Stability Test of PACAP in Eye Drops

Abstract

PACAP is a neuropeptide with widespread distribution and diverse biological functions. It has strong cytoprotective effects mediated mainly through specific PAC1 receptors. Experimental data show protective effects of PACAP in the retina and cornea in several pathological conditions. Although intravitreal injections are a common practice in some ocular diseases, delivery of therapeutic agents in the form of eye drops would be more convenient and would lead to fewer side effects. We have previously shown that PACAP, in the form of eye drops, is able to pass through the ocular barriers and can exert retinoprotective effects. As eye drops represent a promising form of administration of PACAP in ocular diseases, it is important to investigate the stability of PACAP in solutions used in eye drops. In this study, the stability of PACAP1-27 and PACAP1-38 in eye drops was measured in four common media and a commercially available artificial tear solution at both room temperature and +4°C. Mass spectrometry results show that the highest stability was gained with PACAP1-38 in water and 0.9% saline solution at +4°C, representing 80-90% drug persistence after 2 weeks. PACAP1-38 in the artificial tear showed very fast degradation at room temperature, but was stable at +4°C. In summary, PACAP1-38 has higher stability than PACAP1-27, with highest stability at +4°C in water solution, but both peptides in each medium can be stored for relatively longer periods without significant degradation. These data can provide reference for future therapeutic use of PACAP in eye drops.

Relevance of Peptide Homeostasis in Metabolic Retinal Degenerative Disorders: Curative Potential in Genetically Modified Mice

“…In addition, a number of other methods are being considered, including biodegradable implants ( Mandal et al, 2018 ). It is important to note that NPs used for experimental or therapeutic purposes might also need to be stabilized against degradation and enzymatic breakdown ( Mandal et al, 2018 ; Kovacs et al, 2021 ), meaning that choosing the method of delivery is crucial for any curative research.…”

PACAP and NAP: Effect of Two Functionally Related Peptides in Diabetic Retinopathy

“…This neuropeptide was first isolated from ovine hypothalamus by Miyata and coworkers in 1989. PACAP and its related receptors are expressed in the central nervous system (CNS) and in most peripheral organs (Ghatei et al 1993;Arimura and Shioda 1995;Vaudry 2009;Moody et al 2020;Girard et al 2020;Toth et al 2020). This peptide exists in two isoforms: PACAP38, which includes 38 aminoacids, and PACAP27, which is PACAP-38 truncated in C-terminal form and includes 27 aminoacids.…”

“…PACAP is a pleiotropic peptide, as it is involved in a wide array of physiological processes such as neuromodulation of immune response, neuroprotection, and stimulation of cell proliferation. It also plays a protective effect in several pathologies affecting the CNS and eye, including retinopathies (Canonico et al 1996;Arimura et al, 1998;Vaudry et al 2003;2009;Giunta et al 2010;Nackamachi et al 2011Nackamachi et al , 2012Nackamachi et al , 2016Atlasz et al 2010a and2010b;Varga et al 2011;Scuderi et al 2013;Castorina et al 2014;Maugeri et al 2018;2019a;Kovacs et al 2020;Martínez-Rojas et al 2020;Józsa et al 2001).…”

Protective Effects of PACAP in a Rat Model of Diabetic Neuropathy

“…One of the established effects of the neuropeptide is its neurotrophic/neuroprotective action [17][18][19][20][21][22]. This has been proven in numerous neuronal insults and models of neurodegenerative diseases, such as spinal atrophy [23], amyotrophic lateral sclerosis [24], Alzheimer's disease [25][26][27], stroke [28][29][30], Parkinson's disease [20,[31][32][33], Huntington chorea [34], and several types of retinal injuries [21,[35][36][37].…”