Chitosan/Silver Nanoparticle/Graphene Oxide Nanocomposites with Multi-Drug Release, Antimicrobial, and Photothermal Conversion Functions

Zheng Su; Daye Sun; Li Zhang; Miaomiao He; Yulin Jiang; Bronagh Millar; Paula Douglas; Davide Mariotti; Paul Maguire; Dan Sun

doi:10.3390/ma14092351

Chitosan/Silver Nanoparticle/Graphene Oxide Nanocomposites with Multi-drug Release, Antimicrobial, and Photothermal Conversion Functions

10.20944/preprints202104.0311.v1 ◽

2021 ◽

Author(s):

Zheng Su ◽

Daye Sun ◽

Li Zhang ◽

Miaomiao He ◽

Yulin Jiang ◽

...

Keyword(s):

Silver Nanoparticles ◽

Graphene Oxide ◽

Drug Release ◽

Composite System ◽

Near Infrared ◽

Environment Friendly ◽

Photothermal Conversion ◽

E Coli ◽

Nanocomposite System ◽

Dual Drug

In this work, we designed and fabricated a multifunctional nanocomposite system which consists of chitosan, raspberry-like silver nanoparticles and graphene oxide. Room temperature atmospheric pressure microplasma (RT-APM) process provides a rapid, facile, and environment-friendly method for introducing silver nanoparticles into the composite system. By loading different drugs onto the polymer matrix and/or graphene oxide, our composite can achieve a pH controlled dual drug release with release profile specific to the drugs used. In addition to its strong antibacterial ability against E. coli and S. aureus, our composite also demonstrates excellent photothermal conversion effect under irradiation of near infrared lasers. These unique functionalities point to it’s the potential of nanocomposite system in multiple applications areas such as multimodal therapeutics in healthcare, water treatment, and anti-microbial, etc.

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Dual-Drug-Loaded Silk Fibroin/PLGA Scaffolds for Potential Bone Regeneration Applications

Journal of Nanomaterials ◽

10.1155/2019/8050413 ◽

2019 ◽

Vol 2019 ◽

pp. 1-16 ◽

Cited By ~ 4

Author(s):

Jihang Yao ◽

Yilong Wang ◽

Wendi Ma ◽

Wenying Dong ◽

Mei Zhang ◽

...

Keyword(s):

Drug Release ◽

Sustained Release ◽

Bone Regeneration ◽

Silk Fibroin ◽

Bone Morphogenetic Protein 2 ◽

Burst Release ◽

Nanofiber Membrane ◽

Differentiation Potential ◽

Dual Drug

Developing scaffold materials with excellent biocompatibility, mechanical properties, and controlled drug release properties is vital to tissue engineering. In this study, we fabricated silk fibroin (SF)/poly(lactide-co-glycolide) (PLGA) nanofiber scaffolds containing recombinant human bone morphogenetic protein 2 (rhBMP2) and dexamethasone (DXM) via coaxial electrospinning, which were used in in vitro bone formation with rat bone marrow mesenchymal stem cells (rBMSCs). An in vitro drug release study was adopted to evaluate the sustained release potential of the core-shell structured nanofibers. Furthermore, we detected the potential of the SF/PLGA nanofiber membrane in vitro. In vitro studies showed that rhBMP2 still remained active on the nanofiber membrane. In addition, the dual-drug-loaded nanofiber membrane showed an early burst release of DXM and late sustained release of rhBMP2. rhBMP2 and DXM exhibited strong osteogenic differentiation potential when they acted on rBMSCs. Therefore, the SF/PLGA nanofiber membrane loaded with rhBMP2 and DXM has great potential for the enhancement of bone regeneration.

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Asymmetric Flow Field-Flow Fractionation (AF4) with Fluorescence Detection for Direct, Real-Time, Size-Resolved Measurements of Drug Release from Polymeric Nanoparticles

10.26434/chemrxiv.12746939.v1 ◽

2020 ◽

Author(s):

Sheyda Shakiba ◽

Carlos E. Astete ◽

Rafael Cueto ◽

Debora F. Rodrigues ◽

Cristina M. Sabliov ◽

...

