DOI: 10.17034/42d78511-6025-425d-8086-2650acfbe5d7
title: Dataset for "Impact of counterion and salt form on the properties of long-acting injectable peptide hydrogels for drug delivery"

description: Dataset for paper entitled "Impact of counterion and salt form on the properties of long-acting injectable peptide hydrogels for drug delivery".

Abstract for paper: Modifying the salt form of active pharmaceutical ingredients is a common method to enhance their physicochemical and biological properties, whilst improving their abiliy to be formulated into medicines that can be effectively delivered to patients. Salts and counterions are especially relevant to peptide therapies given that the majority of low molecular weight peptides synthesised by solid-phase protocols form a trifluoroacetate (TFA) salt due to the use of trifluoroacetic acid in resin cleaving and follow-on purification methods. TFA salts are not viewed as favourably by medicine regulators and can be defined as a new chemical entity entirely due to their different biological and physicochemical properties. Despite some exceptions, the vast majority of therapeutic peptides are marketed as hydrochloride (HCl) or acetate salts, even though most early research and development is centred on TFA salts. The aim of study was to compare the impact of salt form (TFA vs. HCl) on the biostability, cell cytotoxicity, drug release and rheological properties of a Napffky(p)G-OH peptide hydrogel platform that demonstrates promise as a long-acting drug delivery system. This study demonstrated no significant difference between the salt forms for properties important to its intended use. This paper also raises important points for discussion relating to the environmental and regulatory status of peptide salts and their use as pharmaceuticals. 

Dataset information: 
There is an urgent need for new long-acting formulations to improve patient access and adherence to medicines. Several marketed long-acting injectable nanosuspensions comprising water-insoluble drugs are utilised for treatment of schizophrenia and for pre-exposure prophylaxis (PrEP) against HIV infection. In situ forming peptide and peptide-like hydrogels hold significant promise to overcome some of the disadvantages associated with existing nanosuspension injections including: the need for water-insoluble drugs; challenges encountered incorporating multiple drugs within one injectable product; the formation of amorphous drug during milling; and difficulties relating to large-scale manufacture. The majority of peptides synthesised by solid-phase protocols result in a trifluoroacetate salt due to the use of trifluoroacetic acid in resin cleaving and purification steps. Trifluoroacetate salts are not viewed favourably by Medicine regulators e.g. MHRA, FDA, EMA, and are commonly defined as a new chemical entity entirely due to their impact on the biological and physicochemical properties of peptides. Therefore the vast majority of therapeutic peptides are marketed as hydrochloride (HCl) or acetate salts. Despite this, the vast majority of early research and development is centred on TFA salts. The aim of study was to compare the impact of HCl salt conversion on the biostability, cell cytotoxicity, drug release and rheological properties of our Napffky(p)G-OH peptide hydrogel platform.

All files provide a comparison of data for (naphthalene-2-ly)-acetyl-D-phenylalanine-D-phenylalanine-D-lysine-phosphorylated D-tyrosine-glycine-OH (Napffky(p)G-OH) in both HCl and TFA salt forms.

Studies were conducted and data generated using the equipment and methods outlined within the readme file (Combined Institutional readme file for Impact of counterion and salt form on the properties dataset in Pure) at the School of Pharmacy, Queen's University Belfast between 20/07/20 and 30/09/24.

This data is likely to be of relevance to researchers working within the pharmaceutical and drug delivery field. Especially those with an interest in the impact of different salt forms of drugs on their properties and those involved in the development of peptide medicines and peptide-based materials. 

More specific details in relation to the source and definition of data is outlined within the readme file entitled "Combined Institutional readme file for Impact of counterion and salt form on the properties dataset in Pure." Only one readme file is used to define this dataset.

This dataset contains:
Biostability.csv 
This file relates to the biostability of (naphthalene-2-ly)-acetyl-D-phenylalanine-D-phenylalanine-D-lysine-phosphorylated D-tyrosine-glycine-OH (Napffky(p)G-OH) in both HCl and TFA salt forms against the protease enzyme proteinase K for 28 day time period.
 
Frequency sweeps rheology.csv
Strain sweeps rheology.csv
Time sweeps rheology.csv

These files relates to the oscillatory rheological properties of (naphthalene-2-ly)-acetyl-D-phenylalanine-D-phenylalanine-D-lysine-phosphorylated D-tyrosine-glycine-OH (Napffky(p)G-OH) in both HCl and TFA salt forms. Frequency sweeps provide an indication of gel formation via storage modulus G' and loss modulus G'' measurements. Strain sweeps provide an indication of gel strength and time sweeps demonstrate time for gelation in response to phosphatase enzyme.

MTS 6 hours.csv
MTS 24 hours.csv
MTS 48 hours.csv
MTS 72 hours.csv

MTS files relate to cell metabolic activity of NCTC 929 cells after stated exposure time (6, 24, 48 and 72 hours) to (naphthalene-2-ly)-acetyl-D-phenylalanine-D-phenylalanine-D-lysine-phosphorylated D-tyrosine-glycine-OH (Napffky(p)G-OH) in both HCl and TFA salt forms.

Cabotegravir release.csv
This file relates to the drug (cabotegravir) release properties of each peptide gel of (naphthalene-2-ly)-acetyl-D-phenylalanine-D-phenylalanine-D-lysine-phosphorylated D-tyrosine-glycine-OH (Napffky(p)G-OH) in both HCl and TFA salt forms over 28 days.