Controlled-release nanoencapsulating microcapsules to combat inflammatory diseases

Drug Des Devel Ther. 2017 Jun 8:11:1707-1717. doi: 10.2147/DDDT.S133344. eCollection 2017.

Abstract

The World Health Organization (WHO) has reported that globally 235 million people suffer from chronic and other inflammatory diseases. The short half-lives of nonsteroidal anti-inflammatory drugs (NSAIDs) and their notoriety in causing gastrointestinal discomforts, warrants these drugs to be released in a controlled and sustained manner. Although polymeric particles have been widely used for drug delivery, there are few reports that showcase their ability in encapsulating and sustaining the release of NSAIDs. In this paper, polymeric nanoencapsulating microcapsules loaded with NSAIDs were fabricated using solid/water/oil/water emulsion solvent evaporation method. Two NSAIDs, ibuprofen and naproxen, were first pre-loaded into nanoparticles and then encapsulated into a larger hollow microcapsule that contained the third NSAID, celecoxib. A high encapsulation efficiency (%) of these NSAIDs was achieved and a sustained release (up to 30 days) of these drugs in phosphate-buffered saline was observed. Then, a gastrointestinal drug - cimetidine (CIM) - was co-loaded with the NSAIDs. This floating delivery system exhibited excellent buoyancy (~88% up to 24 h) in simulated gastric fluid. It also allowed a sequential release of the drugs, whereby an immediate release of CIM followed by NSAIDs was observed. Drug release of the NSAIDs observed Fickian diffusion mechanism, whereas CIM observed non-Fickian diffusion. Therefore, this delivery system is a promising platform to control the delivery of NSAIDs to combat inflammatory diseases, thereby protecting against possible gastrointestinal side effects that may arise from the overuse of NSAIDs.

Keywords: NSAIDs; diffusion; emulsion; floating oral drug delivery; injectable system; multi-drug encapsulation; oral delivery systems; sequential release; sustained release.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / chemistry*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Capsules
  • Celecoxib / chemistry*
  • Celecoxib / therapeutic use
  • Cimetidine / chemistry
  • Delayed-Action Preparations
  • Diffusion
  • Drug Combinations
  • Drug Compounding
  • Drug Liberation
  • Drug Stability
  • Gastric Juice / chemistry
  • Histamine H2 Antagonists / chemistry
  • Ibuprofen / chemistry*
  • Ibuprofen / therapeutic use
  • Inflammation / prevention & control*
  • Kinetics
  • Models, Chemical
  • Nanocapsules*
  • Nanotechnology*
  • Naproxen / chemistry*
  • Naproxen / therapeutic use
  • Polymers / chemistry
  • Solubility
  • Technology, Pharmaceutical / methods*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Capsules
  • Delayed-Action Preparations
  • Drug Combinations
  • Histamine H2 Antagonists
  • Nanocapsules
  • Polymers
  • Naproxen
  • Cimetidine
  • Celecoxib
  • Ibuprofen