Alice McCloskey

Dr. Alice McCloskey

orcid

Research Focus & Metrics

Academic Career Length

13Years (2014-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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7 August 2014 in Biomacromolecules
Verified
Journal Article
Closed access
GLGarry Laverty
Garry Laverty
AMAlice McCloskey
Alice McCloskey
BGBrendan F. Gilmore
Brendan F. Gilmore
DJDavid S. Jones
David S. Jones
JZJie Zhou
Jie Zhou
BXBing Xu
Bing Xu

5 December 2016 in Current Medicinal Chemistry
Verified
Journal Article
Closed access
JRJohn Rafferty
John Rafferty
HNHema Nagaraj
Hema Nagaraj
AMAlice McCloskey
Alice McCloskey
RHRawan Huwaitat
Rawan Huwaitat
SPSimon Porter
Simon Porter
GLGarry Laverty
Garry Laverty
Peptides are receiving increasing interest as clinical therapeutics. These highly tunable molecules can be tailored to achieve desirable biocompatibility and biodegradability with simultaneously selective and potent therapeutic effects. Despite challenges regarding up-scaling and licensing of peptide products, their vast clinical potential is reflected in the 60 plus peptide-based therapeutics already on the market, and the further 500 derivatives currently in developmental stages. Peptides are proving effective for a multitude of disease states including: type 2 diabetes (controlled using the licensed glucagon-like peptide-1 receptor liraglutide); irritable bowel syndrome managed with linaclotide (currently at approval stages); acromegaly (treated with octapeptide somostatin analogues lanreotide and octreotide); selective or broad spectrum microbicidal agents such as the Gram-positive selective PTP-7 and antifungal heliomicin; anticancer agents including goserelin used as either adjuvant or monotherapy for prostate and breast cancer, and the first marketed peptide derived vaccine against prostate cancer, sipuleucel-T. Research is also focusing on improving the biostability of peptides. This is achieved through a number of mechanisms ranging from replacement of naturally occurring L-amino acid enantiomers with D-amino acid forms, lipidation, peptidomimetics, N-methylation, cyclization and exploitation of carrier systems. The development of self-assembling peptides are paving the way for sustained release peptide formulations and already two such licensed examples exist, lanreotide and octreotide. The versatility and tunability of peptide-based products is resulting in increased translation of peptide therapies, however significant challenges remain with regard to their wider implementation. This review highlights some of the notable peptide therapeutics discovered to date and the difficulties encountered by the pharmaceutical industry in translating these molecules to the clinical setting for patient benefit, providing some possible solutions to the most challenging barriers.

9 January 2017 in Journal of Peptide Science
Verified
Journal Article
Closed access
PDF file
AMAlice McCloskey
Alice McCloskey
EDEmily R. Draper
Emily R. Draper
BGBrendan F. Gilmore
Brendan F. Gilmore
GLGarry Laverty
Garry Laverty

3 October 2014 in Pathogens
Verified
Journal Article
Open access
PDF file
AMAlice McCloskey
Alice McCloskey
Brendan GilmoreBrendan Gilmore
Brendan Gilmore
GLGarry Laverty
Garry Laverty
Biomaterial-related infections are a persistent burden on patient health, recovery, mortality and healthcare budgets. Self-assembled antimicrobial peptides have evolved from the area of antimicrobial peptides. Peptides serve as important weapons in nature, and increasingly medicine, for combating microbial infection and biofilms. Self-assembled peptides harness a “bottom-up” approach, whereby the primary peptide sequence may be modified with natural and unnatural amino acids to produce an inherently antimicrobial hydrogel. Gelation may be tailored to occur in the presence of physiological and infective indicators (e.g. pH, enzymes) and therefore allow local, targeted antimicrobial therapy at the site of infection. Peptides demonstrate inherent biocompatibility, antimicrobial activity, biodegradability and numerous functional groups. They are therefore prime candidates for the production of polymeric molecules that have the potential to be conjugated to biomaterials with precision. Non-native chemistries and functional groups are easily incorporated into the peptide backbone allowing peptide hydrogels to be tailored to specific functional requirements. This article reviews an area of increasing interest, namely self-assembled peptides and their potential therapeutic applications as innovative hydrogels and biomaterials in the prevention of biofilm-related infection.

