Exploiting the potential of in situ forming liquid crystals : development and in vitro performance of long-acting depots for peptide drug thymosin alpha 1 subcutaneous administration

Vitek, Mercedes (author), Zvonar Pobirk, Alenka (author), Roškar, Robert (author), Gosenca Matjaž, Mirjam (author)

The fast-growing filed of long-acting depots for subcutaneous (SC) administration holds significant potential to enhance patient adherence to treatment regimens, particularly in the context of chronic diseases. Among them, injectable in situ forming lyotropic liquid crystals (LCCs) consisting of hexagonal mesophases represent an attractive platform due to their remarkable highly ordered microstructure enabling the sustained drug release. These systems are especially relevant for peptide drugs, as their use is limited by their short plasma half-life and inherent poor stability. In this study, we thus aimed to exploit the potential of a liquid crystalline platform for the sustained release of peptide drug thymosin alpha 1 (Tα1), characterized by a short plasma half-life and with that associated twice-weekly SC administration regimen. We initially selected specified ingredients, with ethanol serving to reduce viscosity and stabilize the peptide drug Tα1, lecithin contributing to LCCs formation and stabilization, and glycerol monooleate or glycerol monolinoleate representing the hexagonal LCCs forming matrix material. The selected studied nonaqueous precursor formulations were characterized by suitable rheological properties for SC injection. A convenient and rapid in situ phase transition of precursor formulations to hexagonal LCCs, triggered by water absorption, was successfully accomplished in vitro. Notably, in situ formed LCCs demonstrated sustained release kinetics of the peptide drug Tα1 for up to 2 weeks of in vitro release testing, offering minimized dosing frequency and thus promoting patient adherence. In summary, the newly developed in situ forming liquid crystalline systems represent prospective injectable long-acting depots for SC administration of the peptide drug Tα1.The fast-growing filed of long-acting depots for subcutaneous (SC) administration holds significant potential to enhance patient adherence to treatment regimens, particularly in the context of chronic diseases. Among them, injectable in situ forming lyotropic liquid crystals (LCCs) consisting of hexagonal mesophases represent an attractive platform due to their remarkable highly ordered microstructure enabling the sustained drug release. These systems are especially relevant for peptide drugs, as their use is limited by their short plasma half-life and inherent poor stability. In this study, we thus aimed to exploit the potential of a liquid crystalline platform for the sustained release of peptide drug thymosin alpha 1 (Tα1), characterized by a short plasma half-life and with that associated twice-weekly SC administration regimen. We initially selected specified ingredients, with ethanol serving to reduce viscosity and stabilize the peptide drug Tα1, lecithin contributing to LCCs formation and stabilization, and glycerol monooleate or glycerol monolinoleate representing the hexagonal LCCs forming matrix material. The selected studied nonaqueous precursor formulations were characterized by suitable rheological properties for SC injection. A convenient and rapid in situ phase transition of precursor formulations to hexagonal LCCs, triggered by water absorption, was successfully accomplished in vitro. Notably, in situ formed LCCs demonstrated sustained release kinetics of the peptide drug Tα1 for up to 2 weeks of in vitro release testing, offering minimized dosing frequency and thus promoting patient adherence. In summary, the newly developed in situ forming liquid crystalline systems represent prospective injectable long-acting depots for SC administration of the peptide drug Tα1.

• Language: English
• Keywords: glycerol monooleate, glycerol monolinoleate, hexagonal mesophase, subcutaneous injection, microstructure, UHPLC analysis, sustained release, patient adherence
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication version: Version of Record
• Year: 2025
• Number of pages: 18 str.
• Numbering: Vol. 32, iss. 1, [article no.] 2460708
• PID: 20.500.12556/RUL-167795
• UDC: 615:678.027.74-056.24
• ISSN on article: 1521-0464
• DOI: 10.1080/10717544.2025.2460708
• COBISS.SI-ID: 228649219
• Publication date in RUL: 12.03.2025

Record is a part of a journal

• Title: Drug delivery
• Publisher: Taylor & Francis
• ISSN: 1521-0464
• COBISS.SI-ID: 521520409

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: glicerol monooleat, glicerol monolinoleat, heksagonalna mezofazna mikrostruktura, subkutana injekcija, UHPLC analiza, dolgotrajno sproščanje, privrženost bolnika, zdravila, injekcijsko brizganje

Projects

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: P1-0189
• Name: Farmacevtska tehnologija: od dostavnih sistemov učinkovin do terapijskih izidov zdravil pri otrocih in starostnikih

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: L1-3160
• Name: Razvoj visokokoncentriranih proteinskih formulacij in vrednotenje kinetike absorpcije po subkutani aplikaciji