Evaluation of Drug Delivery and Efficacy of Ciprofloxacin-Loaded Povidone Foils and Nanofiber Mats in a Wound-Infection Model Based on Ex Vivo Human Skin

Topical treatment of wound infections is often a challenge due to limited drug availability at the site of infection. Topical drug delivery is an attractive option for reducing systemic side effects, provided that a more selective and sustained local drug delivery is achieved. In this study, a poorly water-soluble antibiotic, ciprofloxacin, was loaded on polyvinylpyrrolidone (PVP)-based foils and nanofiber mats using acetic acid as a solubilizer. Drug delivery kinetics, local toxicity, and antimicrobial activity were tested on an ex vivo wound model based on full-thickness human skin. Wounds of 5 mm in diameter were created on 1.5 × 1.5 cm skin blocks and treated with the investigated materials. While nanofiber mats reached the highest amount of delivered drug after 6 h, foils rapidly achieved a maximum drug concentration and maintained it over 24 h. The treatment had no effect on the overall skin metabolic activity but influenced the wound healing process, as observed using histological analysis. Both delivery systems were efficient in preventing the growth of Pseudomonas aeruginosa biofilms in ex vivo human skin. Interestingly, foils loaded with 500 µg of ciprofloxacin accomplished the complete eradication of biofilm infections with 1 × 109 bacteria/wound. We conclude that antimicrobial-loaded resorbable PVP foils and nanofiber mats are promising delivery systems for the prevention or topical treatment of infected wounds.

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Polymer-Based Smart Drug Delivery Systems for Skin Application and Demonstration of Stimuli-Responsiveness

Polymers ◽

10.3390/polym13081285 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1285

Author(s):

Louise Van Gheluwe ◽

Igor Chourpa ◽

Coline Gaigne ◽

Emilie Munnier

Keyword(s):

Drug Delivery ◽

Drug Delivery Systems ◽

Ex Vivo ◽

Delivery Systems ◽

Stimuli Responsive ◽

Stimuli Responsive Polymers ◽

Smart Drug ◽

Smart Drug Delivery

Progress in recent years in the field of stimuli-responsive polymers, whose properties change depending on the intensity of a signal, permitted an increase in smart drug delivery systems (SDDS). SDDS have attracted the attention of the scientific community because they can help meet two current challenges of the pharmaceutical industry: targeted drug delivery and personalized medicine. Controlled release of the active ingredient can be achieved through various stimuli, among which are temperature, pH, redox potential or even enzymes. SDDS, hitherto explored mainly in oncology, are now developed in the fields of dermatology and cosmetics. They are mostly hydrogels or nanosystems, and the most-used stimuli are pH and temperature. This review offers an overview of polymer-based SDDS developed to trigger the release of active ingredients intended to treat skin conditions or pathologies. The methods used to attest to stimuli-responsiveness in vitro, ex vivo and in vivo are discussed.

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Enhanced Transdermal Delivery of Pranoprofen Using a Thermo-Reversible Hydrogel Loaded with Lipid Nanocarriers for the Treatment of Local Inflammation

Pharmaceuticals ◽

10.3390/ph15010022 ◽

2021 ◽

Vol 15 (1) ◽

pp. 22

Author(s):

María Rincón ◽

Marcelle Silva-Abreu ◽

Lupe Carolina Espinoza ◽

Lilian Sosa ◽

Ana Cristina Calpena ◽

...

Keyword(s):

Human Skin ◽

Topical Application ◽

Topical Treatment ◽

Transdermal Delivery ◽

Ex Vivo ◽

Skin Permeation ◽

In Vitro Release ◽

Heterogeneous Structure ◽

Clinical Environment ◽

Local Skin

A biocompatible topical thermo-reversible hydrogel containing Pranoprofen (PF)-loaded nanostructured lipid carriers (NLCs) was studied as an innovative strategy for the topical treatment of skin inflammatory diseases. The PF-NLCs-F127 hydrogel was characterized physiochemically and short-time stability tests were carried out over 60 days. In vitro release and ex vivo human skin permeation studies were carried out in Franz diffusion cells. In addition, a cytotoxicity assay was studied using the HaCat cell line and in vivo tolerance study was performed in humans by evaluating the biomechanical properties. The anti-inflammatory effect of the PF-NLCs-F127 was evaluated in adult male Sprague Daw-ley® rats using a model of inflammation induced by the topical application of xylol for 1 h. The developed PF-NLCs-F127 exhibited a heterogeneous structure with spherical PF-NLCs in the hydrogel. Furthermore, a thermo-reversible behaviour was determined with a gelling temperature of 32.5 °C, being close to human cutaneous temperature and thus favouring the retention of PF. Furthermore, in the ex vivo study, the amount of PF retained and detected in human skin was high and no systemic effects were observed. The hydrogel was found to be non-cytotoxic, showing cell viability of around 95%. The PF-NLCs-F127 is shown to be well tolerated and no signs of irritancy or alterations of the skin’s biophysical properties were detected. The topical application of PF-NLCs-F127 hydrogel was shown to be efficient in an inflammatory animal model, preventing the loss of stratum corneum and reducing the presence of leukocyte infiltration. The results from this study confirm that the developed hydrogel is a suitable drug delivery carrier for the transdermal delivery of PF, improving its dermal retention, opening the possibility of using it as a promising candidate and safer alternative to topical treatment for local skin inflammation and indicating that it could be useful in the clinical environment.

