Collagenase loaded chitosan nanoparticles for digestion of the collagenous scar in liver fibrosis: The effect of chitosan intrinsic collagen binding on the success of targeting

Targeting Activated Hepatic Stellate Cells Using Collagen-Binding Chitosan Nanoparticles for siRNA Delivery to Fibrotic Livers

“…CS-NPs were modified with different densities of the PDGFR-β-binding peptide CIPLPPPSRPFFK [ 18 ] (Biomatik, USA) using the short-chain amine-thiol crosslinker succinimidyl 3-(2-pyridyldithio)propionate) (SPDP) (ThermoFisher Scientific, Schwerte, Germany), via a stepwise approach that was optimized in earlier work from our group [ 20 , 25 ]. Briefly, SPDP was dissolved in dimethyl sulfoxide (DMSO ) and added to CS-NPs at a final concentration of 0.9 mM.…”

“…Briefly, SPDP was dissolved in dimethyl sulfoxide (DMSO ) and added to CS-NPs at a final concentration of 0.9 mM. Successful SPDP tagging to CS-NPs was confirmed using the pyridine-2-thione assay as described before [ 20 , 25 ]. The SPDP-modified NPs were incubated with increasing concentrations of fluorescein labeled CIPLPPPSRPFFK (Biomatik, Wilmington, DE, USA)—with a final concentration of 0.1, 0.15, 0.3 and 0.5 mM peptide—and allowed to react overnight.…”

“…The obtained tissue sections were collected on glass slides, de-paraffinized, stained with hematoxylin and eosin (H&E) for examination under the light microscope [ 30 ]. To determine whether chitosan collagen binding affects the NP in-vivo biodistribution and whether the excess deposition of collagen in fibrotic livers would facilitate NP accumulation in fibrotic livers Collagenase-loaded chitosan nanoparticles were prepared as detailed in earlier work from our group [ 25 ]. The healthy and fibrotic groups were divided each into two groups; the first group received collagenase-NPs intravenously (IV) for one week followed by fluorescent CS-NPs, LP-NPs and HP-NPs, while the second group received PBS instead of collagenase-NPs followed by fluorescent CS-NPs, LP-NPs and HP-NPs.…”

“…Additionally, and highly important in the context of fibrotic diseases, chitosan has been reported to bind and interact with collagen [ 24 ]. We recently demonstrated the ability of small (100 nm) chitosan NPs to accumulate in fibrotic livers following intravenous administration as a function of their collagen binding properties [ 25 ].…”

Preparation and characterization of lamotrigine containing nanocapsules for nasal administration

“…In the literature some articles could be found, where e.g. statin or benziodiazepine containing NCs were investigated via nasal route [36][37][38]. In these studies the researchers aimed to develop and investigate these formulations in vivo and the APIs presented in the brain tissues after nasal administration of NCs, so they could be suitable for the treatment of other diseases.…”