Formulation Optimization of Freeze-Dried Long-Circulating Liposomes and In-Line Monitoring of the Freeze-Drying Process Using an NIR Spectroscopy Tool

Sylvester, Bianca; Porfire, Alina; Bockstal, Pieter-Jan Van; Porav, Sebastian; Achim, Marcela; Beer, Thomas De; Tomuță, Ioan

doi:10.1016/j.xphs.2017.05.024

Cited by 42 publications

(27 citation statements)

References 53 publications

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“…Only recently, the use of Raman and near-infrared (NIR) spectroscopy was proposed as a complementary tool of Pirani measurements to supply the information about the acyl chain packing of the liposome bilayers and predict if any harmful events would occur. This approach would allow, giving a better understanding of the process, to improve process efficiency by optimizing the primary and secondary drying time [ 50 ].…”

Section: Stresses Of Liposomal Dispersions Occurring During Freezementioning

confidence: 99%

Lyophilization of Liposomal Formulations: Still Necessary, Still Challenging

et al. 2018

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Nowadays, the freeze-drying of liposome dispersions is still necessary to provide a solid dosage form intended for different routes of administration (i.e., parenteral, oral, nasal and/or pulmonary). However, after decades of studies the optimization of process conditions remains still challenging since the freezing and the dehydration destabilize the vesicle organization with the concomitant drug leakage. Starting from the thermal properties of phospholipids, this work reviews the main formulation and process parameters which can guarantee a product with suitable characteristics and increase the efficiency of the manufacturing process. In particular, an overview of the cryo- and/or lyo-protective mechanisms of several excipients and the possible use of co-solvent mixtures is provided. Attention is also focused on the imaging methods recently proposed to characterize the appearance of freeze-dried products and liposome dispersions upon reconstitution. The combination of such data would allow a better knowledge of the factors causing inter-vials variability in the attempt to improve the quality of the final medicinal product.

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Section: Stresses Of Liposomal Dispersions Occurring During Freezementioning

confidence: 99%

Lyophilization of Liposomal Formulations: Still Necessary, Still Challenging

et al. 2018

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“…Values represent the mean + SD of 2 independent experiments. Significant differences between liposomes without and with saccharides were detected as shown by an *P < 0.05 and **P < 0.005. have a water content <2% (Sylvester et al, 2018). The total amount of residual water in liposomes after freeze-drying was herein determined by TGA.…”

Section: Residual Water Contentmentioning

confidence: 99%

“…The inclusion of cryo and lyoprotectants in the liposomal formulation has been undertaken to improve the functional properties and stability of the products after freezing and drying, respectively (Costantino et al, 2004). Since they show the ability to act as the integrity membrane protectants, carbohydrates, more specific the saccharides, are the preferable cryo/lyoprotectants used during dehydration/rehydration of liposomes (Hua et al, 2003;Sylvester et al, 2018). To achieve a highly stable liposomal formulation some aspects must be optimized, namely the type and concentration of saccharide.…”

Section: Introductionmentioning

confidence: 99%

Protective Effect of Saccharides on Freeze-Dried Liposomes Encapsulating Drugs

Guimarães

Noro

Silva

et al. 2019

Front. Bioeng. Biotechnol.

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The production of freeze-dried liposomes encapsulating drugs is considered a key challenge since the drugs are prone to leakage. The aim of this work was to study the effect of different saccharides on preserving the stability and drug retention capacity of a previously developed liposomal formulation, when subjected to a freeze-drying process. The protective role of trehalose, lactose, glucose, mannitol and sucrose, known for their cryo/lyoprotective effect, was tested by addition of different concentrations to liposomes. Sucrose, in a concentration dependent manner (8:1 sugar:lipids mass ratio) proved to be a suitable cryo/lyoprotectant of these liposomes. Effectively, this saccharide prevents the fusion or/and aggregation of the liposomal formulation, protecting the integrity of the freeze-dried empty liposomes. The liposomal formulation containing sucrose was studied in terms of morphology, concentration, and anticancer drugs retention ability. The study involved two drugs encapsulated in the aqueous core, methotrexate (MTX) and doxorubicin (DOX), and one drug located in the lipid bilayer, tamoxifen (TAM). After the freeze-drying process, liposomes with sucrose encapsulating drugs revealed high physical stability, maintaining their narrow and monodisperse character, however high leakage of the drugs encapsulated in the aqueous core was observed. Otherwise, no significant drug leakage was detected on liposomes containing the TAM, which maintained its biological activity after the freeze-drying process. These findings reveal that sucrose is a good candidate for the cryo/lyoprotection of liposomes with drugs located in the lipid bilayer.

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“…Based on the reports, the lyoprotectants can effectively reduce the influence by these lyophilization process. 22 ( Figure 3 ). Two different cryoprotectants, trehalose and mannitol, were used to prevent liposome instability during freeze-drying.…”

Section: Resultsmentioning

confidence: 99%

<p>Long-Circulating Thermosensitive Liposomes for the Targeted Drug Delivery of Oxaliplatin</p>

et al. 2020

IJN

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Introduction Oxaliplatin (L-OHP) is a well-known third-generation platinum anticancer drug with severe systemic- and neuro-toxicity. The main objective of the current research was to develop a targeted long-circulating thermosensitive smart-release liposome (LCTL) system for better therapeutic efficacy and less toxicity. Methods The reverse-phase evaporation method (REV) was used to prepare L-OHP loaded LCTL (L-OHP/LCTL). The physical characteristics were evaluated including encapsulation efficiency (EE), size, zeta potential and stability. The release behavior, cytotoxicity and in vivo evaluation were also carried out. Results EE of LCTL was around 25% with a uniform size distribution, and LCTL achieved almost complete release at 42°C while it was only 10% at 37°C. Moreover, the LCTL showed significantly higher cytotoxicity at 42°C than that at 37°C. The in vivo results indicated LCTL could target tumors and enhance retention for more than 24 h, thereby enhancing anti-tumor efficacy on 4T1-bearing mice. Discussion These results indicated that LCTL not only possessed a prolonged circulation time but it also enhanced accumulation and achieved selective release at the tumor sites. Conclusively, LCTL could serve as a promising carrier for oxaliplatin delivery to treat solid tumors.

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Formulation Optimization of Freeze-Dried Long-Circulating Liposomes and In-Line Monitoring of the Freeze-Drying Process Using an NIR Spectroscopy Tool

Cited by 42 publications

References 53 publications

Lyophilization of Liposomal Formulations: Still Necessary, Still Challenging

Lyophilization of Liposomal Formulations: Still Necessary, Still Challenging

Protective Effect of Saccharides on Freeze-Dried Liposomes Encapsulating Drugs

<p>Long-Circulating Thermosensitive Liposomes for the Targeted Drug Delivery of Oxaliplatin</p>

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