Linear aliphatic polyesters, such as poly-l-lactide (PLLA), have garnered considerable attention as nanocarriers in drug delivery due to their biocompatibility and biodegradability. The main disadvantages of these polymers are the lack of functional groups and high crystallinity degree that may negatively affect drug loading and polymer degradation rate [1].
To overcome these drawbacks, two strategies were investigated, involving the blending of PLLA with polyglycerol adipate (PGA), an amorphous polyester endowed with free OH groups, or the synthesis of branched PLLA (3 or 4 arms) by using polyols, glycerol or diglycerol, as initiators. Usnic acid (UA), a lichen metabolite with well know antimicrobial and anticancer activity, was investigated for encapsulation as model hydrophobic drug [2].
Blending PLLA-PGA at 50/50 weight ratio allowed us to decrease nanoparticles’ size (from 140 nm of pure PLLA to 110 nm), increase nanoparticle degradation and improve UA loading as well as the ability to decrease UA cytotoxicity towards human hepatocytes (HepG2 cells) [3].
Branched PLLA with molecular weight (MW) ranging from 4100 to 20000 g mol−1 were obtained by varying L-lactide (L-LA)/OH molar ratios (8, 16 and 24). SAXS evidenced the scattering of a single polymer chain for low molecular weight polymers and the formation of aggregates with planar geometry, possibly vesicles for polymers with 6-12 KDa MW. All branched polymers were amorphous, except for the polymer with the longest branched, and able to self-assemble in water giving 200 nm-in size nanoaggregates. An efficient UA and reduced toxicity were obtained in comparison to linear PLLA.
1. Washington, K.E.; Kularatne, R.N.; Karmegam, V.; Biewer, M.C.; Stefan, M.C. Recent Advances in Aliphatic Polyesters for Drug Delivery Applications. WIREs Nanomedicine Nanobiotechnology 2017, 9 (4), e1446, DOI:10.1002/wnan.1446.
2. Brugnoli, B.; Mariano, A.; Simonis, B.; Bombelli, C.; Sennato, S.; Piozzi, A.; Taresco, V.; Chauhan, V.M.; Howdle, S.M.; Scotto d’Abusco, A.; et al. Self-Assembled Chitosan-Sodium Usnate Drug Delivery Nanosystems: Synthesis, Characterization, Stability Studies, in Vitro Cytotoxicity and in Vivo Biocompatibility against 143 B Cells. Carbohydr. Polym. Technol. Appl. 2023, 6, 100373, DOI:10.1016/j.carpta.2023.100373.
3. Brugnoli, B.; Perna, G.; Alfano, S.; Piozzi, A.; Galantini, L.; Axioti, E.; Taresco, V.; Mariano, A.; Scotto d’Abusco, A.; Vecchio Ciprioti, S.; et al. Nanostructured Poly-l-Lactide and Polyglycerol Adipate Carriers for the Encapsulation of Usnic Acid: A Promising Approach for Hepatoprotection. Polymers 2024, 16 (3), 427, DOI:10.3390/polym16030427.