Evidence map›Paper›PMID 26508478›Full record

ArticlePharmaceutical research2016

Sustained Pulmonary Delivery of a Water-Soluble Antibiotic Without Encapsulating Carriers.

Winston Ong, Pawel Nowak, Yen Cu, Lisa Schopf, James Bourassa, Elizabeth Enlow, Samuel M Moskowitz, Hongming Chen

Abstract read
In one paragraph

Article in Pharmaceutical research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.5field-weighted citation impact, top 31% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Article
  3. Mucus-Penetrating Particles and the Role of Ocular Mucus as a Barrier to Micro- and Nanosuspensions.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Winston OngKala Pharmaceuticals, Inc., 100 Beaver Street, Suite 201, Waltham, Massachusetts, 02453, USA. winston.ong@kalarx.com.
Pawel NowakKala Pharmaceuticals, Inc., 100 Beaver Street, Suite 201, Waltham, Massachusetts, 02453, USA.
Yen CuKala Pharmaceuticals, Inc., 100 Beaver Street, Suite 201, Waltham, Massachusetts, 02453, USA.
Lisa SchopfKala Pharmaceuticals, Inc., 100 Beaver Street, Suite 201, Waltham, Massachusetts, 02453, USA.
James BourassaKala Pharmaceuticals, Inc., 100 Beaver Street, Suite 201, Waltham, Massachusetts, 02453, USA.
Elizabeth EnlowKala Pharmaceuticals, Inc., 100 Beaver Street, Suite 201, Waltham, Massachusetts, 02453, USA.
Samuel M MoskowitzDepartment of Pediatrics, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, 02114, USA.
Hongming ChenKala Pharmaceuticals, Inc., 100 Beaver Street, Suite 201, Waltham, Massachusetts, 02453, USA.
Kala Pharmaceuticals (United States) · USMassachusetts General Hospital · US

Funding

Mucus-Penetrating Antibiotics for Lung Infections Associated with Cystic FibrosisR43HL106899 · NHLBI · KALA PHARMACEUTICALS, INC. · PI CHEN, HONGMING · 2011 to 2011
$180k
NHLBI NIH HHS R43 HL106899NHLBI NIH HHS R43HL106899
6 · The paper itself

Abstract

purposeTraditional polymeric nanoparticle formulations for prolonged local action during inhalation therapy are highly susceptible to muco-ciliary clearance. In addition, polymeric carriers are typically administered in high doses due to finite drug loading. For toxicological reasons, these carriers and their degradation byproducts are undesirable for inhalation therapy, particularly for chronic use, due to potential lung accumulation.

methodsWe synthesized a novel, insoluble prodrug (MRPD) of a time-dependent β-lactam, meropenem, and formulated MRPD into mucus-penetrating crystals (MRPD-MPCs). After characterizing their mucus mobility (in vitro) and stability, we evaluated the lung pharmacokinetics of intratracheally-instilled MRPD-MPCs and a meropenem solution in guinea pigs.

resultsMeropenem levels rapidly declined in the lungs of guinea pigs receiving meropenem solution compared to those given MRPD-MPCs. At 9 h after dosing, drug levels in the lungs of animals that received meropenem solution dropped to 12 ng/mL, whereas those that received MRPD-MPCs maintained an average drug level of ≥1,065 ng/mL over a 12-h period.

conclusionsThis work demonstrated that the combination of prodrug chemistry and mucus-penetrating platform created nanoparticles that produced sustained levels of meropenem in guinea pig lungs. This strategy represents a novel approach for sustained local drug delivery to the lung without using encapsulating matrices.

Indexed as

AnimalsAnti-Bacterial AgentsChemistry, PharmaceuticalDelayed-Action PreparationsDrug CarriersDrug Delivery SystemsGuinea PigsHumansLungMaleMeropenemMucusProdrugsSolubilitySolutionsThienamycinsAnti-Bacterial AgentsDelayed-Action PreparationsDrug CarriersMeropenemProdrugsSolutionsThienamycinsWaterantibioticsdrug deliverymeropenemmucusnanoparticleprodrug

Identifiers

PMID26508478
PMCPMC4744570
OpenAlexW1886051950

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.