Cyclodextrins (CDs) have revolutionized the pharmaceutical industry with their ability to enhance the stability, solubility, and bioavailability of a wide range of active substances. These cyclic oligosaccharides, with a unique hydrophilic exterior and hydrophobic cavity, form inclusion complexes with poorly soluble drugs, improving their pharmacokinetic profiles and therapeutic efficacy. This review explores the multifaceted roles of cyclodextrins in pharmaceutical formulations, ranging from oral, ophthalmic, parenteral, and topical applications to their emerging use in targeted therapies, gene delivery, and treatment of neurodegenerative, cardiovascular, and infectious diseases. Cyclodextrins not only improve drug solubility and controlled release but also reduce toxicity and side effects, leading to safer and more effective treatments. Recent advancements, such as cyclodextrin-based nanoparticles, offer promising pathways for cancer therapy, chronic disease management, and personalized medicine. As research continues, cyclodextrins remain at the forefront of innovation in drug delivery systems, ensuring better patient outcomes and expanding the possibilities of modern therapeutics.
This review investigates innovative strategies for upcycling agricultural residues into valuable pharmaceutical compounds. The improper disposal of agricultural residues contributes to significant environmental issues, including increased greenhouse gas emissions and ecosystem degradation. Upcycling offers a sustainable solution, transforming these residues into high-value bioproducts (antioxidants, antitumor agents, antidiabetic compounds, anti-inflammatory agents, and antiviral drugs). Nanotechnology and microbial biotechnology have a crucial role in enhancing bioavailability and targeted delivery of bioactive compounds. Advanced techniques like enzymatic hydrolysis, green solvents, microwave processing, pyrolysis, ultrasonic processing, acid and alkaline hydrolysis, ozonolysis, and organosolv processes are explored for their effectiveness in breaking down agricultural waste and extracting valuable compounds. Despite the promising potential, challenges such as variability in residue composition, scalability, and high costs persist. The review emphasizes the need for future research on cost-effective extraction techniques and robust regulatory frameworks to ensure the safety, efficacy, and quality of bioproducts. The upcycling of agricultural residues represents a viable path towards sustainable waste management and production of pharmaceutical compounds, contributing to environmental conservation and public health improvements. This review provides an analysis of the current literature and identifies knowledge gaps, offering recommendations for future studies to optimize the use of agricultural residues in the drug industry.
This study investigated, for the first time, the phenolic acid profile along with the in vitro antioxidant and acetylcholinesterase (AChE) inhibitory activities of leaves and fruits from five Romanian wild-grown Acer spp. (Sapindaceae): A. campestre L., A. monspessulanum L., A. platanoides L., A. pseudoplatanus L., and A. tataricum L. High-performance liquid chromatography coupled with ultraviolet and mass spectrometry (HPLC/UV/MS) was employed to identify and quantify key phenolic acids, including gallic, caffeic, protocatechuic, chlorogenic, and p-coumaric acids. Total phenolic content (TPC) ranged from 61.48 ± 3.76 to 512.8 ± 20.54 µg gallic acid equivalents (GAE)/mL. Antioxidant activities, assessed through 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays, demonstrated the strongest radical scavenging capacities for A. tataricum fruits, with half maximal inhibitory concentration (IC50) values of 10.88 ± 3.39 µg/mL and 10.39 ± 2.86 µg/mL, respectively. The ferric-reducing antioxidant power (FRAP) assay revealed the highest reducing power for A. tataricum fruits (1158 ± 48.98 µmol Fe2+/L) and leaves (1119 ± 164.6 µmol Fe2+/L). AChE inhibition was only found in A. tataricum, with an IC50 of 7.91 ± 7.50 mg/mL for leaves and 15.95 ± 8.52 mg/mL for fruits. These results highlight A. tataricum as a promising source of natural antioxidants and neuroprotective agents.
