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Lorina CIOBANU, Ion PREGUZA, Vasile GALEARSCHI. Polymeric Nanovectors for Targeted Delivery of Matrix Metalloproteinase Inhibitors to the Vascular Wall in Cerebral Aneurysms; Proceedings of NanoBioMat 2026(1); 171-198
POLYMERIC NANOVECTORS FOR TARGETED DELIVERY OF MATRIX METALLOPROTEINASE INHIBITORS TO THE VASCULAR WALL IN CEREBRAL ANEURYSMS
Lorina CIOBANU 1,*, Ion PREGUZA 1, Vasile GALEARSCHI 1
1 Department of Neurosurgery, Nicolae Testemitanu State University of Medicine and Pharmacy,
Chișinău, Republic of Moldova
*Correspondence to: lorinaciobanu01@gmail.com
ABSTRACT
Introduction: Cerebral aneurysms affect approximately 2-5% of the general population and represent a leading cause of non-traumatic subarachnoid hemorrhage, with mortality rates reaching up to 60% following rupture. Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, drive the proteolytic degradation of the extracellular matrix (ECM) in the aneurysmal wall, constituting a validated molecular target for pharmacological intervention [1, 2, 3].
Aim of the study: To examine the molecular role of MMP-2 and MMP-9 in intracranial aneurysm (IA) pathogenesis and evaluate the current evidence for MMP inhibitors (MMPi) including batimastat (BB-94), marimastat, and doxycycline, and critically appraise the published preclinical data on PLGA-based polymeric nanovectors as targeted delivery platforms for MMPi to the vascular wall.
Materials and methods: A structured search of PubMed/MEDLINE, ScienceDirect, Google Scholar, and the Cochrane Library was performed using key terms including 'intracranial aneurysm', 'MMP inhibitor', 'PLGA nanoparticles', 'targeted drug delivery', and 'vascular wall remodeling'. Articles published between 2000 and 2025 were considered; original research articles, systematic reviews, and meta-analyses with quantitative outcomes were included. Case reports, non-English publications, and studies on non-vascular MMP applications were excluded.
Results: MMP-2 and MMP-9 are consistently overexpressed in human aneurysmal tissue and are causally linked to ECM destruction and wall weakening. Systemic MMP inhibitors show preclinical efficacy but are constrained by poor bioavailability and dose-limiting toxicity. Anti-elastin antibody-functionalized PLA nanoparticles loaded with batimastat (BB-94) demonstrated selective accumulation at active sites of elastin degradation and markedly reduced aneurysmal expansion in rat AAA models, while equivalent systemic doses were ineffective. PLGA is an FDA-approved nanocarrier platform with documented vascular biocompatibility and sustained biphasic drug-release kinetics suited to targeted vascular delivery [4, 5, 6, 7].
Conclusion: PLGA-based nanovectors represent a scientifically supported platform for the targeted delivery of MMP inhibitors to the pathological vascular wall. Translation of this approach from aortic to cerebral aneurysm models constitutes a logical and warranted research priority.
Keywords: polymeric nanovectors, PLGA, matrix metalloproteinases, MMP-2, MMP-9, batimastat, cerebral aneurysm, targeted drug delivery.