Keyword(s):

Drug Release ◽

Flow Field ◽

Fluorescence Detection ◽

Release Rate ◽

Polymeric Nanoparticles ◽

Burst Release ◽

Field Flow Fractionation ◽

Asymmetric Flow ◽

Flow Fractionation ◽

Release Profiles

Polymeric nanoparticles (NPs) are typically designed to enhance the efficiency of drug delivery by controlling the drug release rate. Hence, it is critical to obtain an accurate drug release profile. This study presents the first application of asymmetric flow field-flow fractionation (AF4) with fluorescence detection (FLD) to characterize release profiles of fluorescent drugs from polymeric NPs, specifically poly lactic-co-glycolic acid NPs loaded with enrofloxacin (PLGA-Enro NPs). In contrast to traditional release measurements requiring separation of entrapped and dissolved drugs (typically by dialysis) prior to quantification, AF4-FLD provides in situ purification of the NPs from unincorporated drugs, along with direct measurement of the entrapped drug. Size distributions and shape factors are simultaneously obtained by online dynamic and multi-angle light scattering detectors. The AF4-FLD and dialysis approaches were compared to evaluate drug release from PLGA-Enro NPs containing a high proportion (≈ 88%) of unincorporated (burst release) drug at three different temperatures spanning the glass transition temperature (30 °C for PLGA-Enro NPs). The AF4-FLD analysis was able to identify size-dependent release rates across the entire continuous NP size distribution, with smaller NPs showing faster release. The AF4-FLD method also clearly captured the expected temperature dependence of the drug release (from almost no release at 20 °C to rapid release at 37 °C). In contrast, dialysis was not able to distinguish these differences in the extent or rate of release of the entrapped drug because of interferences from the burst release background, as well as the dialysis lag time. A mechanistic diffusion model that integrates data from both AF4-FLD and dialysis further supported the advantages of AF4-FLD to capture the true release rate of entrapped drug and avoid artifacts observed in dialysis. Overall, this study demonstrates the novel application and unique advantages of AF4-FLD methods to obtain direct, size-resolved release profiles of fluorescent drugs from polymeric NPs.

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Electrospun Chitosan/Poly (Vinyl Alcohol)/Graphene Oxide Nanofibrous Membrane with Ciprofloxacin Antibiotic Drug for Potential WoundDressing Application

International Journal of Molecular Sciences ◽

10.3390/ijms20184395 ◽

2019 ◽

Vol 20 (18) ◽

pp. 4395 ◽

Cited By ~ 11

Author(s):

Yang ◽

Zhang ◽

Zhang

Keyword(s):

Graphene Oxide ◽

Drug Release ◽

Vinyl Alcohol ◽

Poly Vinyl Alcohol ◽

Burst Release ◽

Drug Release Profile ◽

Electrospinning Technique ◽

Antibiotic Drugs ◽

Antibiotic Drug ◽

Nanofibrous Membranes

In this paper, nanofibrous membranes based on chitosan (CS), poly (vinyl alcohol) (PVA) and graphene oxide (GO) composites, loaded with antibiotic drugs, such as Ciprofloxacin (Cip) and Ciprofloxacin hydrochloride (CipHcl) were prepared via the electrospinning technique. The uniform and defect-free CS/PVA nanofibers were obtained and GO nanosheets, shaping spindle and spherical, were partially embedded into nanofibers. Besides, the antibiotic drugs were effectively loaded into the nanofibers and part of which were absorbed into GO nanosheets. Intriguingly, the release of the drug absorbed in GO nanosheets regulated the drug release profile trend, avoiding the “burst” release of drug at the release initial stage, and the addition of GO slightly improved the drug release ratio. Nanofibrous membranes showed the significantly enhanced antibacterial activity against Escherichia coli, Staphylococcus aureus and Bacillus subtilis after the addition of antibiotic drug. Moreover, the drug-loaded nanofibrous membranes exhibited excellent cytocompatibility with Melanoma cells, indicative to the great potential potential for applications in wound dressing.