Palbociclib and abemaciclib are two cyclin-dependent kinases 4 and 6 used for breast cancer treatment. Levels of these medicines present a significant interindividual variability, so monitoring those concentrations might be necessary in therapy. Most of the methods presented so far in the literature use simple protein precipitation of plasma proteins as sample preparation method followed by direct injection of the supernatant into the LC instrument, preceded or not by a simple filtration step. Within that approach, the probability of injecting proteins in the chromatographic system is increased. With the purpose of obtaining a cleaner extract of the drugs, we developed and validated a simple and accurate LC-MS method for determining palbociclib and abemaciclib in human plasma. Solid phase extraction (SPE) using Oasis PRiME HLB® cartridges was used for plasma sample preparation. The method provided clean extracts with a recovery extraction higher than 85% for both compounds. Separation was achieved by high-performance liquid chromatography (HPLC), using a C18 (4.6 × 50 mm) column, with a gradient elution of ammonium acetate/acetic acid-acetonitrile as the mobile phase. Detection was performed by mass spectrometry (MS) in single ion recording (SIR) mode. Intra-day and inter-day precision data for both analytes were 3.8–7.2% and 3.6–7.4%, respectively. Calibration curves were both linear between 2 and 400 ng/mL with a correlation coefficient higher than 0.998. The LC-MS method can be used to quantify the drugs in human plasma in routine analysis. The method proved to be useful in determining real plasma levels in patients involved in cancer therapy. Drug concentrations were determined in a 10 min run-time, including re-equilibration of the column.
Caffeine is a widely consumed psychoactive compound known to influence drug metabolism and efficacy through interactions with key enzymes such as cytochrome P450 3A4 (CYP3A4). This study investigates the molecular impact of caffeine on the binding behavior of imatinib, a first-line BCR-ABL tyrosine kinase inhibitor, using molecular docking simulations. Structural optimization and lipophilicity analyses were conducted using HyperChem, while docking was performed with HEX software (Version 8.0.0) against the CYP3A4 receptor (PDB ID: 1W0E). Two administration scenarios were evaluated: concurrent caffeine–imatinib complex formation and sequential administration with caffeine pre-bound to CYP3A4. The caffeine–imatinib complex exhibited a predicted increase in lipophilicity (logP = 3.09) compared to imatinib alone (logP = −1.29), which may indicate the potential for enhanced membrane permeability and tissue distribution. Docking simulations revealed stronger binding affinity of the complex to CYP3A4 (−350.53 kcal/mol) compared to individual compounds, and improved imatinib binding when CYP3A4 was pre-complexed with caffeine (−294.14 kcal/mol vs. −288.19 kcal/mol). Frontier molecular orbital analysis indicated increased reactivity of the complex (ΔE = 7.74 eV), supporting the hypothesis of altered pharmacodynamic behavior. These findings suggest that caffeine may modulate imatinib’s metabolic profile and therapeutic efficacy by enhancing receptor binding and altering drug distribution. The study underscores the importance of evaluating dietary components during drug development and therapeutic planning, particularly for agents metabolized by CYP3A4.
The current strategy for treating osteomyelitis includes surgical procedures for complete debridement of the formed biofilm and necrotic tissues, systemic and oral antibiotic therapy, and the clinical use of cements and three-dimensional scaffolds as bone defect fillers and delivery systems for therapeutic agents. The aim of our research was to formulate a low-cost hybrid nanoparticulate biomaterial using poly(lactic-co-glycolic acid) (PLGA), in which we incorporated the therapeutic agent (ciprofloxacin), and to deposit this material on titanium plates using the matrix-assisted pulsed laser evaporation (MAPLE) technique. The deposited material demonstrated antibacterial properties, with all analyzed samples inhibiting the growth of tested bacterial strains, confirming the release of active substances from the investigated biocomposite. The poly(lactic-co-glycolic acid)-ciprofloxacin (PLGA-CIP) nanoparticle scaffolds displayed a prolonged local sustained release profile over a period of 45 days, which shows great promise in bone infections. Furthermore, the burst release ensures a highly efficient concentration, followed by a constant sustained release which allows the drug to remain in the implant-adjacent area for an extended time period.