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

2021 ◽  
Vol 22 (20) ◽  
pp. 10960
Author(s):  
Natallia V. Dubashynskaya ◽  
Anton N. Bokatyi ◽  
Alexey S. Golovkin ◽  
Igor V. Kudryavtsev ◽  
Maria K. Serebryakova ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Particle Surface ◽  
In Vitro Release ◽  
Delivery Systems ◽  
Polymer Particle ◽  
Natural Polymers ◽  
Global Challenge ◽  
Natural Polysaccharide ◽  
Intravitreal Dexamethasone

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.

scholarly journals Influence of Oleic Acid on the Rheology and in Vitro Release of Lumiracoxib from Poloxamer Gels

2010 ◽  
Vol 13 (2) ◽  
pp. 286 ◽  
Author(s):  
Tailane Sant´Anna Moreira ◽  
Valéria Pereira De Sousa ◽  
Maria Bernadete Riemma Pierre
Keyword(s):  
Oleic Acid ◽  
Rheological Behavior ◽  
Transdermal Delivery ◽  
In Vitro Release ◽  
Delivery Systems ◽  
Penetration Enhancer ◽  
Release Studies ◽  
Vitro Release ◽  
Gel Transition

Abstract PURPOSE: Transdermal delivery of anti-inflammatory lumiracoxib (LM) could be an interesting strategy to avoid the side effects associated with systemic delivery, but it is ineffective due to the drug poor skin penetration. We have investigated the effects of oleic acid (OA), a lipid penetration enhancer, on the in vitro release of LM from poloxamer-based delivery systems (PBDS). The rheological behavior (shear rate dependent viscosity) and gelation temperature through measurements of optimal sol-gel transition temperatures (Tsol-gel) were also carried out in these systems. METHODS: In vitro release studies of LM from PBDS were performed using cellulose acetate as artificial membrane mounted in a diffusion system. The amount of LM released was divided by exposition area (µg/cm2) and these values were plotted as function of the time (h). The flux of the drug across the membrane (J) was calculated from the slope of the linear portion of the plot and expressed as µg/cm2. h -1. The determination of viscosity was carried out at different shear rates (γ) between 0.1- 1000 S-1 using a parallel plate rheometer. Oscillatory measurements using a cone-plate geometry rheometer surrounded by a double jacket with temperature varying 4-40°C, was used in order to determine Tsol-gel. RESULTS: Increase of both polymer and OA concentrations increases the viscosity of the gels and consequently reduces the in vitro LM release from the PBDS, mainly for gels containing OA at 10.0% compared to other concentrations of the penetration enhancer. Tsol-gel transition temperature was decreased by increasing viscosity; in some cases the formulation was already a gel at room temperature. Rheological studies showed a pseudoplastic behavior, which facilitates the flow and improves the spreading characteristics of the formulations. CONCLUSIONS: Taken together, the results showed that poloxamer gels are good potential delivery systems for LM, leading to a sustained release, and also have appropriate rheological characteristics. Novelty of the work: A transdermal delivery of non-steroidal antinflammatory drugs like lumiracoxib (LM) can be an interesting alternative to the oral route of this drug, since it was recently withdraw of the market due to the liver damage when systemically administered in tablets as dosage form. There are no transdermal formulations of LM and it could be an alternative to treat inflammation caused by arthritis or arthrosis. Then, an adequate delivery system to LM is necessary in order to release the drug properly from the PBDS as well as have good characteristics related to semi-solid preparations for transdermal application, which were evaluated through in vitro release studies and rheological behavior in this paper, respectively.

