Abstract
Introduction
Eradicating HIV/AIDS by 2030 is a central goal of the World Health Organisation. However, patient compliance with most approved HIV/AIDS treatments is low due to the complexity of drug dosing. The development of a simple, long-term formulation can be an effective way to overcome this challenge. Our formulation is an enzyme-responsive self-assembling low molecular weight D or L-peptide hydrogelator, namely phosphorylated (naphthalene-2-ly)-acetyl-diphenylalanine-lysine-tyrosine-OH (NapFFKY[p]-OH), to which zidovudine is conjugated covalently via an ester linkage. This forms a powder that can be readily dissolved in aqueous buffer to create an injectable solution.
Aims/Objectives
To understand the macroscopic properties of gels and the relationship between their underlying structure and the diffusion kinetics of the HIV/AIDS drug zidovudine using primarily small angle neutron scattering (SANS), rheology and drug release assays.
Methods
SANS [D11 ILL,], oscillatory rheology (loss/storage moduli, critical strain, viscosity, time sweeps), scanning and transmission electron microscopy, circular dichroism, in vitro (phosphate buffered saline) and in vivo (Sprague Dawley rats, subcutaneous injection) drug release for ≥28 days.
Results
SANS demonstrated the gel fiber radius of different peptide hydrogel formulations and peptide gels closely fit model data for the flexible cylinder elliptical model. The presence of entangled gel fibres also suggests a large component of gel stiffness/strength that can be controlled by external conditions e.g., the gelation/formulation process. Drug attached peptide gels were less stiff than gels formed from parent peptide with no drug. SANS showed gels form fibres of narrow radius (~2nm) and large length, a common property of entangled gel fibers.
Conclusion
This research proposes a long-acting injectable drug delivery strategy using peptide-based hydrogels as a water-based formulation and SANS study provide the detail of the hydrogels’ networks information that could potentially tailor properties towards sustained drug delivery.
Eradicating HIV/AIDS by 2030 is a central goal of the World Health Organisation. However, patient compliance with most approved HIV/AIDS treatments is low due to the complexity of drug dosing. The development of a simple, long-term formulation can be an effective way to overcome this challenge. Our formulation is an enzyme-responsive self-assembling low molecular weight D or L-peptide hydrogelator, namely phosphorylated (naphthalene-2-ly)-acetyl-diphenylalanine-lysine-tyrosine-OH (NapFFKY[p]-OH), to which zidovudine is conjugated covalently via an ester linkage. This forms a powder that can be readily dissolved in aqueous buffer to create an injectable solution.
Aims/Objectives
To understand the macroscopic properties of gels and the relationship between their underlying structure and the diffusion kinetics of the HIV/AIDS drug zidovudine using primarily small angle neutron scattering (SANS), rheology and drug release assays.
Methods
SANS [D11 ILL,], oscillatory rheology (loss/storage moduli, critical strain, viscosity, time sweeps), scanning and transmission electron microscopy, circular dichroism, in vitro (phosphate buffered saline) and in vivo (Sprague Dawley rats, subcutaneous injection) drug release for ≥28 days.
Results
SANS demonstrated the gel fiber radius of different peptide hydrogel formulations and peptide gels closely fit model data for the flexible cylinder elliptical model. The presence of entangled gel fibres also suggests a large component of gel stiffness/strength that can be controlled by external conditions e.g., the gelation/formulation process. Drug attached peptide gels were less stiff than gels formed from parent peptide with no drug. SANS showed gels form fibres of narrow radius (~2nm) and large length, a common property of entangled gel fibers.
Conclusion
This research proposes a long-acting injectable drug delivery strategy using peptide-based hydrogels as a water-based formulation and SANS study provide the detail of the hydrogels’ networks information that could potentially tailor properties towards sustained drug delivery.
| Original language | English |
|---|---|
| Publication status | Published - 09 Jan 2023 |
| Event | 17th Annual Meeting of the RSC Biomaterials Chemistry Interest Group - Sheffield Hallam University, Sheffield, United Kingdom Duration: 09 Jan 2023 → 11 Jan 2023 |
Conference
| Conference | 17th Annual Meeting of the RSC Biomaterials Chemistry Interest Group |
|---|---|
| Country/Territory | United Kingdom |
| City | Sheffield |
| Period | 09/01/2023 → 11/01/2023 |
Keywords
- Small Angle Neutron Scattering (SANS))
- Hydrogel
- HIV/AIDS
- Long acting drug delivery systems
- Peptide
Access to Document
- Using Small Angle Neutron Scattering (SANS) to unravel the microscopic properties of long-acting peptide hydrogel drug delivery implants
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