From concept to in vivo testing: Microcontainers for oral drug delivery

Mazzoni, Chiara; Tentor, Fábio; Strindberg, Sophie; Nielsen, Line Hagner; Keller, Stephan Sylvest; Alstrøm, Tommy Sonne; Gundlach, Carsten; Müllertz, Anette; Marizza, Paolo

doi:10.1016/j.jconrel.2017.10.013

Cited by 55 publications

(108 citation statements)

References 46 publications

(62 reference statements)

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“…To fully protect the loaded cargo, the microcontainers can be sealed with a lid of e.g. a pH-sensitive polymer to facilitate release in certain regions of the GI tract 11,12,18,19 . More advanced designs have been proposed, where the microdevices are processed as two dimensional objects and then self-fold into container structures upon exposure to liquid 20 .…”

Section: Designmentioning

confidence: 99%

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Microfabricated devices for oral drug delivery

Nielsen

Keller

2018

Lab Chip

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Oral administration of drugs is most convenient for patients and therefore the ultimate goal when developing new medication. The physical barriers in the body, low pH of the stomach and degradation by enzymes in the gastrointestinal tract are a few of the obstacles to succeeding with oral drug delivery. Microfabricated devices show promise to overcome some of these hindrances and thereby improve the bioavailability of drugs after oral administration. There is an increasing focus on microfabricated oral drug delivery systems, and so far there have been three main groups of designs: patch-like structures, microcontainers and microwells. Here, we review the newest development in top-down microfabricated devices for oral drug delivery with coverage of the aspects of design, choice of material and fabrication techniques. Furthermore, the drug loading techniques and methods for testing are discussed. In addition, we discuss the future perspectives for microfabricated devices.

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Section: Designmentioning

confidence: 99%

“…Indeed, the transfer of drug across an intestinal epithelial cell monolayer has been seen to increase by a factor of ten using such microdevices 10 . Initial animal studies have also been published [10][11][12] showing an increase in oral bioavailability.…”

Section: Introductionmentioning

confidence: 99%

Microfabricated devices for oral drug delivery

Nielsen

Keller

2018

Lab Chip

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“…A lid of Eudragit ® L100 was deposited over the microcontainers as previously described [19], by spray coating an isopropanol solution with 1% w/v Eudragit ® L100 and 5% w/w (in relation to the polymer) dibutyl sebacate. Briefly, the solution was sprayed over the amoxicillin-loaded microcontainers one chip at a time using an ultrasonic spray coater (Exactacoat system, Sono-Tek, Milton, NY, USA) with an Accumist nozzle operating at 120 kHz.…”

Section: Loading Of Amoxicillin Into Microcontainers and Spray Coatinmentioning

confidence: 99%

“…The release of amoxicillin from the differently shaped microcontainers coated with Eudragit ® L100 was measured using a µDISS Profiler TM (Pion Inc., Billerica, MA, USA), as previously described in the literature [16,19,42]. Initially, a calibration curve was prepared by addition of different volumes of amoxicillin in PBS stock solution to 10 mL PBS (pH 7.4) followed by measurements of UV absorbance in the range of 270-280 nm.…”

Section: In Vitro Release Studiesmentioning

confidence: 99%

“…The concept of planar microdevices was further developed with the inclusion of nanostraw structures on the surface, which was shown to enhance bioadhesion in a Caco-2 cell flow system when compared to similar microdevices without nanostraws [18]. Microcontainers, one type of unidirectionally-releasing microdevice, have previously been shown to improve oral bioavailability of drugs and provide inherent mucoadhesion [16,19]. Microcontainers are micrometer-sized devices (fabricated in polymers) with an inner cavity for storage of the API.…”

Section: Introductionmentioning

confidence: 99%

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Cubic Microcontainers Improve In Situ Colonic Mucoadhesion and Absorption of Amoxicillin in Rats

Christfort

Guillot²,

Melero³

et al. 2020

Pharmaceutics

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An increased interest in colonic drug delivery has led to a higher focus on the design of delivery devices targeting this part of the gastrointestinal tract. Microcontainers have previously facilitated an increase in oral bioavailability of drugs. The surface texture and shape of microcontainers have proven to influence the mucoadhesion ex vivo. In the present work, these findings were further investigated using an in situ closed-loop perfusion technique in the rat colon, which allowed for simultaneous evaluation of mucoadhesion of the microcontainers as well as drug absorption. Cylindrical, triangular and cubic microcontainers, with the same exterior surface area, were evaluated based on in vitro release, in situ mucoadhesion and in situ absorption of amoxicillin. Additionally, the mucoadhesion of empty cylindrical microcontainers with and without pillars on the top surface was investigated. From the microscopy analysis of the colon sections after the in situ study, it was evident that a significantly higher percentage of cubic microcontainers than cylindrical microcontainers adhered to the intestinal mucus. Furthermore, the absorption rate constants and blood samples indicated that amoxicillin in cubic microcontainers was absorbed more readily than when cylindrical or triangular microcontainers were dosed. This could be due to a higher degree of mucoadhesion for these particular microcontainers.

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Microcontainer Delivery of Antibiotic Improves Treatment of Pseudomonas aeruginosa Biofilms

Birk

Haagensen

Johansen

et al. 2020

Adv Healthcare Materials

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Biofilm-associated infections are difficult to treat effectively with antibiotics despite repeated treatments. Polymeric microdevices (microcontainers) have previously been shown to engulf in mucus layers and to provide tunable release. Such devices may overcome the challenge of delivering antibiotics into the biofilm, increasing the local drug concentration and hence improve local bacterial killing. In this work, microcontainers are loaded with the antibiotic, ciprofloxacin hydrochloride, and functionalized with polymeric lids of polyethylene glycol (PEG), chitosan, or Eudragit S100. The PEG lid gives rise to a drug release comparable to uncoated microcontainers showing complete release after 8 h, whereas chitosan and Eudragit S100 lids result in continuous release during the course of 24 h. All antibiotic-containing microcontainers inhibit planktonic growth of Pseudomonas aeruginosa (PAO1) cells, but the degree of inhibition depends on the coating. Microcontainers with ciprofloxacin hydrochloride kill about three times more biofilm-associated PAO1 cells compared with a single standard bolus. Moreover, the use of microcontainers in biofilm result in bacterial killing equal to a constant flow of a three times higher concentration of solubilized antibiotics. These studies suggest that microcontainers can be useful for antibiotic delivery in treatment of biofilm-associated infections, resulting in more effective treatment and reduced use of antibiotics.

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From concept to in vivo testing: Microcontainers for oral drug delivery

Cited by 55 publications

References 46 publications

Microfabricated devices for oral drug delivery

Microfabricated devices for oral drug delivery

Cubic Microcontainers Improve In Situ Colonic Mucoadhesion and Absorption of Amoxicillin in Rats

Microcontainer Delivery of Antibiotic Improves Treatment of Pseudomonas aeruginosa Biofilms

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