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16 pages, 3154 KiB

Open AccessArticle

Synthesis and Characterization of Ciprofloxacin Loaded Star-Shaped Polycaprolactone–Polyethylene Glycol Hydrogels for Oral Delivery

by Wan Khartini Wan Abdul Khodir, Mohamad Wafiuddin Ismail, Shafida Abd Hamid, Rusli Daik, Deny Susanti, Muhammad Taher and Vincenzo Guarino

Micromachines 2023, 14(7), 1382; https://doi.org/10.3390/mi14071382 - 6 Jul 2023

Viewed by 1846

Abstract

The administration of poorly water-soluble drugs represents a relevant problem due to the low body fluids transport efficiency through hydrophilic hydrogels. Star-shaped co-polymers, i.e., amphiphilic polymers such as those with a hydrophobic core and a hydrophilic outer shell, can be used to improve [...] Read more.

The administration of poorly water-soluble drugs represents a relevant problem due to the low body fluids transport efficiency through hydrophilic hydrogels. Star-shaped co-polymers, i.e., amphiphilic polymers such as those with a hydrophobic core and a hydrophilic outer shell, can be used to improve weak interactions with drugs, with relevant benefits in terms of administration and controlled delivery. In this work, two different co-polymers, four-arm star-shaped PCL–PEG and six-arm star-shaped PCL–PEG, were synthesized via ring-opening polymerization to be loaded with ciprofloxacin. ¹H-NMR and FTIR analyses confirmed that PCL arms were successfully grafted to the mPEG backbone, while DSC analysis indicated similar crystallinity and melting point, ranging from 56 to 60 °C, independent of the different co-polymer architecture. Therefore, both star-shaped PCL-PEGs were investigated as cargo device for ciprofloxacin. No significant differences were observed in terms of drug entrapment efficiency (>95%) and drug release, characterized by a pronounced burst followed by a slow sustained release, only slightly affected by the co-polymer architecture. This result was also confirmed with curve fitting via the Korsmeyer–Peppas model. Lastly, good antibacterial properties and biocompatibility exhibited in both star-shaped PCL–PEG co-polymers suggest a promising use for oral delivery applications. Full article

(This article belongs to the Special Issue Advanced Functional Materials and 3D Printing for Tissue Engineering and Drug Delivery Applications)

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16 pages, 1778 KiB

Open AccessArticle

Super-Macroporous Pulluan Cryogels as Controlled Active Delivery Systems with Controlled Degradability

by Betul Ari, Mehtap Sahiner, Selin Sagbas Suner, Sahin Demirci and Nurettin Sahiner

Micromachines 2023, 14(7), 1323; https://doi.org/10.3390/mi14071323 - 28 Jun 2023

Cited by 2 | Viewed by 1579

Abstract

Here, super-macroporous cryogel from a natural polysaccharide, pullulan was synthesized using a cryo-crosslinking technique with divinyl sulfone (DVS) as a crosslinker. The hydrolytic degradation of the pullulan cryogel in various simulated body fluids (pH 1.0, 7.4, and 9.0 buffer solutions) was evaluated. It [...] Read more.

Here, super-macroporous cryogel from a natural polysaccharide, pullulan was synthesized using a cryo-crosslinking technique with divinyl sulfone (DVS) as a crosslinker. The hydrolytic degradation of the pullulan cryogel in various simulated body fluids (pH 1.0, 7.4, and 9.0 buffer solutions) was evaluated. It was observed that the pullulan cryogel degradation was much faster in the pH 9 buffer solution than the pH 1.0 and 7.4 buffer solutions in the same time period. The weight loss of the pullulan cryogel at pH 9.0 within 28 days was determined as 31% ± 2%. To demonstrate the controllable drug delivery potential of pullulan cryogels via degradation, an antibiotic, ciprofloxacin, was loaded into pullulan cryogels (pullulan-cipro), and the loading amount of drug was calculated as 105.40 ± 2.6 µg/mg. The release of ciprofloxacin from the pullulan-cipro cryogel was investigated in vitro at 37.5 °C in physiological conditions (pH 7.4). The amount of drug released within 24 h was determined as 39.26 ± 3.78 µg/mg, which is equal to 41.38% ± 3.58% of the loaded drug. Only 0.1 mg of pullulan-cipro cryogel was found to inhibit half of the growing Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) colonies for 10 min and totally eradicated within 2 h by the release of the loaded antibiotic. No significant toxicity was determined on L929 fibroblast cells for 0.1 mg drug-loaded pullulan cryogel. In contrast, even 1 mg of drug-loaded pullulan cryogel revealed slight toxicity (e.g., 66% ± 9% cell viability) because of the high concentration of released drug. Full article

