Solid lipid micro-dispersions (SLMs) based on PEGylated solidified reverse micellar solutions (SRMS): a novel carrier system for gentamicin.
The purpose of this study was to formulate and evaluate novel PEGylated solidified reverse micellar solutions (SRMS)-based solid lipid microparticles (SLMs) for improved delivery of gentamicin. Lipid matrix (SRMS) [consisting of 15% w/w Phospholipon® 90G (P90G) in 35% w/w dika wax (Irvingia gabonensis) was formulated and characterized by differential scanning calorimetry (DSC). SLMs were formulated by melt-emulsification using the SRMS, PEG 4000 and gentamicin (1.0, 2.0, 3.0% w/w), and their physicochemical as well as pharmacokinetic parameters determined. In vitro permeation of gentamicin from the SLMs through artificial membrane (0.22 μm pore size) was carried out using Franz's cell and phosphate-buffered saline (PBS, pH 7.4) as acceptor medium, while bioevaluation was performed using clinical isolates of Pseudomonas aeruginosa and Staphylococcus aureus. Stable and irregularly-shaped gentamicin-loaded SLMs of size range 34.49 ± 2.56 to 53.52 ± 3.09 µm were obtained. The SLMs showed sustained drug permeation and exhibited time-dependent and capacity-limited bioactivity. Overall, SLMs containing 2% w/w SRMS, 3% w/w gentamicin and PEG 4000 entrapped the highest amount of drug, gave highest IZD against the test organisms and highest permeation flux (5.239 μg/cm(2).min) and permeation coefficient (1.781 × 10(-6)cm/min) within 420 min, while pure gentamicin gave the least. Preliminary in vivo pharmacokinetic studies also showed an AUC-24 of 1507 µg/h/ml for the optimized formulation, while that of oral drug solution was 678 µg/h/ml. This showed a 2.2-fold increase in the systemic bioavailability of gentamicin from the optimized formulation. PEGylated SRMS-based SLMs prepared with heterolipid from Irvingia gabonensis would likely offer a reliable delivery system for gentamicin.
a Department of Pharmaceutics , University of Nigeria , Nsukka , Enugu State , Nigeria.
Franklin C
FC
Kenechukwu
a Department of Pharmaceutics , University of Nigeria , Nsukka , Enugu State , Nigeria.
Mumuni A
MA
Momoh
a Department of Pharmaceutics , University of Nigeria , Nsukka , Enugu State , Nigeria.
Petra O
PO
Nnamani
a Department of Pharmaceutics , University of Nigeria , Nsukka , Enugu State , Nigeria.
Anthony A
AA
Attama
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001431:Bacteriological Techniques; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D005839:Gentamicins / Q000008:administration & dosage* / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008823:Micelles; D010316:Particle Size; D010539:Permeability; D010713:Phosphatidylcholines / Q000737:chemistry; D010938:Plant Oils / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013211:Staphylococcus aureus / Q000187:drug effects
D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D005839:Gentamicins; D008823:Micelles; D010713:Phosphatidylcholines; D010938:Plant Oils; C023475:dika fat; C585968:phospholipon 90G; D011092:Polyethylene Glycols; C000595214:polyethylene glycol 4000
Dika wax (Irvingia gabonensis); PEGylation; gentamicin; lipid-based drug delivery system; solid lipid microparticles