural spores possess unique micromeritic properties and an inner cavity for significant macromolecule loading with retention of therapeutic spore constituents. In addition, these natural spores can be used as advanced materials to encapsulate a wide variety of pharmaceutical drugs, chemicals, cosmetics, and food supplements. Here, for the first time a strategy to utilize natural spores as advanced materials is developed to encapsulate macromolecules by three different microencapsulation techniques including passive, compression, and vacuum loading. The natural spore formulations developed by these techniques are extensively characterized with respect to size uniformity, shape, encapsulation efficiency, and localization of macromolecules in the spores. In vitro release profiles of developed spore formulations in simulated gastric and intestinal fluids have also been studied, and alginate coatings to tune the release profile using vacuum‐loaded spores have been explored. These results provide the basis for further exploration into the encapsulation of a wide range of therapeutic molecules in natural plant spores.

Plant‐Based Hollow Microcapsules for Oral Delivery Applications: Toward Optimized Loading and Controlled Release

“…The observed rapid BSA release is attributed to the passage of molecules through the nanopores and micron‐sized apertures in the surface of SECs. A similar release profile was reported from natural sunflower ( H. annuus ) pollen grains and L. clavatum SECs in SGF and SIF …”

“…To optimize loading and elucidate the loading distribution of dried compounds within SECs, BSA loading into sunflower SECs was evaluated for three different initial BSA‐loading proportions, 23, 37.5, and 54.5 wt%. The loading process involves applying a vacuum to the SEC–BSA suspension leading to a reduction in the internal cavity pressure, which in turn applies a force drawing the BSA solution into the hollow SECs …”

“…So far, SECs have been explored for the encapsulation of proteins and it is suggested that their mechanical and chemical durability may facilitate the oral delivery of proteins . Interestingly, enzymes encapsulated into Lycopodium clavatum SECs have been shown to retain their functionality following their release from the SECs, thus implying the protective nature of SECs toward encapsulated proteins .…”

Inflated Sporopollenin Exine Capsules Obtained from Thin-Walled Pollen

“…Being the first line of defense, sporopollenin is equipped with various evolutionary-driven resilient properties specifically tailored for protection and endurance to stay viable for extended lengths of time. Due to these attractive properties along with a large and renewable supply, pollen grains have gained the attention of the wider scientific community and are proving to be excellent microcapsules for encapsulation applications31617. In order to address possible issues of biocompatibility and allergenicity, a protein-free microcapsule derivative known as a sporopollenin exine capsule (SEC) was developed through an extraction process that leaves only the hollow sporopollenin exine layer, which itself functions as a microcapsule and can be utilized for encapsulation applications151819202122.…”

“…However, current efforts have been focused on pollen or spores from only a small subset of plant species including Lycopodium clavatum 3151719222324 and Helianthus annus 16. Indeed, SEC process development has been limited to micrometer thick-walled pollen species with high mechanical stability which facilitates successful preservation of microarchitecture features throughout the harsh processing steps.…”