Development and validation of an in vitro release method for topical particulate delivery systems

2015 ◽  
Vol 485 (1-2) ◽  
pp. 202-214 ◽  
Author(s):  
Maja Lusina Kregar ◽  
Marjana Dürrigl ◽  
Andrea Rožman ◽  
Želimir Jelčić ◽  
Biserka Cetina-Čižmek ◽  
...  
Keyword(s):  
In Vitro Release ◽  
Delivery Systems ◽  
Particulate Delivery ◽  
Development And Validation ◽  
Release Method ◽  
Vitro Release

Calcium phosphate porous pellets as drug delivery systems: Effect of drug carrier composition on drug loading and in vitro release

2012 ◽  
Vol 32 (11) ◽  
pp. 2679-2690 ◽  
Author(s):  
Hiva Baradari ◽  
Chantal Damia ◽  
Maggy Dutreih-Colas ◽  
Etienne Laborde ◽  
Nathalie Pécout ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Calcium Phosphate ◽  
Drug Delivery Systems ◽  
Drug Carrier ◽  
Drug Loading ◽  
In Vitro Release ◽  
Delivery Systems ◽  
Vitro Release

scholarly journals Quaternary Ammonium Chitosans: The Importance of the Positive Fixed Charge of the Drug Delivery Systems

2020 ◽  
Vol 21 (18) ◽  
pp. 6617 ◽  
Author(s):  
Angela Fabiano ◽  
Denise Beconcini ◽  
Chiara Migone ◽  
Anna Maria Piras ◽  
Ylenia Zambito
Keyword(s):  
Drug Delivery ◽  
Quaternary Ammonium ◽  
Drug Delivery Systems ◽  
Ex Vivo ◽  
Delivery Systems ◽  
Fixed Charge ◽  
Innovative Drug ◽  
Natural Polysaccharide ◽  
The Impact

As a natural polysaccharide, chitosan has good biocompatibility, biodegradability and biosecurity. The hydroxyl and amino groups present in its structure make it an extremely versatile and chemically modifiable material. In recent years, various synthetic strategies have been used to modify chitosan, mainly to solve the problem of its insolubility in neutral physiological fluids. Thus, derivatives with negative or positive fixed charge were synthesized and used to prepare innovative drug delivery systems. Positively charged conjugates showed improved properties compared to unmodified chitosan. In this review the main quaternary ammonium derivatives of chitosan will be considered, their preparation and their applications will be described to evaluate the impact of the positive fixed charge on the improvement of the properties of the drug delivery systems based on these polymers. Furthermore, the performances of the proposed systems resulting from in vitro and ex vivo experiments will be taken into consideration, with particular attention to cytotoxicity of systems, and their ability to promote drug absorption.

Dexamethasone Degradation in Aqueous Medium and Implications for Correction of In Vitro Release from Sustained Release Delivery Systems

2019 ◽  
Vol 20 (8) ◽  
Author(s):  
Brock Matter ◽  
Alireza Ghaffari ◽  
David Bourne ◽  
Yan Wang ◽  
Stephanie Choi ◽  
...  
Keyword(s):  
Sustained Release ◽  
Aqueous Medium ◽  
In Vitro Release ◽  
Delivery Systems ◽  
Vitro Release

scholarly journals Okra-Thioglycolic Acid Conjugate—Synthesis, Characterization, and Evaluation as a Mucoadhesive Polymer

Processes ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 316 ◽  
Author(s):  
N. Raghavendra Naveen ◽  
Chakka Gopinath ◽  
Mallesh Kurakula
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Pharmacokinetic Studies ◽  
Natural Polymers ◽  
Covalent Bonds ◽  
Prolonged Contact ◽  
Thiol Functionalization