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Preparation, Optimization, and Evaluation of Epichlorohydrin Cross-Linked Enset (Ensete ventricosum (Welw.) Cheeseman) Starch as Drug Release Sustaining Excipient in Microsphere Formulation

BioMed Research International ◽

10.1155/2020/2147971 ◽

2020 ◽

Vol 2020 ◽

pp. 1-19

Author(s):

Desta Tesfay ◽

Solomon Abrha ◽

Zewdu Yilma ◽

Gebremariam Woldu ◽

Fantahun Molla

Keyword(s):

Drug Release ◽

Central Composite Design ◽

Release Rate ◽

Fickian Diffusion ◽

Cross Linking ◽

Release Mechanism ◽

Burst Release ◽

Drug Release Rate ◽

Ensete Ventricosum ◽

Central Composite

Ensete ventricosum (Welw.) cheeseman which belongs to the family of Musaceae is one of the main sources of starch in Ethiopia. This study aimed at evaluating epichlorohydrin cross-linked enset starch as a drug release sustaining excipient in microsphere formulations of theophylline. Extracted enset starch was cross-linked using epichlorohydrin as a cross-linking agent. The effect of cross-linker concentration, cross-linking duration, and cross-linking temperature on the degree of cross-linking and release rate of microspheres prepared by emulsion solvent evaporation method was investigated using the two-level full factorial design. Accordingly, the concentration of epichlorohydrin and duration of cross-linking were the most significant factors affecting both the degree of cross-linking and drug release rate. Thus, the effects of these two factors were further studied and optimized using the central composite design. As per the numerical method of central composite design, the optimal points were obtained at epichlorohydrin concentration of 13.70% and cross-linking time of 3.82 h. Under these optimal conditions, the model predicts the degree of cross-linking of 74.70% and drug release rate of 28.00 h1/2. The validity of these optimal points was confirmed experimentally. The microspheres of the optimum formulation also exhibited minimum burst release with sustained release for 12 h. Besides, the optimized formulation followed the Higuchi square root kinetic model with non-Fickian diffusion release mechanism. The finding of this study suggested that cross-linked enset starch can be used as an alternative drug-release-sustaining pharmaceutical excipient in microsphere formulation.

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Design and Pharmaceutical Evaluation of a Nano-Enabled Crosslinked Multipolymeric Scaffold for Prolonged Intracranial Release of Zidovudine

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/j3r88k ◽

2013 ◽

Vol 16 (3) ◽

pp. 470 ◽

Cited By ~ 1

Author(s):

Sheri-Lee Harilall ◽

Yahya E Choonara ◽

Girish Modi ◽

Lomas K Tomar ◽

Charu Tyagi ◽

...

Keyword(s):

Electron Microscopy ◽

Drug Delivery ◽

Controlled Release ◽

Drug Release ◽

Release Rate ◽

Entrapment Efficiency ◽

Drug Uptake ◽

Aids Dementia Complex ◽

Burst Release ◽

Potential Candidate

Purpose. Nanomedicine explores and allows for the development of drug delivery devices with superior drug uptake, controlled release and fewer drug side-effects. This study explored the use of nanosystems to formulate an implantable drug delivery device capable of sustained zidovudine release over a prolonged period. Methods. Pectin and alginate nanoparticles were prepared by applying a salting out and controlled gelification approach, respectively. The nanoparticles were characterized by attenuated total reflectance-fourier transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and dynamic light scattering (DLS) and were further evaluated for zidovudine (AZT) entrapment efficiency. Multipolymeric scaffolds were prepared by crosslinking carboxymethyl cellulose, polyethylene oxide and epsilon caprolactone for entrapment of zidovudine-loaded alginate nanoparticles to impart enhanced controlled release of zidovudine over the time period. Swelling and textural analysis were conducted on the scaffolds. Prepared scaffolds were treated with hydrochloric acid (HCl) to reduce the swelling of matrix in the hydrated environment thereby further controlling the drug release. Drug release studies in phosphate buffered saline (pH 7.4, 37°C) were undertaken on both zidovudine-loaded nanoparticles and native scaffolds containing alginate nanoparticles. Results. A higher AZT entrapment efficiency was observed in alginate nanoparticles. Biphasic release was observed with both nanoparticle formulations, exhibiting an initial burst release of drug within hours of exposure to PBS, followed by a constant release rate of AZT over the remaining 30 days of nanoparticle analysis. Exposure of the scaffolds to HCl served to reduce the drug release rate from the entrapped alginate nanoparticles and extended the AZT release up to 30 days. Conclusions. The crosslinked multipolymeric scaffold loaded with alginate nanoparticles and treated with 1% HCl showed the potential for prolonged delivery of zidovudine over a period of 30 days and therefore may be a potential candidate for use as an implantable device in treating Aids Dementia Complex. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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Asymmetric Flow Field-Flow Fractionation (AF4) with Fluorescence Detection for Direct, Real-Time, Size-Resolved Measurements of Drug Release from Polymeric Nanoparticles

