L-Arginine/L-Histidine/L-Isoleucine/L-Leucine/L-Lysine Hydrochloride/L-Methionine/L-Phenylalanine/L-Threonine/N-Acetyl-L-Tryptophan/L-Valin/Glycine/Glucose

Curcumin (CUR) has potent anticancer activities, and its bioformulations, including biodegradable polymers, are increasingly able to improve CUR's solubility, stability, and delivery to cancer cells. In this study, copolymers comprising poly (L-lactide)-poly (ethylene glycol)-poly (L-lactide) (PLA-PEG-PLA) and poly (ethylene glycol)-poly (L-lactide)-poly (ethylene glycol) (PEG-PLA-PEG) were designed and synthesized to assess and compare their CUR-delivery capacity and inhibitory potency on MCF-7 breast cancer cells. Molecular dynamics simulations and free energy analysis indicated that PLA-PEG-PLA has a higher propensity to interact with the cell membrane and more negative free energy, suggesting it is the better carrier for cell membrane penetration. To characterize the copolymer synthesis, Fourier transform-infrared (FT-IR) and proton nuclear magnetic resonance (¹H-NMR) were employed, copolymer size was measured using dynamic light scattering (DLS), and their surface charge was determined by zeta potential analysis. Characterization indicated that the ring-opening polymerization (ROP) reaction was optimal for synthesizing high-quality polymers. Microspheres comprising the copolymers were then synthesized successfully. Of the two formulations, PLA-PEG-PLA experimentally exhibited better results, with an initial burst release of 17.5%, followed by a slow, constant release of the encapsulated drug up to 80%. PLA-PEG-PLA-CUR showed a significant increase in cell death in MCF-7 cancer cells (IC₅₀ = 23.01 ± 0.85 µM) based on the MTT assay. These data were consistent with gene expression studies of Bax, Bcl2, and hTERT, which showed that PLA-PEG-PLA-CUR induced apoptosis more efficiently in these cells. Through the integration of nano-informatics and in vitro approaches, our study determined that PLA-PEG-PLA-CUR is an optimal system for delivering curcumin to inhibit cancer cells.

Recently, great attention has been paid to developing new drug delivery systems to manage the rate, time, and site of drug release. We aimed to design a novel drug delivery system to support targeted and gradual delivery of levothyroxine sodium.

The triblock copolymers of PLA-PEG-PLA and PLGA-PEG-PLGA were constructed using the ring-opening copolymerization method and then purified and characterized by 1H-NMR, DSC, and GPC techniques. The phase transition temperature of the polymers was determined, and levothyroxine sodium stability was investigated in a phosphate-based buffer (pH 7.4). In vitro drug release into the PBS was measured at different concentrations of the triblocks for one month.

The results of NMR and GPC showed successful fabrication of the copolymers with low molecular weight dispersion and T_g points of -8.19 ^°C and -5.19 ^°C for PLA-PEG-PLA and PLGA-PEG-PLGA, respectively. Stability tests showed that during one month, most of the triblocks' masses degraded at 37 ^°C while levothyroxine sodium remained stable. Initial burst release of the drug in both copolymers is inversely correlated with the concentration of the polymer. Evaluation of drug release for 35 days showed that PLA-PEG-PLA had a slower drug release rate than PLGA-PEG-PLGA.

Considering the low initial burst release, as well as continuous and long-term release kinetics of PLA-PEG-PLA and PLGA-PEG-PLGA copolymers, they can be used to gradually deliver levothyroxine sodium, obviating the need for frequent administrations and concerns over drug-food interactions.