Mechanistic model and analysis of doxorubicin release from liposomal formulations

Fugit, Kyle D.; Xiang, Tian‐Xiang; Choi, Du Hyung; Kangarlou, Sogol; Csuhai, Eva; Bummer, Paul M.; Anderson, Bradley D.

doi:10.1016/j.jconrel.2015.08.024

Cited by 46 publications

(27 citation statements)

References 38 publications

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“…An additional release from the formulations was observed after 24 h of study; however, PEGylated liposomes showed higher retention of the radiotracer. In fact, the presence of PEG could lead to a slight increase in liposome stability, resulting in a higher retention of the encapsulated drug [33, 34]. Nevertheless, even for liposomes with no PEG coating, a low 99m Tc-HYNIC-βAla-Bombesin (7–14) leakage was observed (~ 70% of the radioactive probe remains stable into the liposome for up to 24 h).…”

Section: Discussionmentioning

confidence: 99%

Influence of PEG coating on the biodistribution and tumor accumulation of pH-sensitive liposomes

Nunes

Fernandes

Cavalcante

et al. 2018

Drug Deliv. and Transl. Res.

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Liposomes are lipid vesicles widely used as nanocarriers in targeted drug delivery systems for therapeutic and/or diagnostic purposes. A strategy to prolong the blood circulation time of the liposomes includes the addition of a hydrophilic polymer polyethylene glycol (PEG) moiety onto the surface of the vesicle. Several studies claim that liposome PEGylation by a single chain length or a combination of PEG with different chain lengths may alter the liposomes' pharmacokinetic properties. Therefore, the purpose of this study was to evaluate the influence of PEG on the biodistribution of pH-sensitive liposomes in a tumor-bearing animal model. Three liposomal formulations (PEGylated or not) were prepared and validated to have a similar mean diameter, monodisperse distribution, and neutral zeta potential. The pharmacokinetic properties of each liposome were evaluated in healthy animals, while the biodistribution and scintigraphic images were evaluated in tumor-bearing mice. High tumor-to-muscle ratios were not statistically different between the PEGylated and non-PEGylated liposomes. While PEGylation is a well-established strategy for increasing the blood circulation of nanostructures, in our study, the use of polymer coating did not result in a better in vivo profile. Further studies must be carried out to confirm the feasibility of the non-PEGylated pH-sensitive liposomes for tumor treatment.

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Section: Discussionmentioning

confidence: 99%

Influence of PEG coating on the biodistribution and tumor accumulation of pH-sensitive liposomes

Nunes

Fernandes

Cavalcante

et al. 2018

Drug Deliv. and Transl. Res.

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“…The presence of precipitated drug within liposomes has been described previously for vincristine ( 13 ), doxorubicin ( 2 , 14 ), topotecan ( 2 ) and vinorelbin ( 2 , 33 ). In contrast to these studies where the ciprofloxacin formed nanocrystals in response to freeze-thaw, in the other studies the drug formed precipitates during the loading process.…”

Section: Discussionmentioning

confidence: 99%

“…It has also been previously noted that precipitated drug within liposome vesicles leads to a slower release and a longer in vivo half-life ( 2 , 13 ). The rationale for the slower release has been the lower soluble intravesicular drug concentration which is the driving force for drug transport across the liposome membrane ( 2 , 13 , 14 , 33 ). If the rate of drug dissolution is fast compared to transport across the lipid membrane, then an almost zero order rate of release can be obtained as was demonstrated for doxorubicin ( 14 ) and vinorelbin ( 33 ).…”

Section: Discussionmentioning

confidence: 99%

“…The objective of these studies was to further investigate the ciprofloxacin nanocrystal formation processes within the liposomal formulation with the aim to identify procedures that could be used to alter the size or shape of the crystalline drug in a controlled manner. The formation of drug nanocrystals results in lower soluble drug concentrations within the liposomes which would be expected to reduce the rate of drug release across the lipid membrane barrier as has previously been shown for liposomal formulations of precipitated vincristine ( 13 ) and doxorubicin ( 14 ). The mechanistic model for release of precipitated doxorubicin sulfate from the liposomes predicts that dissolution of the precipitated drug is not rate-limiting; in other words, the driving force for release is the soluble intra-vesicular drug concentration which remains constant if the rate of drug dissolution matches the release of drug from the liposomes ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