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Topical Drug Delivery to the Posterior Segment of the Eye

Pharmaceutics ◽

10.3390/pharmaceutics14010134 ◽

2022 ◽

Vol 14 (1) ◽

pp. 134

Author(s):

Marina Löscher ◽

Chiara Seiz ◽

José Hurst ◽

Sven Schnichels

Keyword(s):

Drug Delivery ◽

Animal Models ◽

Treatment Option ◽

Topical Treatment ◽

Delivery Systems ◽

Ocular Drug Delivery ◽

Posterior Segment ◽

Retinal Diseases ◽

Topical Drug Delivery ◽

Ocular Pharmacokinetics

Topical drug delivery to the posterior segment of the eye is a very complex challenge. However, topical delivery is highly desired, to achieve an easy-to-use treatment option for retinal diseases. In this review, we focus on the drug characteristics that are relevant to succeed in this challenge. An overview on the ocular barriers that need to be overcome and some relevant animal models to study ocular pharmacokinetics are given. Furthermore, a summary of substances that were able to reach the posterior segment after eye drop application is provided, as well as an outline of investigated delivery systems to improve ocular drug delivery. Some promising results of substances delivered to the retina suggest that topical treatment of retinal diseases might be possible in the future, which warrants further research.

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BioMEMS Technologies for Regenerative Medicine

MRS Proceedings ◽

10.1557/proc-1139-gg02-01 ◽

2008 ◽

Vol 1139 ◽

Cited By ~ 3

Author(s):

Jeffrey T. Borenstein

Keyword(s):

Drug Delivery ◽

Regenerative Medicine ◽

Drug Delivery Systems ◽

Ex Vivo ◽

Delivery Systems ◽

Organ Shortage ◽

Engineered Tissues ◽

Drug Concentrations

AbstractThe emergence of BioMEMS fabrication technologies such as soft lithography, micromolding and assembly of 3D structures, and biodegradable microfluidics, are already making significant contributions to the field of regenerative medicine. Over the past decade, BioMEMS have evolved from early silicon laboratory devices to polymer-based structures and even biodegradable constructs suitable for a range of ex vivo and in vivo applications. These systems are still in the early stages of development, but the long-term potential of the technology promises to enable breakthroughs in health care challenges ranging from the systemic toxicity of drugs to the organ shortage. Ex vivo systems for organ assist applications are emerging for the liver, kidney and lung, and the precision and scalability of BioMEMS fabrication techniques offer the promise of dramatic improvements in device performance and patient outcomes.Ultimately, the greatest benefit from BioMEMS technologies will be realized in applications for implantable devices and systems. Principal advantages include the extreme levels of achievable miniaturization, integration of multiple functions such as delivery, sensing and closed loop control, and the ability of precision microscale and nanoscale features to reproduce the cellular microenvironment to sustain long-term functionality of engineered tissues. Drug delivery systems based on BioMEMS technologies are enabling local, programmable control over drug concentrations and pharmacokinetics for a broad spectrum of conditions and target organs. BioMEMS fabrication methods are also being applied to the development of engineered tissues for applications such as wound healing, microvascular networks and bioartificial organs. Here we review recent progress in BioMEMS-based drug delivery systems, engineered tissue constructs and organ assist devices for a range of ex vivo and in vivo applications in regenerative medicine.

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Low molecular mass chitosan as carrier for a hydrodynamically balanced system for sustained delivery of ciprofloxacin hydrochloride

Acta Pharmaceutica ◽

10.2478/v10007-012-0013-2 ◽

2012 ◽

Vol 62 (2) ◽

pp. 237-250 ◽

Cited By ~ 14

Author(s):

Anurag Verma ◽

Ashok Bansal ◽

Amitava Ghosh ◽

Jayanta Pandit

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Molecular Mass ◽

Drug Delivery Systems ◽

Delivery Systems ◽

Water Soluble ◽

Sustained Delivery ◽

Ciprofloxacin Hydrochloride ◽

Water Soluble Drug ◽

Major Interest

Low molecular mass chitosan as carrier for a hydrodynamically balanced system for sustained delivery of ciprofloxacin hydrochloride Chitosan has become a focus of major interest in recent years due to its excellent biocompatibility, biodegradability and non-toxicity. Although this material has already been extensively investigated in the design of different types of drug delivery systems, it is still little explored for stomach specific drug delivery systems. The objective of the present investigation was to explore the potential of low molecular mass chitosan (LMCH) as carrier for a hydrodynamically balanced system (HBS) for sustained delivery of water soluble drug ciprofloxacin hydrochloride (CP). Various formulations were prepared by physical blending of drug and polymer(s) in varying ratios followed by encapsulation into hard gelatin capsules. All the formulations remained buoyant in 0.1 mol L-1 HCl (pH 1.2) throughout the experiment. Effect of addition of xanthan gum (XG) or ethyl cellulose (EC) on drug release was also investigated. Zero order drug release was obtained from the formulations containing LMCH alone or in combination with XG, and in one instance also with EC. Our results suggest that LMCH alone or in combination with XG is an excellent material for stomach specific sustained delivery of CP from hydrodynamically balanced single unit capsules.