10.26434/chemrxiv.12746939 ◽

2020 ◽

Author(s):

Sheyda Shakiba ◽

Carlos E. Astete ◽

Rafael Cueto ◽

Debora F. Rodrigues ◽

Cristina M. Sabliov ◽

...

Keyword(s):

Drug Release ◽

Flow Field ◽

Fluorescence Detection ◽

Release Rate ◽

Polymeric Nanoparticles ◽

Burst Release ◽

Field Flow Fractionation ◽

Asymmetric Flow ◽

Flow Fractionation ◽

Release Profiles

Polymeric nanoparticles (NPs) are typically designed to enhance the efficiency of drug delivery by controlling the drug release rate. Hence, it is critical to obtain an accurate drug release profile. This study presents the first application of asymmetric flow field-flow fractionation (AF4) with fluorescence detection (FLD) to characterize release profiles of fluorescent drugs from polymeric NPs, specifically poly lactic-co-glycolic acid NPs loaded with enrofloxacin (PLGA-Enro NPs). In contrast to traditional release measurements requiring separation of entrapped and dissolved drugs (typically by dialysis) prior to quantification, AF4-FLD provides in situ purification of the NPs from unincorporated drugs, along with direct measurement of the entrapped drug. Size distributions and shape factors are simultaneously obtained by online dynamic and multi-angle light scattering detectors. The AF4-FLD and dialysis approaches were compared to evaluate drug release from PLGA-Enro NPs containing a high proportion (≈ 88%) of unincorporated (burst release) drug at three different temperatures spanning the glass transition temperature (30 °C for PLGA-Enro NPs). The AF4-FLD analysis was able to identify size-dependent release rates across the entire continuous NP size distribution, with smaller NPs showing faster release. The AF4-FLD method also clearly captured the expected temperature dependence of the drug release (from almost no release at 20 °C to rapid release at 37 °C). In contrast, dialysis was not able to distinguish these differences in the extent or rate of release of the entrapped drug because of interferences from the burst release background, as well as the dialysis lag time. A mechanistic diffusion model that integrates data from both AF4-FLD and dialysis further supported the advantages of AF4-FLD to capture the true release rate of entrapped drug and avoid artifacts observed in dialysis. Overall, this study demonstrates the novel application and unique advantages of AF4-FLD methods to obtain direct, size-resolved release profiles of fluorescent drugs from polymeric NPs.

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Influence of Formulation Variables and Processing Techniques on Drug Release from Carbopol-971 based Matrix Tablets of Cinnarizine and Nimodipine.

International Journal of Drug Delivery Technology ◽

10.25258/ijddt.v2i1.8840 ◽

2010 ◽

Vol 2 (1) ◽

Author(s):

Singh K. ◽

Pandit K. ◽

Mishra N.

Keyword(s):

Drug Release ◽

Release Rate ◽

Polymer Concentration ◽

Matrix Tablets ◽

Wet Granulation ◽

Weight Variation ◽

Diffusion Controlled ◽

The Matrix ◽

Processing Techniques ◽

Formulation Variables

The matrix tablets of cinnarizine and nimodipine were prepared with varying ratio of Carbopol- 971P and co-excipients of varying hydrophilicity (i.e. dicalcium phosphate and spray dried lactose) by direct compression and wet granulation using alcoholic mucilage. The prepared tablets were evaluated for weight variation, hardness and friability. The influence of concentration of the matrix forming material and co-excipients on the release rate of the drug was studied. The release rate of Cinnarizine (more soluble drug) from tablets followed diffusion controlled mechanism whereas for nimodipine (less soluble drug), the drug release followed case-II or super case- II transport mechanism based on Korsmeyer- Peppas equation. The results indicated that the drug release from matrix tablets was increases with increase in hydrophilicity of drug and co-excipients. The release of drug also increased with thermal treatment and decreasing polymer concentration.