(This article belongs to the Special Issue Advanced Functional Materials and 3D Printing for Tissue Engineering and Drug Delivery Applications)

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9 pages, 1909 KiB

Open AccessArticle

3D Scaffolds Fabrication via Bicomponent Microgels Assembly: Process Optimization and In Vitro Characterization

by Iriczalli Cruz-Maya and Vincenzo Guarino

Micromachines 2022, 13(10), 1726; https://doi.org/10.3390/mi13101726 - 12 Oct 2022

Cited by 2 | Viewed by 1749

Abstract

In the last decade, different technological approaches have been proposed for the fabrication of 3D models suitable to evaluate in vitro cell response. Among them, electro fluid dynamic atomization (EFDA) belonging to the family of electro-assisted technologies allows for the dropping of polysaccharides [...] Read more.

In the last decade, different technological approaches have been proposed for the fabrication of 3D models suitable to evaluate in vitro cell response. Among them, electro fluid dynamic atomization (EFDA) belonging to the family of electro-assisted technologies allows for the dropping of polysaccharides and/or proteins solutions to produce micro-scaled hydrogels or microgels with the peculiar features of hydrogel-like materials (i.e., biocompatibility, wettability, swelling). In this work, a method to fabricate 3D scaffolds by the assembly of bicomponent microgels made of sodium alginate and gelatin was proposed. As first step, optical and scanning electron microscopy with the support of image analysis enabled to explore the basic properties of single blocks in terms of correlation between particle morphology and process parameters (i.e., voltage, flow rate, electrode gap, and needle diameter). Chemical analysis via ninhydrin essays and FTIR analysis confirmed the presence of gelatin, mostly retained by physical interactions into the alginate network mediated by electrostatic forces. In vitro tests confirmed the effect of biochemical signals exerted by the protein on the biological response of hMSCs cultured onto the microgels surface. Hence, it is concluded that alginate/gelatin microgels assemblies can efficiently work as 3D scaffolds able to support in vitro cells functions, thus providing a friendly microenvironment to investigate in vitro cell interactions. Full article

(This article belongs to the Special Issue Advanced Functional Materials and 3D Printing for Tissue Engineering and Drug Delivery Applications)

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11 pages, 1818 KiB

Open AccessArticle

Co-Encapsulation of Paclitaxel and JQ1 in Zein Nanoparticles as Potential Innovative Nanomedicine

by Marilena Celano, Agnese Gagliardi, Valentina Maggisano, Nicola Ambrosio, Stefania Bulotta, Massimo Fresta, Diego Russo and Donato Cosco

Micromachines 2022, 13(10), 1580; https://doi.org/10.3390/mi13101580 - 22 Sep 2022

Cited by 6 | Viewed by 2060

Abstract

The manuscript describes the development of zein nanoparticles containing paclitaxel (PTX) and the bromo-and extra-terminal domain inhibitor (S)-tertbutyl2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno(3,2-f)(1,2,4)triazolo(4,3-a)(1,4)diazepin-6-yl)acetate (JQ1) together with their cytotoxicity on triple-negative breast cancer cells. The rationale of this association is that of exploiting different types of cancer cells as [...] Read more.

