A poly(ethylene glycol)-based surfactant for formulation of drug-loaded mucus penetrating particles

Abstract

Mucosal surfaces are protected by a highly viscoelastic and adhesive mucus layer that traps most foreign particles, including conventional drug and gene carriers. Trapped particles are eliminated on the order of seconds to hours by mucus clearance mechanisms, precluding sustained and targeted drug and nucleic acid delivery to mucosal tissues. We have previously shown that polymeric coatings that minimize adhesive interactions with mucus constituents lead to particles that rapidly penetrate human mucus secretions. Nevertheless, a particular challenge in formulating drug-loaded mucus penetrating particles (MPP) is that many commonly used surfactants are either mucoadhesive, or do not facilitate efficient drug encapsulation. We tested a novel surfactant molecule for particle formulation composed of Vitamin E conjugated to 5 kDa polyethylene glycol (VP5k). We show that VP5k-coated poly(lactide-co-glycolide) (PLGA) nanoparticles rapidly penetrate human cervicovaginal mucus, whereas PLGA nanoparticles coated with polyvinyl alcohol or Vitamin E conjugated to 1 kDa PEG were trapped. Importantly, VP5k facilitated high loading of paclitaxel, a frontline chemo drug, into PLGA MPP, with controlled release for at least 4 days and negligible burst release. Our results offer a promising new method for engineering biodegradable, drug-loaded MPP for sustained and targeted delivery of therapeutics at mucosal surfaces.

In Vivo Evaluation of Paclitaxel-Loaded Lipid Nanocapsules After Intravenous and Oral Administration on Resistant Tumor

“…This optimization increased by 3.7-and 11.7-fold Ptx bioavailability compared with standard LNCs and Ptx commercial formulation, respectively. It was demonstrated that the coating of particles with PEG increased diffusion through the mucus layer [48] if PEG had an optimal molecular weight [49] and if coating was dense enough [50]. These muco-penetrating particles used to promote oral absorption of drug, improve efficiently the bioavailability of Ptx [51].…”

Direct Determination of Chitosan–Mucin Interactions Using a Single-Molecule Strategy: Comparison to Alginate–Mucin Interactions

“…Added to this, mucus provides a substantial barrier to the diffusion of large, charged and lipophilic entities, which can dramatically reduce diffusion rates [87][88][89]. Indeed, these issues have resulted in increasing interest in the development of muco-inert carrier systems in the form of mucus-penetrating particles that avoid interaction with mucus and thus experience a lower diffusion barrier [84,[90][91][92][93].…”

Functional PLGA NPs for Oral Drug Delivery: Recent Strategies and Developments

“…A novel surfactant molecule for particle formulation composed of Vitamin E conjugated to 5 kDa poly(ethylene glycol) (VP5k) was used instead of Vitamin E conjugated to 1kDa PEG (Vitamin E-TPGS). VP5k-coated PLGA NPs rapidly penetrated human cervicovaginal mucus, whereas PLGA NPs coated with PVA or Vitamin TPGS were trapped [45].…”