Two-level delivery systems for oral administration of peptides and proteins based on spore capsules of Lycopodium clavatum

Abstract

Two-level delivery systems for oral administration of therapeutic proteins and peptides were developed.

Human blood plasma catalyses the degradation of Lycopodium plant sporoderm microcapsules

“…It was found that after 96 h incubation in SBF the magnitudes of changes were extremely diminished, which confirms the functional role of human blood plasma in SDMCs degradation. This correlates well with the literature that reports the physical degradation of SECs in human/rat blood and plasma but not in SBF or serum 9,17 .…”

“…However, broken SDMCs were seen to be altered into irregular pieces with aspect ratios between 0.5 and 0.6. Hence, it can be inferred that the observed population shift in terms of aspect ratio following blood plasma incubation is a result of partial degradation rather than complete breakage, which would agree with previously reported scanning electron microscopy images of partially degraded SECs that were treated in rat blood for 30 min 17 .…”

“…Most spore/pollen cell cytoplasm, which is rich in nutrients and active substances including proteins, vitamins, carbohydrates and pigments, can be extracted 8,12,14 . These SDMCs are naturally produced by plants and are abundant in large quantities 15–17 . In addition, they are mainly composed of sporopollenin, an extremely robust mix of biopolymers that are resilient to harsh chemical (e.g., a variety of strong acids and alkalis) and physical conditions (e.g., high pressure or mechanical stress) 12 .…”

“…However, much of the researches pertain to harsh conditions that bear no correlation to biological systems – a particularly important point for potential biological applications of sporopollenin-based microcapsules such as drug delivery considering its biocompatibility, renewability and low cost. In addition, the natural Lycopodium and the extracted sporopollenin exine capsules (SECs) can withstand the harsh environment of the stomach, which would facilitate the oral administration and controlled drug release into the gastrointestinal (GI) tract 8,9,13,16,17,41–43 . It was recently reported that SECs composed mainly of sporopollenin, could permeate through intestinal walls and decompose in the blood to release their contents within 30–60 mins 9,17,25,44 .…”

“…In addition, the natural Lycopodium and the extracted sporopollenin exine capsules (SECs) can withstand the harsh environment of the stomach, which would facilitate the oral administration and controlled drug release into the gastrointestinal (GI) tract 8,9,13,16,17,41–43 . It was recently reported that SECs composed mainly of sporopollenin, could permeate through intestinal walls and decompose in the blood to release their contents within 30–60 mins 9,17,25,44 . Further, it was suggested that enzymes present in human plasma would play a role in the degradation of SECs 9,45 .…”