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Reducing the Risk in Controlled Drug Release by Using Tannic Acid in Liposomal Formulations

Revista de Chimie ◽

10.37358/rc.17.12.6008 ◽

2018 ◽

Vol 68 (12) ◽

pp. 2925-2918

Author(s):

Gabriela Cioca ◽

Maricel Agop ◽

Marcel Popa ◽

Simona Bungau ◽

Irina Butuc

Keyword(s):

Drug Release ◽

Tannic Acid ◽

Release Rate ◽

Controlled Drug Release ◽

Toxicity Threshold ◽

Release System ◽

Liposomal Formulations ◽

Cross Linker ◽

Natural Cross

One of the main challenges in designing a release system is the possibility to control the release rate in order to maintain it at a constant value below a defined limit, to avoid exceeding the toxicity threshold. We propose a method of overcoming this difficulty by introducing the drug into liposomes, prior to its inclusion in the hydrogel. Furthermore, a natural cross linker (as is tannic acid) is used, instead of the toxic cross linkers commonly used, thus reducing the toxicity of the release system as a whole.

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Utilization of a Single Experimental Design for the Optimization of Furosemide Modified-Release Tablet Formulations

Current Drug Delivery ◽

10.2174/1567201816666191029130324 ◽

2019 ◽

Vol 16 (10) ◽

pp. 931-939

Author(s):

Marilena Vlachou ◽

Angeliki Siamidi ◽

Yannis Dotsikas

Keyword(s):

Experimental Design ◽

Drug Release ◽

Burst Release ◽

Dissolution Profile ◽

Modified Release ◽

Lactose Monohydrate ◽

Bilayer Tablets ◽

Combined Design ◽

Tablet Formulations ◽

Optimal Combined Design

Background: The loop diuretic drug furosemide is widely used for the treatment of edema in various conditions, such as pulmonary, cardiac and hepatic edema, as well as cardiac infarction. Furosemide, due to its poor water solubility and low bioavailability after oral administration of conventional dosage form, is categorized as class IV in the biopharmaceutical classification system. Objective: In the case of furosemide, this release profile is responsible for various physiological problems, acute diuresis being the most serious. This adverse effect can be circumvented by the modified release of furosemide from tablet formulations compared to those forms designed for immediate release. Method: In this report, a D-optimal combined experimental design was applied for the development of furosemide containing bilayer and compression coated tablets, aiming at lowering the drug’s burst release in the acidic environment of the stomach. A D-optimal combined design was selected in order to include all requirements in one design with many levels for the factors examined. The following responses were selected as the ones reflecting better criteria for the desired drug release: dissolution at 120 min (30-40%), 300 min (60-70%) and 480 min >95%. The new formulations, suggested by the Doptimal combined design, incorporated different grades of Eudragit ® polymers (Eudragit® E100 and Eudragit® L100-55), lactose monohydrate and HPMC K15M. The dissolution profile of furosemide from these systems was probed via in vitro dissolution experiments in buffer solutions simulating the pH of the gastrointestinal tract. Results: The results indicate that the use of Eudragit® E100 in conjunction with lactose monohydrate led to 21.32-40.85 % drug release, in the gastric medium, in both compression-coated and bilayer tablets. This is lower than the release of the mainstream drug Lasix® (t=120 min, 44.5% drug release), implying longer gastric retention and drug waste minimization. Conclusion: Furosemide’s release in the intestinal environment, from compression coated tablets incorporating Eudragit® L100-55 and HPMC K15M in the inner core or one of the two layers of the bilayer tablets, was delayed, compared to Lasix®

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