The manuscript describes the development of zein nanoparticles containing paclitaxel (PTX) and the bromo-and extra-terminal domain inhibitor (S)-tertbutyl2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno(3,2-f)(1,2,4)triazolo(4,3-a)(1,4)diazepin-6-yl)acetate (JQ1) together with their cytotoxicity on triple-negative breast cancer cells. The rationale of this association is that of exploiting different types of cancer cells as targets in order to obtain increased pharmacological activity with respect to that exerted by the single agents. Zein, a protein found in the endosperm of corn, was used as a biomaterial to obtain multidrug carriers characterized by mean sizes of ˂200 nm, a low polydispersity index (0.1–0.2) and a negative surface charge. An entrapment efficiency of ~35% of both the drugs was obtained when 0.3 mg/mL of the active compounds were used during the nanoprecipitation procedure. No adverse phenomena such as sedimentation, macro-aggregation or flocculation occurred when the nanosystems were heated to 37 °C. The multidrug nanoformulation demonstrated significant in vitro cytototoxic activity against MDA-MB-157 and MDA-MB-231 cancer cells by MTT-test and adhesion assay which was stronger than that of the compounds encapsulated as single agents. The results evidence the potential application of zein nanoparticles containing PTX and JQ1 as a novel nanomedicine. Full article

(This article belongs to the Special Issue Advanced Functional Materials and 3D Printing for Tissue Engineering and Drug Delivery Applications)

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16 pages, 3787 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Rapid and Continuous Cryopreservation of Stem Cells with a 3D Micromixer

by Lin Ding, Sajad Razavi Bazaz, Jesus Shrestha, Hoseyn A. Amiri, Sima Mas-hafi, Balarka Banerjee, Graham Vesey, Morteza Miansari and Majid Ebrahimi Warkiani

Micromachines 2022, 13(9), 1516; https://doi.org/10.3390/mi13091516 - 13 Sep 2022

Cited by 6 | Viewed by 2986

Abstract

Cryopreservation is the final step of stem cell production before the cryostorage of the product. Conventional methods of adding cryoprotecting agents (CPA) into the cells can be manual or automated with robotic arms. However, challenging issues with these methods at industrial-scale production are [...] Read more.

Cryopreservation is the final step of stem cell production before the cryostorage of the product. Conventional methods of adding cryoprotecting agents (CPA) into the cells can be manual or automated with robotic arms. However, challenging issues with these methods at industrial-scale production are the insufficient mixing of cells and CPA, leading to damage of cells, discontinuous feeding, the batch-to-batch difference in products, and, occasionally, cross-contamination. Therefore, the current study proposes an alternative way to overcome the abovementioned challenges; a highly efficient micromixer for low-cost, continuous, labour-free, and automated mixing of stem cells with CPA solutions. Our results show that our micromixer provides a more homogenous mixing of cells and CPA compared to the manual mixing method, while the cell properties, including surface markers, differentiation potential, proliferation, morphology, and therapeutic potential, are well preserved. Full article

(This article belongs to the Special Issue Advanced Functional Materials and 3D Printing for Tissue Engineering and Drug Delivery Applications)

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16 pages, 4834 KiB

Open AccessArticle

Evaluation of 3D Printability and Biocompatibility of Microfluidic Resin for Fabrication of Solid Microneedles

by Atabak Ghanizadeh Tabriz, Beatriz Viegas, Michael Okereke, Md Jasim Uddin, Elena Arribas Lopez, Nazanin Zand, Medhavi Ranatunga, Giulia Getti and Dennis Douroumis

Micromachines 2022, 13(9), 1368; https://doi.org/10.3390/mi13091368 - 23 Aug 2022

Cited by 22 | Viewed by 3953

Abstract

In this study, we have employed Digital Light Processing (DLP) printing technology for the fabrication of solid microneedle (MN) arrays. Several arrays with various geometries, such as cones, three-sided pyramids and four-sided pyramids, with different height to aspect ratios of 1:1, 2:1 and [...] Read more.

In this study, we have employed Digital Light Processing (DLP) printing technology for the fabrication of solid microneedle (MN) arrays. Several arrays with various geometries, such as cones, three-sided pyramids and four-sided pyramids, with different height to aspect ratios of 1:1, 2:1 and 3:1, were printed. Post-processing curing optimizations showed that optimal mechanical properties of the photocurable resin were obtained at 40 °C and 60 min. Ex vivo skin studies showed that piercing forces, penetration depth and penetration width were affected by the MN geometry and height to aspect ratio. Cone-shaped MNs required lower applied forces to penetrate skin and showed higher penetration depth with increasing height to aspect ratio, followed by three-sided and four-sided printed arrays. Cytotoxicity studies presented 84% cell viability of human fibroblasts after 2.5 h, suggesting the very good biocompatibility of the photocurable resin. Overall, DLP demonstrated excellent printing capacity and high resolution for a variety of MN designs. Full article

