First Systematic Review with Meta-Analysis on the Effect of Cyclodextrins on the Pharmacological Activity of Antihypertensive Drugs

Background/Objectives: Despite the availability of numerous antihypertensive agents, achieving effective and sustained blood pressure control remains a challenge. Treatment-resistant hypertension, dose-limiting adverse effects, and poor oral bioavailability are among the major factors limiting the efficacy of conventional antihypertensive therapy. Cyclodextrins (CDs) are widely investigated as potential drug delivery systems for various therapeutic classes owing to their favorable safety profile, biocompatibility, chemical inertness, and structural diversity. Through the formation of inclusion complexes, CDs may improve the aqueous solubility, stability, and bioavailability of poorly water-soluble drugs, thereby enhancing their performance. We aimed to systematically evaluate the potential of cyclodextrins as drug delivery systems for enhancing the pharmaceutical properties of antihypertensive agents, providing the first systematic review and meta-analysis in this field. Methods: We applied the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA) to perform our research. Results: The synthesized literature reveals that most CD–antihypertensive complexes exhibit a 1:1 molecular stoichiometry, though 1:2 and 1:3 guest-to-host ratios also occur. This review establishes that CD complexation improves drug release kinetics, enhances stability, and increases aqueous solubility of the antihypertensive agents. In vivo studies confirm the low toxicity and robust therapeutic efficacy of these complexes. Finally, a meta-analysis of four quantitative studies corroborates the potency of CDs as effective delivery vehicles of compounds with antihypertensive effects. Conclusions: These findings underscore the potential of CDs in hypertension management and highlight the critical need for more in vivo studies and clinical trials to achieve a comprehensive therapeutic evaluation.