“…The formation of drug nanocrystals results in lower soluble drug concentrations within the liposomes which would be expected to reduce the rate of drug release across the lipid membrane barrier as has previously been shown for liposomal formulations of precipitated vincristine ( 13 ) and doxorubicin ( 14 ). The mechanistic model for release of precipitated doxorubicin sulfate from the liposomes predicts that dissolution of the precipitated drug is not rate-limiting; in other words, the driving force for release is the soluble intra-vesicular drug concentration which remains constant if the rate of drug dissolution matches the release of drug from the liposomes ( 14 ). Forming ciprofloxacin nanocrystals with different sizes or shapes, as will be attempted in these studies, may provide evidence of whether drug dissolution is rate-limiting for this liposomal system.…”

Section: Introductionmentioning

confidence: 99%

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Tuning Ciprofloxacin Release Profiles from Liposomally Encapsulated Nanocrystalline Drug

Cipolla

Eastman³

et al. 2016

Pharm Res

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PurposeIn order to attenuate the drug release rate, a single freeze-thaw step was previously shown to convert encapsulated drug into a single nanocrystal within each liposome vesicle. The goal of this study was to alter the nanocrystalline character, and thus the drug encapsulation state and release profile, by addition of surfactant prior to freeze-thaw.MethodsA liposomal ciprofloxacin (CFI) formulation was modified by the addition of surfactant and frozen. After thawing, these formulations were characterized in terms of drug encapsulation by centrifugation-filtration, liposome structure by cryo-TEM imaging, vesicle size by dynamic light scattering, and in vitro release (IVR) performance.ResultsThe addition of increasing levels of polysorbate 20 (0.05 to 0.4%) or Brij 30 (0.05 to 0.3%) to the CFI preparations followed by subsequent freeze-thaw, resulted in a greater proportion of vesicles without drug nanocrystals and reduced the extent of growth of the nanocrystals thus leading to modified release rates including an increase in the ratio of non-encapsulated to sustained release of drug.ConclusionsThis study provides another lever to achieve the desired release rate profile from a liposomal formulation by addition of surfactant and subsequent freeze-thaw, and thus may provide a personalized approach to treating patients.

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An Injectable Composite Co‐Assembled Dehydropeptide‐Based Magnetic/Plasmonic Lipogel for Multimodal Cancer Therapy

Veloso,

Vázquez‐González,

Spuch

et al. 2024

Adv Funct Materials

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Advancing therapeutic effectiveness through the strategic co‐delivery of drugs in a sequential manner represents a compelling strategy. However, achieving precise and selective release of chemotherapeutic agents remains a formidable challenge. In this study, a co‐assembled Arginine‐Glycine‐Aspartate (RGD)‐functionalized dehydropeptide‐based gel loaded with magnetic liposomes and mesoporous silica‐coated gold nanorods is introduced. This composite system serves as a sophisticated tool to independently modulate the release of doxorubicin and methotrexate. The gel's properties are intricately tuned by the incorporation of liposomes or nanorods and/or the co‐assembly with an RGD‐functionalized peptide. Furthermore, the combined effects of sequential drug release, photothermia, and magnetic hyperthermia synergistically enhance therapeutic efficacy against 3D cancer cell cultures. Noteworthy attributes of the gel include its ability to orthogonally trigger loaded drugs, along with features such as injectability, rapid gelation, self‐healing, and mechanical properties suitable for drug delivery. Consequently, this versatile multimodal platform emerges as a promising option for therapeutic applications, particularly in the context of cancer therapy.

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Mechanistic model and analysis of doxorubicin release from liposomal formulations

Cited by 46 publications

References 38 publications

Influence of PEG coating on the biodistribution and tumor accumulation of pH-sensitive liposomes

Influence of PEG coating on the biodistribution and tumor accumulation of pH-sensitive liposomes

Tuning Ciprofloxacin Release Profiles from Liposomally Encapsulated Nanocrystalline Drug

An Injectable Composite Co‐Assembled Dehydropeptide‐Based Magnetic/Plasmonic Lipogel for Multimodal Cancer Therapy

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