(This article belongs to the Special Issue Advanced Functional Materials and 3D Printing for Tissue Engineering and Drug Delivery Applications)

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19 pages, 6548 KiB

Open AccessArticle

Design and Prototype Fabrication of a Cost-Effective Microneedle Drug Delivery Apparatus Using Fused Filament Fabrication, Liquid Crystal Display and Semi-Solid Extrusion 3D Printing Technologies

by Petros Papadimitriou, Eleftherios G. Andriotis, Dimitrios Fatouros and Dimitrios Tzetzis

Micromachines 2022, 13(8), 1319; https://doi.org/10.3390/mi13081319 - 15 Aug 2022

Cited by 10 | Viewed by 3996

Abstract

The current study describes the design of a cost-effective drug delivery apparatus that can be manufactured, assembled, and utilized as easily and quickly as possible, minimizing the time and expense of the supply chain. This apparatus could become a realistic alternative method of [...] Read more.

The current study describes the design of a cost-effective drug delivery apparatus that can be manufactured, assembled, and utilized as easily and quickly as possible, minimizing the time and expense of the supply chain. This apparatus could become a realistic alternative method of providing a vaccine or drug in harsh circumstances, including humanitarian disasters or a lack of medical and nursing staff, conditions that are frequently observed in developing countries. Simultaneously, with the use of microneedles (MNs), the apparatus can benefit from the numerous advantages offered by them during administration. The hollow microneedles in particular are internally perforated and are capable of delivering the active substance to the skin. The apparatus was designed with appropriate details in computer aided design software, and various 3D printing technologies were utilized in order to fabricate the prototype. The parts that required minimum accuracy, such as the main body of the apparatus, were fabricated with fused filament fabrication. The internal parts and the hollow microneedles were fabricated with liquid crystal display, and the substance for the drug loading carrier, which was an alginate gel cylinder, was fabricated with semi-solid extrusion 3D printing. Full article

(This article belongs to the Special Issue Advanced Functional Materials and 3D Printing for Tissue Engineering and Drug Delivery Applications)

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Review

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54 pages, 2876 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Sustained Drug Release from Smart Nanoparticles in Cancer Therapy: A Comprehensive Review

by Xue Bai, Zara L. Smith, Yuheng Wang, Sam Butterworth and Annalisa Tirella

Micromachines 2022, 13(10), 1623; https://doi.org/10.3390/mi13101623 - 28 Sep 2022

Cited by 55 | Viewed by 7292

Abstract

Although nanomedicine has been highly investigated for cancer treatment over the past decades, only a few nanomedicines are currently approved and in the market; making this field poorly represented in clinical applications. Key research gaps that require optimization to successfully translate the use [...] Read more.

Although nanomedicine has been highly investigated for cancer treatment over the past decades, only a few nanomedicines are currently approved and in the market; making this field poorly represented in clinical applications. Key research gaps that require optimization to successfully translate the use of nanomedicines have been identified, but not addressed; among these, the lack of control of the release pattern of therapeutics is the most important. To solve these issues with currently used nanomedicines (e.g., burst release, systemic release), different strategies for the design and manufacturing of nanomedicines allowing for better control over the therapeutic release, are currently being investigated. The inclusion of stimuli-responsive properties and prolonged drug release have been identified as effective approaches to include in nanomedicine, and are discussed in this paper. Recently, smart sustained release nanoparticles have been successfully designed to safely and efficiently deliver therapeutics with different kinetic profiles, making them promising for many drug delivery applications and in specific for cancer treatment. In this review, the state-of-the-art of smart sustained release nanoparticles is discussed, focusing on the design strategies and performances of polymeric nanotechnologies. A complete list of nanomedicines currently tested in clinical trials and approved nanomedicines for cancer treatment is presented, critically discussing advantages and limitations with respect to the newly developed nanotechnologies and manufacturing methods. By the presented discussion and the highlight of nanomedicine design criteria and current limitations, this review paper could be of high interest to identify key features for the design of release-controlled nanomedicine for cancer treatment. Full article

(This article belongs to the Special Issue Advanced Functional Materials and 3D Printing for Tissue Engineering and Drug Delivery Applications)

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