Current status of pH-sensitive liposomes in drug delivery

Strategies used to enhance liposome-mediated drug delivery in vivo include the enhancement of stability and circulation time in the bloodstream, targeting to specific tissues or cells, and facilitation of intracytoplasmic delivery. pH-sensitive liposomes have been developed to mediate the introduction of highly hydrophilic molecules or macromolecules into the cytoplasm. These liposomes destabilize under acidic conditions found in the endocytotic pathway, and usually contain phosphatidylethanolamine (PE) and titratable stabilizing amphiphiles. Formulations without PE have also been developed. Encapsulated compounds are thought to be transported into the cytoplasm through destabilization of or fusion with the endosome membrane. Incorporation of a low mole percentage of poly(ethylene glycol) (PEG)-conjugated lipids into pHsensitive liposomes confers prolonged circulation times to these liposomes, which are otherwise cleared rapidly. While the incorporation of PEG -lipids reduces the pH-dependent release of encapsulated fluorescent markers in vitro, it does not hinder the cytoplasmic delivery of the markers per cell-associated liposome. This suggests that intracellular delivery is not dictated simply by the destabilization of the liposomes. Antibodies or ligands to cell surface receptors can be coupled to pH-sensitive or sterically stabilized pH-sensitive liposomes for targeting. pH-sensitive liposomes have been used to deliver anticancer drugs, antibiotics, antisense oligonucleotides, ribozymes, plasmids, proteins and peptides to cells in culture or in vivo. D

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“…Such properties determine the liposome efficacy to mediate cytoplasmic delivery of the encapsulated molecules [1,2,25].…”

Section: Biophysical Properties Underlying the Phsensitivity Of Liposmentioning

confidence: 99%

On the formulation of pH-sensitive liposomes with long circulation times

Simões

Moreira

Fonseca

et al. 2004

Advanced Drug Delivery Reviews

434

244

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“…Most nanoparticles currently being used are successful by reducing side‐effects or as a means to solubilize hydrophobic drugs to induce fewer side effects 24. However, there has been significant preclinical work focused on developing new strategies for improving the delivery and efficacy of drugs using nanoparticles that are responsive to external stimuli such as heat,25, 26, 27, 28 light,29, 30, 31, 32, 33 ultrasound34 or tumor environment factors such as lower pH35, 36, 37, 38 or expression of certain enzymes 39, 40…”

Section: Introductionmentioning

confidence: 99%

Chemophototherapy: An Emerging Treatment Option for Solid Tumors

et al. 2016

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Near infrared (NIR) light penetrates human tissues with limited depth, thereby providing a method to safely deliver non‐ionizing radiation to well‐defined target tissue volumes. Light‐based therapies including photodynamic therapy (PDT) and laser‐induced thermal therapy have been validated clinically for curative and palliative treatment of solid tumors. However, these monotherapies can suffer from incomplete tumor killing and have not displaced existing ablative modalities. The combination of phototherapy and chemotherapy (chemophototherapy, CPT), when carefully planned, has been shown to be an effective tumor treatment option preclinically and clinically. Chemotherapy can enhance the efficacy of PDT by targeting surviving cancer cells or by inhibiting regrowth of damaged tumor blood vessels. Alternatively, PDT‐mediated vascular permeabilization has been shown to enhance the deposition of nanoparticulate drugs into tumors for enhanced accumulation and efficacy. Integrated nanoparticles have been reported that combine photosensitizers and drugs into a single agent. More recently, light‐activated nanoparticles have been developed that release their payload in response to light irradiation to achieve improved drug bioavailability with superior efficacy. CPT can potently eradicate tumors with precise spatial control, and further clinical testing is warranted.

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“…Drug release systems triggered in response to local environmental conditions such as temperature (13,14), specific enzymes (15,16), and pH (17)(18)(19)(20)(21) seem to be an optional approach to circumvent MRD-associated problems. pH-sensitive drug delivery systems have been used for tumor treatment, utilizing the slightly acidic conditions (pH 6.5−7.2) of the extracellular tumor space (17)(18)(19)(20)(21) and the higher acidity in endolysosomal compartments (22).…”

Section: Introductionmentioning

confidence: 99%

“…pH-sensitive drug delivery systems have been used for tumor treatment, utilizing the slightly acidic conditions (pH 6.5−7.2) of the extracellular tumor space (17)(18)(19)(20)(21) and the higher acidity in endolysosomal compartments (22). pH-sensitive liposomes (21) are one such delivery system.…”

Section: Introductionmentioning

confidence: 99%

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Doxorubicin Loaded pH-sensitive Micelle: Antitumoral Efficacy against Ovarian A2780/DOXR Tumor

Kim¹,

Lee²,

Park³

et al. 2008

Pharm Res

107

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Purpose-To evaluate pH-sensitive mixed micelles for multidrug resistant (MDR) ovarian tumor targeting and optical imaging of solid tumors.Method-Doxorubicin (DOX) encapsulated pH-sensitive mixed micelles composed of poly(Lhistidine) (MW 5K)-b-PEG(MW 2K) and poly(L-lactic acid)(3K)-b-PEG (2K)-folate (PHSM-f) were prepared. Folate receptor-mediated endocytosis, drug uptake, endosomal disruption and cell viability were investigated at the cellular level. For in vivo tumor growth inhibition tests, multidrug resistant ovarian A2780/DOX R xenografted nude mice were used. Optical imaging was performed by using a Cy5.5 fluorescence dye-labeled mixed micelle system. Cy5.5 fluorescence intensity at the tumor site was measured in KB epidermoid xenografted nude mice.Results-In vitro cell viability and drug distribution in the cytoplasm demonstrated the significantly superior efficacy of PHSM-f to free DOX and a control sample of DOX loaded pH-insensitive micelle composed of poly(L-lactic acid)(3K)-b-PEG(2K)/poly(L-lactic acid)(3K)-b-PEG(2K)-folate (80/20 wt/wt%) (PHIM-f). The mechanisms of these results were proved by folate receptor mediated endocytosis of micelle and endosomal disruption function by it. In addition, the optical imaging demonstrated the future application of the diagnositic area. PHSM-f inhibited the growth of multidrug resistant ovarian tumors efficiently in mice, with minimum weight loss.Conclusions-The pH-sensitive mixed micelle system demonstrates effective antitumor efficacy against the multidrug resistant ovarian tumor A2780/DOX R .

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Current status of pH-sensitive liposomes in drug delivery

Cited by 438 publications

References 335 publications

On the formulation of pH-sensitive liposomes with long circulation times

On the formulation of pH-sensitive liposomes with long circulation times

Chemophototherapy: An Emerging Treatment Option for Solid Tumors

Doxorubicin Loaded pH-sensitive Micelle: Antitumoral Efficacy against Ovarian A2780/DOXR Tumor

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