Bevacizumab (Avastin®) has been used by ophthalmologists in many countries as an off-label drug for the treatment of wet age-related macular degeneration (AMD). Due to its short half-life necessitating frequent intravitreal injection, a method for sustained delivery is in need. We demonstrated that bevacizumab could be released in a sustained fashion over 90 days from nano- and microspheres fabricated from poly(DL-lactide-co-glycolide) and poly(ethylene glycol)-b-poly(D,L-lactic acid), respectively. The drug release rate could be adjusted by alteration of the drug/polymer ratio. The use of such nano- and microspheres as bevacizumab delivery vehicles may improve the treatment of wet AMD.

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We examined the properties of K+ channels in smooth muscle cells dissociated from human esophagus using patch-clamp recording in the cell-attached configuration. The predominant channel observed had a conductance of 224 ± 4 pS, and current reversal was dependent on K+ concentration. Channel activity was voltage dependent and increased with elevation of intracellular free Ca2+ concentration ([Ca2+]i), consistent with this being the large-conductance Ca2+-dependent K+(KCa) channel. ACh as well as caffeine caused transient increases in KCa channel activity, and the effects of ACh persisted in Ca2+-free solution, indicating that Ca2+ release from stores contributed to channel activation. Simultaneous patch clamp and fluorescence revealed that KCachannel activity was well correlated with elevation of [Ca2+]i. The functional role of KCachannels in esophagus was studied by measuring ACh-induced contraction of strips of muscle. Tetraethylammonium and iberiotoxin, blockers of KCa channels, increased ACh-induced contraction, consistent with a role for K+ channels in limiting excitation and contraction. These studies are the first to characterize KCa channels and their regulation in human esophageal smooth muscle.