Ocular adverse events associated with anti-VEGF therapy: A pharmacovigilance study of the FDA adverse event reporting system (FAERS).

Background: The purpose of this study is to identify and characterize ocular adverse events (AEs) that are significantly associated with anti-VEGF drugs for treatment of neovascular age-related macular degeneration and compare the differences between each drug, and provide clinical reference. Methods: Ocular AEs submitted to the US Food and Drug Administration were analyzed to map the safety profile of anti-VEGF drugs. The Pharmacovigilance tools used for the quantitative detection of signals were reporting odds ratio and bayesian confidence propagation neural network. Results: A total of 10,608,503 AE reports were retrieved from FAERS, with 20,836 for ranibizumab, 19,107 for aflibercept, and 2,442 for brolucizumab between the reporting period of Q1, 2004 and Q3, 2021. We found and analyzed the different AEs with the strongest signal in each drug-ranibizumab-macular ischaemia (ROR = 205.27, IC-2SD = 3.70), retinal pigment epithelial tear (ROR = 836.54, IC-2SD = 7.19); aflibercept-intraocular pressure increased (ROR = 31.09, IC-2SD = 4.61), endophthalmitis (ROR = 178.27, IC-2SD = 6.70); brolucizumab-retinal vasculitis (ROR = 2930.41, IC-2SD = 7.47) and/or retinal artery occlusion (ROR = 391.11, IC-2SD = 6.10), dry eye (ROR = 12.48, IC-2SD = 2.88). Conclusion: The presence of AEs should bring clinical attention. The use of anti-VEGF drugs should be based on the patient's underlying or present medical condition to reduce any adverse event associated with the treatment.

Biomimetic polysaccharide-cloaked lipidic nanovesicles/microassemblies for improving the enzymatic activity and prolonging the action time for hyperuricemia treatment.

The improvement and maintenance of enzymatic activities represent major challenges. However, to address these we developed novel biomimetic polysaccharide hyaluronan (Hn)-cloaked lipidic nanovesicles (BHLN) and microassemblies (BHLNM) as enzyme carriers that function by entrapping enzymes in the core or by tethering them to the inner/outer surfaces via covalent interactions. The effectiveness of these enzyme carriers was demonstrated through an evaluation of the enzymatic activity and anti-hyperuricemia bioactivity of urate oxidase (also called uricase, Uase). We showed that Uase was effectively loaded within the BHLN/BHLNM (UHLN/UHLNM) and maintained good enzymatic bioactivity through a range of effects, including isolation from the external environment due to the vesicle-carrying (shielding effect), avoidance of recognition by the reticuloendothelial system due to Hn-cloaking (long-term effect), production of beneficial conformational changes (allosteric effect) due to a favorable internal microenvironment of construction and vesicle loading, and stabilization due to the reversible conjugation of Uase or vesicle and serum albumin (deposit effect). UHLN/UHLNM had significantly increased bioavailability (∼533% and ∼331% compared to Uase) and demonstrated greatly improved efficacy, whereby the time required for UHLN/UHLNM to lower the plasma uric acid concentration to a normal level was much shorter than that for free Uase. The interactions of the therapeutic enzyme (Uase), biomimetic membrane components (Hn and phospholipid), and serum albumin were investigated with a fluorescent probe and computational simulations to help understand the superior properties of UHLN/UHLNM.

[Pharmacokinetics and bioequivalence assessment of a self-assembled asparaginase nanocapsule in rats].

OBJECTIVE: To study the pharmacokinetics and bioequivalence of asparaginase loaded in hyaluronic acid-graft-poly(ethylene glycol)/ sulfobutylether-ß-cyclodextrin nanocapsules (AHSP) in SD rats. METHODS: The morphology of AHSP was observed under the transmission electron microscope and the particle size and zeta potential were measured. AHSP and free asparaginase were intravenously injected in rats, and the plasma asparaginase activity was measured at different time points after the injections. The pharmacokinetic parameters were calculated using the software DAS 2.1.1 to assess the bioequivalence of AHSP and free asparaginase. RESULTS: AHSP had an average particle size of 413.80∓10.97 nm with a zeta potential of -20.37∓2.38 mV. The AUC(0-48 h) of AHSP and free asparaginase was 137.34∓1.82 U/mL and 46.38 ∓1.98 U/mL, and their AUC(0-∞) was 164.66∓6.88 U/mL and 51.44∓3.01 U/mL with half-lives of 4.62∓0.60 h and 1.86∓0.38 h, respectively. Compared with free AN, AHSP exhibited increased AUC(0-48 h), AUC(0-∞), and half-life by 2.24, 2.55 and 2.32 folds, respectively. The 90% confidential intervals of AUC(0-48 h), AUC(0-∞) and Cmax of the tested formulation were 75.0%-76.5%, 74.3%-76.1%, and 95.1%-96.7%, respectively. CONCLUSION: AHSP can improve the bioavailability and extend the biological half-life of asparaginase in rats, and AHSP and free asparaginase are not bioequivalent.