Dexamethasone Loaded Liposomes by Thin-Film Hydration and Microfluidic Procedures: Formulation Challenges

Abstract

Liposomes have been one of the most exploited drug delivery systems in recent decades. However, their large-scale production with low batch-to-batch differences is a challenge for industry, which ultimately delays the clinical translation of new products. We have investigated the effects of formulation parameters on the colloidal and biopharmaceutical properties of liposomes generated with a thin-film hydration approach and microfluidic procedure. Dexamethasone hemisuccinate was remotely loaded into liposomes using a calcium acetate gradient. The liposomes produced by microfluidic techniques showed a unilamellar structure, while the liposomes produced by thin-film hydration were multilamellar. Under the same remote loading conditions, a higher loading capacity and efficiency were observed for the liposomes obtained by microfluidics, with low batch-to-batch differences. Both formulations released the drug for almost one month with the liposomes prepared by microfluidics showing a slightly higher drug release in the first two days. This behavior was ascribed to the different structure of the two liposome formulations. In vitro studies showed that both formulations are non-toxic, associate to human Adult Retinal Pigment Epithelial cell line-19 (ARPE-19) cells, and efficiently reduce inflammation, with the liposomes obtained by the microfluidic technique slightly outperforming. The results demonstrated that the microfluidic technique offers advantages to generate liposomal formulations for drug-controlled release with an enhanced biopharmaceutical profile and with scalability.

Dexamethasone-Loaded Lipomers: Development, Characterization, and Skin Biodistribution Studies

“…Thus, formulation LP03 was selected as the final formulation, with lower levels of both surfactants (1.5% w / w of Tween 80 and 0.16% w / w of Span 60). The %LC of batch LP03 was calculated following Equation (2), which resulted in 30.22%, thus confirming the high loading capacity of this type of nanoencapsulation system [ 5 ] compared to other drug delivery systems like liposomes, in which Amin et al reached an LC of 12.6% [ 16 ].…”

“…Lipomers are a promising drug delivery system to improve the therapeutical balance of DEX in AA treatment, due to possible accumulation in the pilosebaceous unit, where the disease takes place, and under the hypothesis that the lipid nucleus increases the loading capacity. This fact leads to a higher drug concentration in the LPNCs, compared with similar particles without the lipidic core, for which the DEX loading capacity was about 1–2% [ 16 ].…”

TPGS-Modified Long-Circulating Liposomes Loading Ziyuglycoside I for Enhanced Therapy of Myelosuppression

“…Over the past few decades, different approaches have been proposed to manufacture liposomes. 22 These include lipid film hydration, reverse phase evaporation, ethanol injection, ether injection, detergent removal, etc. Such methods are simple, rapid, and energy- and cost-efficient, ideal for laboratory-scale production and synthesis of smaller particle sizes with narrow particle size distribution.…”

Evaluation of Drug-Loading Ability of Poly(Lactic Acid)/Hydroxyapatite Core–Shell Particles

“…Li et al reported that polymeric micelles with π–π conjugated moieties as lipophilic segments for delivering anticancer agents exhibited an LC value of 15% [ 23 ]. Al-Amin et al reported liposome particles with an LC value of 12% [ 44 ]. Therefore, PLHA-V x exhibited an excellent drug-loading capacity, with an LC value of 250%.…”