Amphotericin B liposomal formulation: applicable preparation methods, challenges, and tips.

OBJECTIVE: This study was intended to explore and evaluate the appropriate methods for preparation of Amphotericin B (AmB) liposomes with acceptable characteristics. SIGNIFICANCE: This project provides pre-formulations for industrial manufacturing of liposomal AmB which confers improved properties, besides reduced toxicity compared with the plain drug. METHODS: At first, Solubility screening tests were performed, and in the following, three liposome preparation methods including ethanol injection, solvent evaporation, and solvent-free method were examined. In the following, the physicochemical characteristics of the prepared liposomes as well as size, size distribution, zeta potential (ZP), morphology, drug loading, loading capacity, physicochemical stability, and drug-lipid interaction studies were investigated. HPLC was applied for analyzing AmB. RESULTS: In all three methods, liposomes with acceptable characteristics were obtained. The size range of liposomes was 150.3 to 263.9 nm and polydispersity index ≤0.32. In morphologic evaluations, the liposomes have appeared as spherical and separate vesicles. A physical loading of AmB without specific interaction between components was achieved. The lyophilized powder in the solvent-free method was physicochemically stable for 6 months without changes in appearance; the remaining drug after 6-month storage at 25 °C and 60% RH, accounts for 91.5 ± 0.5% compared with the initial drug loaded in liposomes, and degradation pattern follows a linear order. CONCLUSION: As a result, AmB-loaded liposomes were prepared in three applicable methods. The solvent-free method can be considered the most economical and environmental-friendly.

Surface modification with cholesteryl acetyl carnitine, a novel cationic agent, elevates cancer cell uptake of the PEGylated liposomes.

The present study aimed to synthesize cholesteryl acetyl carnitine (CAC), and surface modify the PEGylated liposomes with the intention of enhanced cancer cell uptake. For this, CAC synthesis was performed in amine-free esterification conditions and then four liposomal formulations of unmodified, CAC/PEG, and CAC + PEG-modified were prepared by ethanol injection method. Cytotoxicity of the liposomes was investigated in A549 cells, followed by cellular uptake assessments of coumarin 6 (C6)-loaded liposomes. The results of ATR-FTIR, 1HNMR, and 13CNMR demonstrated successful formation of CAC. A molecular docking study showed efficient binding affinities rather than carnitine to the active site of four carnitine transporters. Liposomal formulations possessed spherical morphology with a mean particle size range of 112-138 nm, narrow size distribution, and negative surface charge. All formulations had low cytotoxicity at 0.5 mg/ml, but high cytotoxicity at around 2.5 mg/ml. The lowest IC50 was obtained for CAC modified liposomes. CAC + PEG-modified liposomes had the highest cellular uptake. In conclusion, CAC + PEG modification of liposomes is an effective approach for increasing A549 cellular uptake, with low cytotoxicity at commonly applied liposome concentrations. The elevated uptake may be due to the involvement of the organic cation transporter, cationic structure, and the metabolic preference of CAC in cancer cells.

The latest advances of cisplatin liposomal formulations: essentials for preparation and analysis.

Introduction: Cisplatin has been indicated for several malignancies all over the world for many years. Increasing patient tolerance for high dose of chemotherapeutics and reducing side effects has been granted by drug encapsulated liposomal systems. There have been much efforts for improving cisplatin delivery to the site of action via liposomes both in research and clinical trials such as SPI-077®, Liplacis®, and Lipoplatin®.Areas covered: In this review, we have discussed about cisplatin and its liposomal formulations, focusing on different preparation methods and analysis approaches such as atomic absorption, mass spectroscopy, UV, electrochemical methods, and emphasizing on HPLC as one of the accurate and specific methods for determination of cisplatin species and also measurement of total platinum by derivation.Expert opinion: Liposome of cisplatin has offered potential beneficial aspects over cisplatin formulation. However, there are several challenges in preparing and analysis of cisplatin liposomes due to cisplatin's great reactivity, formation of several species, high affinity to bioelements, insufficient release at the tumor site, and inefficient loading. Cisplatin resistance is another challenge which should be prevented by higher loading capacity. Charge-dependent interactions should also be highly considered especially in the preparation step.

Liposome and immune system interplay: Challenges and potentials.

Liposome as a revolutionizing carrier, has exhibited favorable aspects in drug delivery. However, there are numerous challenges affecting its effectiveness. Hypersensitivity, accelerated blood clearance, opsonization, uptake by reticulo-endothelial system, and also immune suppression are known as the dominant manifestations of immune-related effects. They may cause failure to achieve the proof of regulatory approvals. In this review, liposome challenges in biologic environment have been discussed. Moreover, opsonization and liposome interactions with innate and acquired immune system have been investigated. Immune system elements including the corresponding receptors and cells were reviewed in this regard. By exploring immune related interactions of the liposome, it could be possible for the formulators to be aware of the immune related interactions of the administered liposomal formulation. On the other hand, immune targeted liposomes for immunotherapy and vaccination purposes could also be developed.