title: Highly water-soluble mast cell stabiliser-encapsulated solid lipid nanoparticles with enhanced oral bioavailability.
abstract: Cromolyn sodium (CS), a mast cell stabiliser, is widely employed for the prevention and treatment of allergic conditions. However, high hydrophilicity and poor oral permeability hinder its oral clinical translation. Here, solid lipid nanoparticles (SLNs) have been developed for the purpose of oral bioavailability enhancement. The CS-SLNs were engineered by double emulsification method (W1/O/W2) and optimised by using Box-Behnken experimental design. The surface and solid-state characterisations revealed the presence of CS in an amorphous form without any interactions inside the spherical-shaped SLNs. The in-vitro release study showed an extended release up to 24 hr by diffusion controlled process. Ex-vivo and in-vivo intestinal permeation study showed ∼2.96-fold increase in permeability of CS by presentation as SLNs (p < 0.05). Further, in-vivo pharmacokinetic study exhibited ∼2.86-fold enhancements in oral bioavailability of CS by encapsulating inside SLNs, which clearly indicate that SLNs can serve as the potential therapeutic carrier system for oral delivery of CS.
authors.affiliation: a Department of Pharmaceutics , Indian Institute of Technology (Banaras Hindu University) , Varanasi , India.
authors.forename: Ravi R
authors.initials: RR
authors.lastname: Patel
authors.affiliation: a Department of Pharmaceutics , Indian Institute of Technology (Banaras Hindu University) , Varanasi , India.
authors.forename: Sundeep
authors.initials: S
authors.lastname: Chaurasia
authors.affiliation: a Department of Pharmaceutics , Indian Institute of Technology (Banaras Hindu University) , Varanasi , India.
authors.forename: Gayasuddin
authors.initials: G
authors.lastname: Khan
authors.affiliation: a Department of Pharmaceutics , Indian Institute of Technology (Banaras Hindu University) , Varanasi , India.
authors.forename: Pramila
authors.initials: P
authors.lastname: Chaubey
authors.affiliation: a Department of Pharmaceutics , Indian Institute of Technology (Banaras Hindu University) , Varanasi , India.
authors.forename: Nagendra
authors.initials: N
authors.lastname: Kumar
authors.affiliation: a Department of Pharmaceutics , Indian Institute of Technology (Banaras Hindu University) , Varanasi , India.
authors.forename: Brahmeshwar
authors.initials: B
authors.lastname: Mishra
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D004205:Cromolyn Sodium / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D057927:Hydrophobic and Hydrophilic Interactions; D007408:Intestinal Absorption; D008055:Lipids / Q000737:chemistry*; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry*; D051381:Rats; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D018927:Anti-Asthmatic Agents; D004337:Drug Carriers; D008055:Lipids; D014867:Water; D004205:Cromolyn Sodium
keywords: Box–Behnken experimental design; Cromolyn sodium; intestinal permeability; oral bioavailability; solid lipid nanoparticles