ABSTRACT
Chitosan polymers (Cs), from which microparticles (CsM) may be precipitated to deliver various intracellular payloads, are generally considered biologically inert. We examined the impact of cell culture conditions on CsM size and the effect of chitosan on CD59 expression in primary human smooth muscle cells. We found that particle concentration and incubation time in biological buffers augmented particle size. Between pH 7.0 and pH 7.5, CsM size increased abruptly. We utilized CsM containing a plasmid with a gene for CD59 (pCsM) to transfect cells. Both CD59 mRNA and the number of CD59-positive cells were increased after pCsM treatment. Unexpectedly, CsM also augmented the number of CD59-positive cells. Cs alone enhanced CD59 expression more potently than either pCSM or CsM. This observation strongly suggests that chitosan is in fact bioactive and that chitosan-only controls should be included to avoid misattributing the activity of the delivery agent with that of the payload.
Subject(s)
Chitosan/analogs & derivatives , Nanoparticles/chemistry , Transfection/methods , CD59 Antigens/genetics , CD59 Antigens/metabolism , Cells, Cultured , Humans , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/metabolism , Nanoparticles/adverse effects , Plasmids/genetics , Plasmids/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolismABSTRACT
Alzheimer's disease (AD) is the most common form of dementia, which completely lacks a viable, long-term therapeutic intervention. This is partly due to an incomplete understanding of AD etiology and the possible confounding factors associated with its genotypic and phenotypic heterogeneity. Cerebral amyloid angiopathy (CAA) is a common, yet frequently overlooked, pathology associated with AD. CAA manifests with deposition amyloid-beta (Aß) within the smooth muscle layer of cerebral arteries and arterioles. The role of Aß in AD and CAA pathophysiology has long been controversial. Although it has demonstrated toxicity at super-physiological levels in vitro, Aß load does not necessarily correlate with cognitive demise in humans. In this review, we describe the contributions of CAA to AD pathophysiology and important pathomechanisms that may lead to vascular fragility and hemorrhages. Additionally, we discuss the effect of Aß on smooth muscle cell phenotype and viability, especially in terms of the complement cascade.
