Various strategies are being developed to improve delivery and increase the biological half-lives of pharmacological agents. To address these issues, drug delivery technologies rely on different nano-sized molecules including: lipid vesicles, viral capsids and nano-particles. Peptides are a constituent of many of these nanomaterials and overcome some limitations associated with lipid-based or viral delivery systems, such as tune-ability, stability, specificity, inflammation, and antigenicity. This review focuses on the evolution of bio-based drug delivery nanomaterials that self-assemble forming vesicles/capsules. While lipid vesicles are preeminent among the structures; peptide-based constructs are emerging, in particular peptide bilayer delimited capsules. The novel biomaterial— Branched Amphiphilic Peptide Capsules (BAPCs) display many desirable properties. These nano-spheres are comprised of two branched peptides— bis(FLIVI)-K-KKKK and bis(FLIVIGSII)-K-KKKK, designed to mimic diacyl-phosphoglycerides in molecular architecture. They undergo supramolecular self-assembly and form solvent-filled, bilayer delineated capsules with sizes ranging from 20 nm to 2 microns depending on annealing temperatures and time. They are able to encapsulate different fluorescent dyes, therapeutic drugs, radionuclides and even small proteins. While sharing many properties with lipid vesicles, the BAPCs are much more robust. They have been analyzed for stability, size, cellular uptake and localization, intra-cellular retention and, bio-distribution both in culture and in vivo.
Branched amphipathic peptide capsules (BAPCs) are biologically derived, bilayer delimited, nanovesicles capable of being coated by or encapsulating a wide variety of solutes. The vesicles and their cargos are readily taken up by cells and become localized in the perinuclear region of cells. When BAPCs are mixed with DNA, the BAPCs act as cationic nucleation centers around which DNA winds. The BAPCs-DNA nanoparticles are capable of delivering plasmid DNA in vivo and in vitro yielding high transfection rates and minimal cytotoxicity. BAPCs share several biophysical properties with lipid vesicles. They are however considerably more stable-resisting disruption in the presence of chaotropes such as urea and guanidinium chloride, anionic detergents, proteases, and elevated temperature (∼95 °C). To date, all of our published results have utilized BAPCs that are composed of equimolar concentrations of the two branched sequences (Ac-FLIVI)-K-K-CO-NH and (Ac-FLIVIGSII)-K-K-CO-NH. The mixture of sizes was utilized to relieve potential curvature strain in the spherical capsule. In this article, different molar ratios of the two peptides were studied to test whether alternate ratios produced BAPCs with different biological and biophysical properties. Additionally, preparation (annealing) temperature was included as a second variable.
Branched Amphiphilic Peptides Capsules (BAPCs™) are a novel class of nano‐carriers constituted from the spontaneous co‐assembly of two unique, engineered peptide sequences. We recently reported on a thermally induced variant of BAPC™ that demonstrates promise as a vehicle for nucleic acid delivery and transcript knockdown. These BAPCs™ display a uniform size of 20–30 nm; they are easy to synthesize, stable and produce minimal immunogenic and inflammatory responses, in contrast to those commonly observed with viral and cationic lipid based approaches for gene delivery. BAPCs™ act as cationic nucleation centers allowing nucleic to wrap around them in a nucleosome like fashion, generating peptide‐nucleic complexes with sizes ranging from 80 to 200 nm. In this study, development of new and specific insect pest management methods capable of overcoming pesticide resistance and collateral off‐target killings are described. Gene silencing by feeding dsRNA to insects shows promise in this area. Here Branched Amphiphilic Peptide Capsules (BAPCs), facilitate cellular uptake of dsRNA by insects through feeding. The insect diets included dsRNA (300–400 bps) with and without complexation with BAPCs. The selected insect species come from two different Orders with different feeding mechanisms: Tribolium castaneum and Acyrthosiphon pisum. The gene transcripts tested (BiP and Armet) are part of the unfolded protein response (UPR) and suppressing their translation resulted in lethality. For Acyrthosiphon pisum, ingestion of BiP‐dsRNA associated with BAPCs led to the premature death of the aphids (t1/2 = 4–5 days) compared to ingestion of the same amounts of free BiP‐dsRNA (t1/2 = 11–12 days). Tribolium castaneum was effectively killed using a combination of BiP‐dsRNA and Armet‐dsRNA complexed with BAPCs; most dying as larvae or during eclosion (~75%). Feeding dsRNA alone resulted in fewer deaths (~30%). The results show that complexation of dsRNA with BAPCs enhanced the oral delivery of dsRNA over dsRNA alone.Support or Funding InformationPartial support for this project was provided by the Terry Johnson Cancer Center at Kansas State University and by the USDA's National Institute of Food and Agriculture through the Specialty Crops Research Initiative/Citrus Disease Research & Extension, USDA NIFA Award No. 2015‐70016‐23028 and an Institutional Development Award (IDeA) from NIGMS grant P20 GM103418.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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