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Should local drug delivery systems be used in dentistry?

Drug Delivery and Translational Research ◽

10.1007/s13346-021-01053-x ◽

2021 ◽

Author(s):

Joana Vieira Costa ◽

Jaime Portugal ◽

Cristina Bettencourt Neves ◽

Ana F. Bettencourt

Keyword(s):

Drug Delivery ◽

Drug Delivery Systems ◽

Delivery Systems ◽

Local Drug Delivery

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Innovative Strategies for Lipid-Based Drug Delivery

Multifunctional Nanocarriers for Contemporary Healthcare Applications - Advances in Medical Technologies and Clinical Practice ◽

10.4018/978-1-5225-4781-5.ch004 ◽

2018 ◽

pp. 60-84 ◽

Cited By ~ 1

Author(s):

Navneet Sharma ◽

Sabna Kotta ◽

Mohd Aleem ◽

Shubham Singh ◽

Rakesh Kumar Sharma

Keyword(s):

Drug Delivery ◽

Drug Absorption ◽

Drug Delivery Systems ◽

Delivery Systems ◽

Water Soluble ◽

Absorption Process ◽

Innovative Strategies ◽

The Poor ◽

Water Soluble Drugs ◽

Selection Of

In the last decade, there has been a mounting concern in lipid-based formulations to deliver water-soluble drugs. Lipid-based drug delivery systems are one of the budding and promising technologies designed to tackle the poor bioavailability problems. This chapter stresses the different mechanisms of lipophilic drug absorption along with its advantages and limitations. It points out the different mechanisms of how lipid-based excipients and the different formulations interact with the absorption process. This review provides a comprehensive summary about the lipid formulation classification scheme (LFCS), a guide for the selection of appropriate formulation and commonly used excipients for lipid-based formulations, along with the important factors to be considered in formulation design and excipient selection. This review also focuses on the formulation of solid lipid-based formulations, important evaluation aspects, and commercial formulations available for the purpose.

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SCIDOT-18. NANOTHERAPEUTICS FOR NEUROSURGICALLY-APPLIED DRUG DELIVERY

Neuro-Oncology ◽

10.1093/neuonc/noz175.1154 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi275-vi275

Author(s):

Catherine Vasey ◽

Vincenzo Taresco ◽

Stuart Smith ◽

Cameron Alexander ◽

Ruman Rahman

Keyword(s):

Drug Delivery ◽

Ex Vivo ◽

Drug Formulation ◽

Local Drug Delivery ◽

Resection Margins ◽

Therapeutic Drug ◽

Tumour Resection ◽

Combination Drug ◽

Drug Encapsulation ◽

Drug Concentrations

Abstract Design and implementation of innovative local drug delivery systems (DDS) may overcome current limitations in GBM treatment, such as the lack of therapeutic drug concentrations reaching residual GBM cells following surgery. Here we describe a novel DDS which utilises a bespoke mechanically engineered spray device, designed for safe surgical use, to deliver a mucoadhesive hydrogel containing chemotherapeutic nanoparticles (NPs) into the tumour resection margins. The overall aim is to spray a NP and polymer solution onto the resection cavity and potentially increase penetration of anti-cancer drugs within the 2 cm reoccurrence zone beyond the infiltrative margin. The mucoadhesive gel of choice, pectin, is currently used in other in vivo applications; however we have repurposed this for the brain. Pectin is biocompatible with GBM and human astrocyte cells in vitro and showed neither toxicity nor inflammation for up to 2 weeks upon orthotopic brain injection. Pectin is biodegradable in artificial CSF and is capable of being sprayed from the engineered device. A panel of polymeric, oil-based and polymer-coated NPs have been developed and optimised to maximise drug encapsulation of etoposide and olaparib as proof-of-concept for combination drug delivery. Etoposide/olaparib was chosen due to cytotoxicity from 5 GBM cell lines, including primary lines isolated from the invasive tumour margin (Mean IC50 of 1.1 µM and 8.3 µM respectively). The optimal NP/drug formulation (based on drug encapsulation, spray capability and bio-adhesiveness) will ultimately be assessed for tolerability and efficacy using orthotopic allograft and xenograft high-grade glioma models, including measurement of penetration of drug/nanoparticle in ex vivo murine and porcine brain using novel hybrid time-of-flight/Orbitrap TM secondary ion mass spectrometer (orbiSIMS) technology.

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