Solid lipid micro-dispersions (SLMs) based on PEGylated solidified reverse micellar solutions (SRMS): a novel carrier system for gentamicin

Abstract

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.

Novel Intravaginal Drug Delivery System Based on Molecularly PEGylated Lipid Matrices for Improved Antifungal Activity of Miconazole Nitrate

“…However, all PEGylated adducts of LM (1:6) had lower melting peaks with corresponding higher enthalpies than non-PEGylated LM 1:6 Also, increased amount of PEG 4000 led to a slight increase in the melting point, while the enthalpies initially decreased and then increased slightly with increased PEG 4000 content. PEG-LM (1:9) showed the greatest enhancement in the disorderliness of the lipid matrices, which would result to increased drug incorporation and holding capacity of the LM (1:9), consistent with previous reports [ 38 , 48 ]. In addition, the DSC thermograms of LM (1:9) and its PEGylated adducts are the most consistent in terms of the melting temperature range; they melted over the greatest (widest) temperature range (25–75°C).…”

“…This valuable information is necessary to establish the possibility of modifying the properties of polymers and lipids and also to confirm the stability of drugs in polymeric or lipidic systems [ 23 , 36 , 38 ]. Since higher melting point or enthalpy values indicate more ordered crystal structures [ 38 ], it follows that the interaction between the fatty acid contents of SO (which is a super-refined unsaturated oil from sunflower) and Softisan® 154 (super-saturated hydrogenated palm oil) resulted in the partly disordered crystalline arrangement which suggests great deformation in the lattice structure [ 38 ]. Higher amount of the liquid lipid (SO) in the LM gave rise to a relatively amorphous structure as shown by the lower melting peak of LM (1:1) compared to other LMs.…”

“…The practical yields of the SLMs dispersions from each lipid matrix were determined to evaluate the efficiency of the method of preparation by measuring their weights. The percentage (%) yield was calculated using [ 38 ] where W 1 is the weight of the SLMs formulated (g), W 2 is the weight of the drug added (g), and W 3 is the weight of the lipid and other excipients (g).…”

“…The pH and particle size of the SLMs from each batch were determined in a time-dependent manner after one week, one month, and three months of storage at room temperature [ 38 ].…”

“…This may be especially important for treating pregnant patients suffering from VVC. Previous study by our research group demonstrated that PEGylated solid lipid microdispersions of gentamicin (an aminoglycoside antibiotic) were quite useful for skin targeting via topical route and notably offered localized antibacterial effect [ 38 ]. Consequently, exploring the potential of tailor-made drug delivery carriers such as lipid-based PEGylated delivery system in improving the topical vaginal delivery of antifungal drugs such as MN for localized treatment of VVC seems worthwhile.…”