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Dry eye disease (DED) is a chronic multifactorial disorder of the ocular surface caused by tear film dysfunction and constitutes one of the most common ocular conditions worldwide. However, its treatment remains unsatisfactory. While artificial tears are commonly used to moisturize the ocular surface, they do not address the underlying causes of DED. Apigenin (APG) is a natural product with anti-inflammatory properties, but its low solubility and bioavailability limit its efficacy. Therefore, a novel formulation of APG loaded into biodegradable and biocompatible nanoparticles (APG-NLC) was developed to overcome the restricted APG stability, improve its therapeutic efficacy, and prolong its retention time on the ocular surface by extending its release. APG-NLC optimization, characterization, biopharmaceutical properties and therapeutic efficacy were evaluated. The optimized APG-NLC exhibited an average particle size below 200 nm, a positive surface charge, and an encapsulation efficiency over 99 %. APG-NLC exhibited sustained release of APG, and stability studies demonstrated that the formulation retained its integrity for over 25 months. In vitro and in vivo ocular tolerance studies indicated that APG-NLC did not cause any irritation, rendering them suitable for ocular topical administration. Furthermore, APG-NLC showed non-toxicity in an epithelial corneal cell line and exhibited fast cell internalization. Therapeutic benefits were demonstrated using an in vivo model of DED, where APG-NLC effectively reversed DED by reducing ocular surface cellular damage and increasing tear volume. Anti-inflammatory assays in vivo also showcased its potential to treat and prevent ocular inflammation, particularly relevant in DED patients. Hence, APG-NLC represent a promising system for the treatment and prevention of DED and its associated inflammation., Competing Interests: Declaration of competing interest Research data and results obtained are protected under patent (PCT/EP2024/052923). LB, ME, MLG and ESL hold the intellectual property of the mentioned patent., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The objective of this study was to understand the influence of the water adsorption and glass transition of matrix formers on redispersibility in water of drug nanocrystals-aggregated particles(NAP) during storage, and the critical storage strategy for NAP powders were determined based on the Guggenheim-Anderson-de Boer (GAB) and the Gordon-Taylor models. Apigenin was used as model drug. Six kinds of matrix formers sucrose(SU), lactose(LA), trehalose(TR), inulin(IN), maltodextrin(MA) and PVPK30(PV) were used to prepare apigenin nanocrystals-aggregated particles (AN-NAPs). The results demonstrated that the adsorption isotherms curves of six kinds of matrix formers based AN-NAPs all showed typical II (S) type adsorption. The water activity significantly influenced the redispersibility of AN-NAP, which could be attributed to the microstructure collapse of amorphous matrix induced by moisture adsorption at high water activity or high moisture. MD based AN-NAP(AN-NAP/MD) exhibited much better redispersibility at high water activity(0.689) compared with the other amorphous matrix formers. MD was able to significantly enlarge the Tg of AN-NAP system and prevent from aggregation of AN-NAP compared to other matrix formers. And the critical water activity and moisture content of AN-NAPs were in the ranges of 0.015-0.545 and 0.0412-0.1508 g water/g dry matter, respectively. Of all amorphous matrix based NAPs, the critical water activity of AN-NAP/MD was the highest (0.545), and the critical moisture content was 0.1003 g water/g dry matter, and followed by TR based on AN-NAP. MD could be used as an excellent matrix former for nanocrystals-aggregated particles during storage. Therefore, the roles of water adsorption and glass transition of matrix formers on redispersibility of drug nanocrystals-aggregated particles during storage was successful elucidated, and the critical storage strategy was proposed based on the GAB model and the Gordon-Taylor model., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The purpose of this study was to develop different injectable nanosized drug delivery systems (NDDSs) i.e. liposome, lipid nanocapsule (LNC) and polymeric nanocapsule (PNC) encapsulating apigenin (AG) and compare their characteristics to identify the nanovector(s) that can deliver the largest quantity of AG while being biocompatible. Two liposomes with different surface characteristics (cationic and anionic), a LNC and a PNC were prepared. A novel tocopherol modified poly(ethylene glycol)-b-polyphosphate block-copolymer was used for the first time for the PNC preparation. The NDDSs were compared by their physicochemical characteristics, AG release, storage stability, stability in serum, complement consumption and toxicity against a human macrovascular endothelial cell line (EAhy926). The diameter and surface charge of the NDDSs were comparable with previously reported injectable nanocarriers. The NDDSs showed good encapsulation efficiency and drug loading. Moreover, the NDDSs were stable during storage and in fetal bovine serum for extended periods, showed low complement consumption and were non-toxic to EAhy926 cells up to high concentrations. Therefore, they can be considered as potential injectable nanocarriers of AG. Due to less pronounced burst effect and extended release characteristics, the nanocapsules could be favorable approaches for achieving prolonged pharmacological activity of AG using injectable NDDS., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The aim of this study is to characterize the in-vitro physicochemical and in-vivo pharmacokinetic properties of the scutellarin-loaded bovine serum albumin nanoparticles (STA-BSA-NPs). STA existed as amorphous form in the nanoparticles. Reconstituted STA-BSA-NPs had an average particle size of 283.4 nm and a zeta potential of +17.95 mV. The in-vitro sustained release profile was well fitted with Weibull distribution model. In comparison to STA solution, STA-BSA-NPs exhibited a significantly higher plasma concentration from 20 min to 6 h after intravenous administration to rats. In addition, significantly higher AUC(0-inf) (2.8-fold), prolonged elimination half-life (4.2-fold) and lower clearance (2.7-fold) were achieved., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The aim of this study was to develop and evaluate a novel topical delivery system for apigenin by using ethosomes. An optimal apigenin-loaded ethosome formulation was identified by means of uniform design experiments. Skin deposition and transdermal flux of apigenin loaded in ethosomes, liposomes, and deformable liposomes were compared in vitro and in vivo. The efficiency of apigenin encapsulation increased with an increase in the amount of phospholipids in ethosome formulations. Moreover, skin deposition and transdermal flux of apigenin improved with an increase in the levels of phospholipids (Lipoid S 75) and short-chain alcohols (propylene glycol and ethanol), but decreased with an increase in the ratio of propylene glycol to ethanol. Profiles of skin deposition versus time for ethosomes varied markedly between in vivo and in vitro studies compared with those of liposomes or deformable liposomes. Optimized ethosomes showed superior skin targeting both in vitro and in vivo. Moreover, they had the strongest effect on reduction of cyclooxygenase-2 levels in mouse skin inflammation induced by ultraviolet B (UVB) light. Therefore, apigenin-loaded ethosomes represent a promising therapeutic approach for the treatment of UVB-induced skin inflammation., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Flavonoids have many positive effects on various cell layers of the skin (e.g. anti-oxidant, anti-allergic and anti-inflammatory effects). However, the limiting factor of the use of flavonoids is their low water solubility. To overcome the poor solubility, apigenin nanosuspensions were prepared using the combination technology (CT), i.e. bead milling and subsequently high pressure homogenization. Distinct reduction in particle size was observed after each bead milling passage resulting in z-average (PCS) of 413 nm and a polydispersity index of 0.202. The LD data showed a similar pattern of particle size reduction reaching a diameter 99% (d(v)99%) of 0.515 μm. The antioxidant capacity of apigenin nanocrystals were almost doubled compared to the original coarse suspension. The developed smartCrystals can be easily incorporated into gels, which makes apigenin nanocrystals available for dermal application as efficient antioxidant., (Copyright © 2011 Elsevier B.V. All rights reserved.)