Mesoporous calcium carbonate crystals as novel vectors for in ovo delivery

Campbell, J.C., 2023. Mesoporous calcium carbonate crystals as novel vectors for in ovo delivery. PhD, Nottingham Trent University.

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Abstract

The continuing increase in population demands for an affordable food and protein source, farmed poultry provides a means to combat this. Current growth rates within modern broiler lines have continually increased due to intense genetic selection; due to this, the developing embryo cannot solely rely on the contents of the egg for its successful growth. In ovo feeding (IOF) is the nutrient supplementation of the egg and acts to improve the energy-status of late-term chick embryos. Current methodologies to provide IOF are based upon mechanical injection, which can result in the reduced structural integrity of the eggshell and leaves the developing embryo susceptible to bacterial infection. Moreover, delivered nutrients are unprotected, and there is a lack of protective delivery vectors.

The permeation of food-grade carrier gels is proposed as an alternative approach to IOF via injection. An investigation into the surface properties of the eggshell is presented, focusing on shell permeability and porosity. This permeation is dependent upon the polarity of the carrier gel. With this, an injection-free delivery method is proposed utilising the spontaneous permeation of polypropylene glycol (PPG) through the eggshell. IOF is demonstrated through the delivery of fluorescently labelled model bioactives. Delivery vectors dispersed throughout the PPG carrier gel act as hosts and an approach to protect sensitive bioactive material.

Both vaterite CaCO3 crystals and their layer-by-layer templated microgels are novel inorganic and organic structures which have attracted significant scientific interest as drug delivery vectors owing to their biological relevance, low-cost production, and highly tuneable properties. This work seeks to develop delivery vectors based on vaterite crystals and biopolymer microgels for non-invasive IOF, and to aid in the delivery of micro- and nano-encapsulated nutrients or other compounds of interest.

Vaterite crystals (diameter of 0.5-20 m) can be loaded with model nutrients such as food-grade macromolecular dextrans and small molecule cobalamin (vitamin B12) via co-synthesis, reaching up to 8 and 1% w/w, respectively. Neutral dextran (DEX) and its charged derivatives (carboxymethyl- (CM) and diethylaminoethyl (DEAE)-DEX) were utilised. The molecular weight and charge of DEX does not affect the crystal size, but drastically influence the crystal porosity. Neutral and CM-DEX can stabilise vaterite against the recrystallisation to non-porous calcite. Vitamin B12 does not affect the vaterite morphology.

The formulation of sixteen types of vaterite-templated biopolymer-based microgels is investigated utilising four polycations (poly-L-lysine (PLL), protamine (PR), dextran amine (DA) and collagen (COL)) and four polyanions (hyaluronic acid (HA), chondroitin sulfate (CS), dextran sulfate (DS) and heparin sulfate (HS)). Stable microgels are formed from all polyanions paired with PLL and PR, whereas those paired with DA and COL undergo dissolution or disaggregation. Formation of the microgels has been correlated with the stability of the respective polyelectrolyte complexes at increased ionic strength. All formed microgels shrink upon template dissolution and the degree of shrinkage increased in the series of polyanions HS < DS < CS < HA. The same trend is observed for the adhesion of microgels to the surface upon which they are formed. The biopolymer molecular weight and charge also governs the microgel stability and internal structure. Neutral and charged DEX, as well as silver nanoparticles (AgNPs) can be encapsulated into microgels via pre-loading (co-synthesis with vaterite templates) or post-loading (adsorption to formed microgels). The loading mechanism is governed by the mechanical entrapment of cargo, as well as electrostatic interactions, where the components of charge and the capping agent of AgNPs play a role.

The findings of this thesis open new routes for the design of, and encapsulation within, CaCO3-based vectors. Such vectors may aid in the preservation of activity, protection, and the controlled release of necessary bioactive compounds for chick development. The novel permeation-based IOF approach demonstrates the universal delivery of bioactive compounds - both free and encapsulated - and its potential to replace IOF via injection.

Item Type: Thesis
Creators: Campbell, J.C.
Contributors:
NameRoleNTU IDORCID
Volodkin, D.Thesis supervisorPHY3VOLODDorcid.org/0000-0001-7474-5329
Vikulina, A.Thesis supervisorSST3VIKULA02UNSPECIFIED
Cave, G.Thesis supervisorCHP3CAVEGWVorcid.org/0000-0002-4167-1332
Date: February 2023
Rights: This work is the intellectual property of the author, and may also be owned by Nottingham Trent University. You may copy up to 5% of this work for private study, or personal, non-commercial research. Any re-use of the information contained within this document should be fully referenced, quoting the author, title, university, degree level and pagination. Queries or requests for any other use, or if a more substantial copy is required, should be directed in the owner(s) of the Intellectual Property Rights
Divisions: Schools > School of Science and Technology
Record created by: Linda Sullivan
Date Added: 07 Nov 2023 14:56
Last Modified: 30 Jul 2024 09:22
URI: https://irep.ntu.ac.uk/id/eprint/50309

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