Poly(<span style="font-variant: small-caps">l</span>-Lactic Acid)-co-poly(Butylene Adipate) New Block Copolymers for the Preparation of Drug-Loaded Long Acting Injectable Microparticles
Vasiliki Karava,
Aggeliki Siamidi,
Marilena Vlachou,
Evi Christodoulou,
Nikolaos D. Bikiaris,
Alexandra Zamboulis,
Margaritis Kostoglou,
Eleni Gounari,
Panagiotis Barmpalexis
Affiliations
Vasiliki Karava
Department of Pharmacy, Section of Pharmaceutical Technology, Zografou Campus, National and Kapodistrian University of Athens, 15784 Athens, Greece
Aggeliki Siamidi
Department of Pharmacy, Section of Pharmaceutical Technology, Zografou Campus, National and Kapodistrian University of Athens, 15784 Athens, Greece
Marilena Vlachou
Department of Pharmacy, Section of Pharmaceutical Technology, Zografou Campus, National and Kapodistrian University of Athens, 15784 Athens, Greece
Evi Christodoulou
Department of Chemistry, Laboratory of Polymer Chemistry and Technology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
Nikolaos D. Bikiaris
Department of Chemistry, Laboratory of Polymer Chemistry and Technology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
Alexandra Zamboulis
Department of Chemistry, Laboratory of Polymer Chemistry and Technology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
Margaritis Kostoglou
Laboratory of Chemical and Environmental Technology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
The present study evaluates the use of newly synthesized poly(l-lactic acid)-co-poly(butylene adipate) (PLA/PBAd) block copolymers as microcarriers for the preparation of aripiprazole (ARI)-loaded long acting injectable (LAI) formulations. The effect of various PLA to PBAd ratios (95/5, 90/10, 75/25 and 50/50 w/w) on the enzymatic hydrolysis of the copolymers showed increasing erosion rates by increasing the PBAd content, while cytotoxicity studies revealed non-toxicity for all prepared biomaterials. SEM images showed the formation of well-shaped, spherical MPs with a smooth exterior surface and no particle’s agglomeration, while DSC and pXRD data revealed that the presence of PBAd in the copolymers favors the amorphization of ARI. FTIR spectroscopy showed the formation of new ester bonds between the PLA and PBAd parts, while analysis of the MP formulations showed no molecular drug–polyester matrix interactions. In vitro dissolution studies suggested a highly tunable biphasic extended release, for up to 30 days, indicating the potential of the synthesized copolymers to act as promising LAI formulations, which will maintain a continuous therapeutic level for an extended time period. Lastly, several empirical and mechanistic models were also tested, with respect to their ability to fit the experimental release data.
