Optimization of prednisolone-loaded long-circulating liposomes via application of Quality by Design (QbD) approach

Abstract

Quality by design principles (QbD) were used to assist the formulation of prednisolone-loaded long-circulating liposomes (LCL-PLP) in order to gain a more comprehensive understanding of the preparation process. This approach enables us to improve the final product quality in terms of liposomal drug concentration, encapsulation efficiency and size, and to minimize preparation variability. A 19-run D-optimal experimental design was used to study the impact of the highest risk factors on PLP liposomal concentration (Y- μg/ml), encapsulation efficiency (Y-%) and size (Y-nm). Out of six investigated factors, four of them were identified as critical parameters affecting the studied responses. PLP molar concentration and the molar ratio of DPPC to MPEG-2000-DSPE had a positive impact on both Y and Y, while the rotation speed at the formation of the lipid film had a negative impact. Y was highly influenced by prednisolone molar concentration and extrusion temperature. The accuracy and robustness of the model was further on confirmed. The developed model was used to optimize the formulation of LCL-PLP for efficient accumulation of the drug to tumor tissue. The cytotoxicity of the optimized LCL-PLP on C26 murine colon carcinoma cells was assessed. LCL-PLP exerted significant anti-angiogenic and anti-inflammatory effects on M2 macrophages, affecting indirectly the C26 colon carcinoma cell proliferation and development.

Pharmaceutical Development of Liposomes Using the QbD Approach

“…The most important element in using QbD concept to assist formulation and process design is to predefine the desired final product quality profile [9,14,20].…”

“…It involves designing a formulation and manufacturing process in such a way to obtain a pharmaceutical product with predetermined quality specifications [12]. QbD identifies characteristics that are critical to quality of the product, translates them into attributes that the drug should possess, and establishes how the critical formulation and process parameters can be varied to constantly produce a drug product with the desired characteristics [13,14]. The goal of the QbD approach is in-depth understanding of the formulation and process variables, and of the relationship between them, in order to obtain a drug product with consistent desired characteristics [15,16].…”

The Effect of Nano-Epigallocatechin-Gallate on Oxidative Stress and Matrix Metalloproteinases in Experimental Diabetes Mellitus

“…For the preparation of liposomes, we used a modified film hydration method [44,45]. The lipid double-layer components, having a 70 mM concentration (DPPC:MPEG-2000-DSPE:CHO = 4.75:0.25:1 molar ratio), were dissolved in ethanol in a round-bottomed glass flask.…”

Targeted Based Drug Delivery System for Colon Cancer

“…The LCL encapsulated 5-FU (LCL-5-FU) can also help in reducing the drug toxicity on healthy tissues. The combination of LCL-5-FU with LCL containing PLP (LCL-PLP) has inhibitory effects in colon carcinoma in vivo [69] caused by tumor angiogenesis suppression [70] and can help in the improvement of CRC treatment. To compare the antitumor activity of combined liposomal drug therapy based on simultaneous administration of 20 mg/kg LCL-PLP and 1.2 mg/kg LCL-5-FU with that induced by liposomal monotherapy (either 20 mg/kg LCL-PLP or 1.2 mg/kg LCL-5-FU) on the growth of C26 colon carcinoma in vivo, mice were injected i.v.…”