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.

In vitro formulation development and characterization study

“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)...”

Injectable in situ forming lyotropic liquid crystals (LCCs) containing the peptide drug thymosin alpha 1 (Tα1)

“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.”

Eight selected precursor formulations were characterized, with experiments performed in triplicate or quadruplicate depending on the test

“Based on the obtained results, eight precursor formulations were then selected for further characterization.”

In vitro release testing was conducted over a period of 2 weeks

“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.”

The precursor formulations underwent rapid in situ phase transition to hexagonal LCCs upon water absorption, with gelation times ranging from 2.5 to 70.0 seconds.

“A convenient and rapid in situ phase transition of precursor formulations to hexagonal LCCs, triggered by water absorption, was successfully accomplished in vitro.”

The in situ formed LCCs demonstrated sustained release of Tα1, with total drug release after 2 weeks ranging from 5.5% to 93.4% depending on the formulation composition.

“(E/L)Go80 and (E/L)Gl80 exhibited the greatest total drug release after 2 weeks with 84.2% and 93.4%, respectively.”

Formulations containing only hexagonal mesophases exhibited lower drug release compared to those with coexisting lamellar mesophases, correlating with lower water uptake capacity.

“It is known from the literature that the release of hydrophilic drugs from lamellar LCCs, which are in general more highly hydrated mesophases, is more rapid than from hexagonal LCCs with relatively low water absorption.”

The study was conducted entirely in vitro, and the release medium required the addition of ethanol to maintain peptide stability, which may not fully replicate physiological conditions.

“Considering physiological conditions after SC administration and chemical stability of peptide drug Tα1, PBS (pH = 6.8) containing 5% (m/m) of ethanol was selected as the most appropriate release medium for the test completion in 2 weeks at 37 °C.”