5 December 2016 in RSC Advances
Verified
Journal Article
Closed access
PDF file
AMAlice McCloskey
Alice McCloskey
SGS. M. Gilmore
S. M. Gilmore
JZJ. Zhou
J. Zhou
Emily DraperEmily Draper
Emily Draper
SPS. Porter
S. Porter
GLGarry Laverty
Garry Laverty
Peptide-based materials are receiving significant attention for use within biomedicine due to their high chemical and functional versatility enabling tailoring of their structure to replicate the properties of host tissue and the extracellular matrix. This paper studies the design, synthesis and characterization of NSAID-peptide conjugates. Attachment of NSAIDs to a diphenylalanine–dilysine (FFKK-OH) peptide sequence generates supramolecular hydrogel forming molecules with antimicrobial and anti-inflammatory properties. NSAID-peptides demonstrate broad-spectrum antimicrobial activity against both Gram-positive and Gram-negative bacteria implicated in a variety of antimicrobial resistant nosocomial infections including Staphylococcus aureus and Pseudomonas aeruginosa. Naproxen-peptides show particular promise, forming biocompatible nanofibrous viscoelastic hydrogel nanosponges composed of β-sheet secondary structures at low concentrations (0.4% w/v). Conjugation of the peptide motif FFKK-OH to naproxen increases selectivity for COX-2 enzyme, implicated in chronic wound scar-tissue formation. Our findings suggest that ultrashort NSAID-peptides have potential use as multifunctional materials for a range of biomedical applications. This includes as topical agents for treatment of chronic wounds, where a profile of persistent inflammation, pain and the presence of infection has been proven to be detrimental to successful wound repair. This work may also serve as a template for the design of future medical device coatings with tailored antimicrobial and anti-inflammatory properties.

2 August 2022 in British Journal of Clinical Pharmacology
Verified
Journal Article
Open access
AMAlice McCloskey
Alice McCloskey
Peter PensonPeter Penson
Peter Penson
YTYincent Tse
Yincent Tse
MAMajadah A. Abdelhafiz
Majadah A. Abdelhafiz
SAShah N. Ahmed
Shah N. Ahmed
ELEmma J. Lim
Emma J. Lim
Solid oral dosage forms (SODFs) (often called pills by patients) are the default formulation to treat medical ailments. Beneficial therapeutic outcomes rely on patients taking them as directed. Up to 40% of the population experience difficulties swallowing SODFs, resulting in reduced adherence and impaired therapeutic efficacy. Often associated with children, this also presents in adults with dysphagia, and without any organic dysphagia (non‐physiological‐related or functional dysphagia). This review aims to identify and appraise current interventions used to screen for and overcome pill aversion in adults with functional dysphagia. A comprehensive search of the literature was conducted. Articles reporting pill aversion in adults aged ≥18 years with no underlying cause, history of, or existing dysphagia were included. Study quality was determined using the STROBE tool for observational studies. A narrative synthesis of the findings was prepared. We identified 18 relevant cohort studies, which demonstrate that pill aversion is a global problem. Perceived ease of and/or SODF swallowability appears to be influenced by female gender, younger age, co‐morbidities (e.g., depression), and physical SODF properties. Patients often modify their medicines rather than raise this issue with their healthcare team. Screening for pill aversion is haphazard but controlled postural adjustments, coating SODFs and behavioural interventions appear to be successful solutions. SODF swallowing difficulties are a barrier to effective medication use. Healthcare professionals must recognise that pill aversion is a problem requiring identification through effective screening and resolution by training interventions, appropriate formulation selection or specialist referral.