Mucoadhesive cholesterol-chitosan self-assembled particles for topical ocular delivery of dexamethasone

Dubashynskaya, Natallia V.; Головкин, А. С.; Kudryavtsev, I. V.; Prikhodko, Stanislava; Trulioff, Andrey S.; Bokatyi, Anton N.; Poshina, Daria N.; Raik, Sergei V.; Skorik, Yury A.

doi:10.1016/j.ijbiomac.2020.04.251

Cited by 30 publications

(19 citation statements)

References 33 publications

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“…The washed cells were then resuspended in 50 µL fresh PBS, stained with mouse antibodies against human CD54 (Beckman Coulter Inc., Indianapolis, IN, USA) in the dark for 15 min, and washed again. Finally, the washed cells were resuspended in 100 µL fresh PBS and stained for 5 min with 250 nM PO-PRO-1 iodide (Invitrogen, Thermo Fisher Scientific, USA) and 3 µM DRAQ7 (Beckman Coulter Inc., USA), as described previously [17]. At least 10,000 single THP-1 cells per each sample were acquired.…”

Section: Anti-inflammatory Activity Of the Succs-dex Conjugatesmentioning

confidence: 99%

“…For this reason, an intravitreal dosage form must have a prolonged release profile of active pharmaceutical substances over several months while still maintaining the drug concentration at an adequate therapeutic level [8,11,12]. Current intravitreal drugs include implants (e.g., FDA approved Ozurdex [13]) and various types of polymeric nanoparticles, but many of these implants and nanoparticles consist of nondegradable polymers, and this limits their wide clinical application for controlled drug release [2,3,[14][15][16][17]. The use of various nanoparticles for retinal delivery does not ensure the desired months-long release profile and can also lead to increased intraocular pressure and visual impairment [11].…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and Characterization of Novel Succinyl Chitosan-Dexamethasone Conjugates for Potential Intravitreal Dexamethasone Delivery

Dubashynskaya

Bokatyi

Головкин

et al. 2021

IJMS

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The development of intravitreal glucocorticoid delivery systems is a current global challenge for the treatment of inflammatory diseases of the posterior segment of the eye. The main advantages of these systems are that they can overcome anatomical and physiological ophthalmic barriers and increase local bioavailability while prolonging and controlling drug release over several months to improve the safety and effectiveness of glucocorticoid therapy. One approach to the development of optimal delivery systems for intravitreal injections is the conjugation of low-molecular-weight drugs with natural polymers to prevent their rapid elimination and provide targeted and controlled release. This study focuses on the development of a procedure for a two-step synthesis of dexamethasone (DEX) conjugates based on the natural polysaccharide chitosan (CS). We first used carbodiimide chemistry to conjugate DEX to CS via a succinyl linker, and we then modified the obtained systems with succinic anhydride to impart a negative ζ-potential to the polymer particle surface. The resulting polysaccharide carriers had a degree of substitution with DEX moieties of 2–4%, a DEX content of 50–85 μg/mg, and a degree of succinylation of 64–68%. The size of the obtained particles was 400–1100 nm, and the z-potential was −30 to −33 mV. In vitro release studies at pH 7.4 showed slow hydrolysis of the amide and ester bonds in the synthesized systems, with a total release of 8–10% for both DEX and succinyl dexamethasone (SucDEX) after 1 month. The developed conjugates showed a significant anti-inflammatory effect in TNFα-induced and LPS-induced inflammation models, suppressing CD54 expression in THP-1 cells by 2- and 4-fold, respectively. Thus, these novel succinyl chitosan-dexamethasone (SucCS-DEX) conjugates are promising ophthalmic carriers for intravitreal delivery.

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Section: Anti-inflammatory Activity Of the Succs-dex Conjugatesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis and Characterization of Novel Succinyl Chitosan-Dexamethasone Conjugates for Potential Intravitreal Dexamethasone Delivery

Dubashynskaya

Bokatyi

Головкин

et al. 2021

IJMS

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“…These nanocarriers performed better in terms of drug release behavior and antiinflammatory effects in the guinea pig model compared with micronized gel (Alqurshi et al, 2019). Several studies have attempted to modify polysaccharides simply to obtain various non-covalent interactions (Dubashynskaya N. V. et al, 2020;Liu C.H. et al, 2020).…”

Section: Typical Ocular Polysaccharide-based Nanocarriers and Novel Design Strategiesmentioning

confidence: 99%

Polysaccharide-Based Nanomaterials for Ocular Drug Delivery: A Perspective

Lin

et al. 2020

Front. Bioeng. Biotechnol.

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Ocular drug delivery is one of the most challenging issues in ophthalmology because of the complex physiological structure of the eye. Polysaccharide-based nanomaterials have been extensively investigated in recent years as ideal carriers for enhancing the bioavailability of drugs in the ocular system because of their biocompatibility and drug solubilization. From this perspective, we discuss the structural instability of polysaccharides and its impact on the synthesis process; examine the potential for developing bioactive polysaccharide-based ocular drug nanocarriers; propose four strategies for designing novel drug delivery nanomaterials; and suggest reviewing the behavior of nanomaterials in ocular tissues.

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“…Among natural polymers, natural polysaccharides are widely used because of their diverse functions including biosafety, good tolerance, superior bioavailability and biological activities. More and more evidence indicates that polysaccharide-based nanocarriers have received considerable attention for clinical practice [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Natural Polysaccharide-Based Nanodrug Delivery Systems for Treatment of Diabetes

et al. 2022

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In recent years, natural polysaccharides have been considered as the ideal candidates for novel drug delivery systems because of their good biocompatibility, biodegradation, low immunogenicity, renewable source and easy modification. These natural polymers are widely used in the designing of nanocarriers, which possess wide applications in therapeutics, diagnostics, delivery and protection of bioactive compounds or drugs. A great deal of studies could be focused on developing polysaccharide nanoparticles and promoting their application in various fields, especially in biomedicine. In this review, a variety of polysaccharide-based nanocarriers were introduced, including nanoliposomes, nanoparticles, nanomicelles, nanoemulsions and nanohydrogels, focusing on the latest research progress of these nanocarriers in the treatment of diabetes and the possible strategies for further study of polysaccharide nanocarriers.

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Mucoadhesive cholesterol-chitosan self-assembled particles for topical ocular delivery of dexamethasone

Cited by 30 publications

References 33 publications

Synthesis and Characterization of Novel Succinyl Chitosan-Dexamethasone Conjugates for Potential Intravitreal Dexamethasone Delivery

Synthesis and Characterization of Novel Succinyl Chitosan-Dexamethasone Conjugates for Potential Intravitreal Dexamethasone Delivery

Polysaccharide-Based Nanomaterials for Ocular Drug Delivery: A Perspective

Natural Polysaccharide-Based Nanodrug Delivery Systems for Treatment of Diabetes

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