The success of mucoadhesive drug delivery systems relies on the type of polymer used, which becomes adhesive naturally upon hydration. Intended polymers should be able to maintain prolonged contact with biological membranes, and to protect or cater the drug to a prolonged period. Most of the hydro polymers form weak non-covalent bonds, that hinder localization of dosage forms at specific sites resulting in therapeutic inefficiency. This can be overcome by the thiol functionalization of natural polymers. In the present study, natural okra gum (OG) was extracted, followed by thiolation (TOG) and evaluated for mucoadhesion property and its role in enhancing the efficacy of repaglinide as a model drug (short-acting Type II antidiabetic drug). The thiol functionalization of OG (TOG) was confirmed by a Fourier-transform infrared spectroscopy (FTIR) study that showed a polyhedral to a spherical shape that had a rougher surface. Differential scanning calorimetry (DSC) and X-Ray Diffraction (XRD) studies of TOG indicated a decline in endothermic transition temperature and high crystallinity, respectively, in comparison to OG. CSFR (Crushing Strength: Friability Ratio), weight and thickness variations of repaglinidetablets formulated using TOG were >80% and <2.5% respectively. The highest swelling index (107.89 ± 1.99%) and strong mucoadhesion due to high disulfide bonds were observed for repaglinide TOG tablets in comparison to RG OG tablets. In-vitro release studies indicated a controlled drug release from thiolated formulations proportional to the concentration of thiomers that have a good correlation with in-vivo studies. Pharmacokinetic studies indicated higher AUC (area under the curve), longer t1/2 with thiomers. and Level A IVIV (in vitro in vivo) correlation was established from the bioavailability and dissolution data. Consequently, all the obtained results suggest that thiomers based formulations can be promising drug delivery systems, even in targeting onerous mucosal surfaces like nasal, ocular or vaginal.

scholarly journals Injectable Lipid-Based Depot Formulations: Where Do We Stand?

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 567 ◽  
Author(s):  
Lisa Rahnfeld ◽  
Paola Luciani
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
In Vitro Release ◽  
Delivery Systems ◽  
The Body ◽  
Solid Particles ◽  
Depot Formulation ◽  
Pharmaceutical Ingredients ◽  
Long Acting

The remarkable number of new molecular entities approved per year as parenteral drugs, such as biologics and complex active pharmaceutical ingredients, calls for innovative and tunable drug delivery systems. Besides making these classes of drugs available in the body, injectable depot formulations offer the unique advantage in the parenteral world of reducing the number of required injections, thus increasing effectiveness as well as patient compliance. To date, a plethora of excipients has been proposed to formulate depot systems, and among those, lipids stand out due to their unique biocompatibility properties and safety profile. Looking at the several long-acting drug delivery systems based on lipids designed so far, a legitimate question may arise: How far away are we from an ideal depot formulation? Here, we review sustained release lipid-based platforms developed in the last 5 years, namely oil-based solutions, liposomal systems, in situ forming systems, solid particles, and implants, and we critically discuss the requirements for an ideal depot formulation with respect to the used excipients, biocompatibility, and the challenges presented by the manufacturing process. Finally, we delve into lights and shadows originating from the current setups of in vitro release assays developed with the aim of assessing the translational potential of depot injectables.

In Vitro Release Test of Nano-drug Delivery Systems Based on Analytical and Technological Perspectives

2019 ◽  
Vol 15 (4) ◽  
pp. 373-409 ◽  
Author(s):  
Emirhan Nemutlu ◽  
İpek Eroğlu ◽  
Hakan Eroğlu ◽  
Sedef Kır
Keyword(s):  
Drug Delivery ◽  
Analytical Method ◽  
Drug Delivery Systems ◽  
In Vitro Release ◽  
Delivery Systems ◽  
Method Selection ◽  
Release Test ◽  
Nano Drug Delivery ◽  
Vitro Release

Background:Nanotech products are gaining more attention depending on their advantages for improving drug solubility, maintenance of drug targeting, and attenuation of drug toxicity. In vitro release test is the critical physical parameter to determine the pharmaceutical quality of the product, to monitor formulation design and batch-to-batch variation.Methods:Spectrophotometric and chromatographic methods are mostly used in quantification studies from in vitro release test of nano-drug delivery systems. These techniques have advantages and disadvantages with respect to each other considering dynamic range, selectivity, automation, compatibility with in vitro release media and cost per sample.Results:It is very important to determine the correct kinetic profile of active pharmaceutical substances. At this point, the analytical method used for in vitro release tests has become a very critical parameter to correctly assess the profiles. In this review, we provided an overview of analytical methods applied to the in vitro release assay of various nanopharmaceuticals.Conclusion:This review presents practical direction on analytical method selection for in vitro release test on nanopharmaceuticals. Moreover, precautions on analytical method selection, optimization and validation were discussed.

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