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Therapeutic Delivery Feb 2024This study aims to assess the efficacy of free and niosomes-loaded paclitaxel combined with the anti-diabetic drug metformin. Paclitaxel was successfully encapsulated...
This study aims to assess the efficacy of free and niosomes-loaded paclitaxel combined with the anti-diabetic drug metformin. Paclitaxel was successfully encapsulated in all niosome formulations, using microfluidic mixing, with a maximum encapsulation efficiency of 11.9%. The half maximal inhibitory concentration (IC) for free paclitaxel in T47D cells was significantly reduced from 0.2 to 0.048 mg/ml when combined with metformin 40 mg. The IC of paclitaxel was significantly reduced when loaded in niosomes to less than 0.06 mg/ml alone or with metformin. Paclitaxel combination (free or loaded into niosomes) with metformin significantly improved the anticancer efficacy of paclitaxel, which can serve as a method to reduce the paclitaxel dose and its associated side effects.
Topics: Paclitaxel; Liposomes; Metformin; Drug Compounding; Cell Line, Tumor
PubMed: 38214106
DOI: 10.4155/tde-2023-0089 -
International Journal of Nanomedicine 2016The use of radiosensitizers in clinical radiotherapy is limited by systemic toxicity. The biopolymeric, biodegradable, injectable liposome-in-gel-paclitaxel (LG-PTX)...
The use of radiosensitizers in clinical radiotherapy is limited by systemic toxicity. The biopolymeric, biodegradable, injectable liposome-in-gel-paclitaxel (LG-PTX) system was developed for regional delivery of the radiosensitizer paclitaxel (PTX), and its efficacy was evaluated with concurrent fractionated radiation. LG-PTX is composed of nano-sized drug-loaded fluidizing liposomes, which are incorporated into a porous biodegradable gellan hydrogel. This allows enhanced drug permeation while maintaining a localization of the drug depot. LG-PTX had an IC of 325±117 nM in B16F10 melanoma cells, and cytotoxicity with concurrent doses of fractionated radiation showed significant increase in apoptotic cells (75%) compared to radiation (39%) or LG-PTX (43%) alone. Peri-tumoral injection in tumor-bearing mice showed PTX localization in the tumor 2 hours after administration, with no drug detected in plasma or other organs. LG-PTX administration with doses of focal radiation (5×3 Gy) significantly reduced tumor volumes compared to control (6.4 times) and radiation alone (1.6 times) and improved animal survival. LG-PTX thus efficiently localizes the drug at the tumor site and synergistically enhances the effect of concurrent radiotherapy. This novel liposome-in-gel system can potentially be used as a platform technology for the delivery of radiosensitizing drugs to enhance the efficacy of chemoradiotherapy.
Topics: Animals; Antineoplastic Agents, Phytogenic; Cell Proliferation; Chemoradiotherapy; Drug Delivery Systems; Female; Gels; Liposomes; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Paclitaxel; Tumor Cells, Cultured
PubMed: 27942215
DOI: 10.2147/IJN.S110525 -
Molecular Medicine Reports Mar 2013The commercial drug paclitaxel (Taxol) may introduce hypersensitivity reactions associated with the polyethoxylated castor oil-ethanol solvent. To overcome these...
The commercial drug paclitaxel (Taxol) may introduce hypersensitivity reactions associated with the polyethoxylated castor oil-ethanol solvent. To overcome these problems, we developed a polyethoxylated castor oil-free, liposome-based alternative paclitaxel formulation, known as Lipusu. In this study, we performed in vitro and in vivo experiments to compare the safety profiles of Lipusu and Taxol, with special regard to hypersensitivity reactions. First, Swiss mice were used to determine the lethal dosages, and then to evaluate hypersensitivity reactions, followed by histopathological examination and enzyme-linked immunosorbent assays (ELISAs) of serum SC5b-9 and lung histamine. Additionally, healthy human serum was used to analyze in vitro complement activation. Finally, an MTT assay was used to determine the in vitro anti-proliferation activity. Our data clearly showed that Lipusu displayed a much higher safety margin and did not induce hypersensitivity or hypersensitivity-related lung lesions, which may be associated with the fact that Lipusu did not activate complement or increase histamine release in vivo. Moreover, Lipusu did not promote complement activation in healthy human serum in vitro, and demonstrated anti-proliferative activity against human cancer cells, similar to that of Taxol. Therefore, the improved formulation of paclitaxel, which exhibited a much better safety profile and comparable cytotoxic activity to Taxol, may bring a number of benefits to cancer patients.
Topics: Animals; Antineoplastic Agents, Phytogenic; Castor Oil; Cell Line, Tumor; Cell Survival; Chemistry, Pharmaceutical; Complement Activation; Complement Membrane Attack Complex; Complement System Proteins; Enzyme-Linked Immunosorbent Assay; Histamine; Humans; Hypersensitivity; Liposomes; Lung; Mice; Neoplasms; Paclitaxel
PubMed: 23291923
DOI: 10.3892/mmr.2013.1264 -
Journal of Biomedical Nanotechnology Aug 2018Liposome-microbubble complexes (LMC) have become a promising therapeutic carrier for ultrasound-triggered local drug release. However, it is still desirable for the...
Liposome-microbubble complexes (LMC) have become a promising therapeutic carrier for ultrasound-triggered local drug release. However, it is still desirable for the released drugs to be delivered to tumors as effectively as possible. Here, we fabricated iRGD-targeted paclitaxel-loaded liposome-microbubble complexes (iRGD-PTX-LMC) and investigated the feasibility of enhancing the local drug delivery to breast tumors by using these complexes along with ultrasound irradiation. Our results showed that iRGD-modified PTX-loaded liposomes (iRGD-PTX-PL) were successfully conjugated to the surface of microbubbles (MBs) through biotin-avidin linkage. The resulting iRGD-PTX-LMC retained the ultrasound imaging capability and showed effective ultrasound-triggered drug release. High cell affinity and enhanced drug delivery into tumor cells was confirmed for iRGD-PTX-LMC upon ultrasound exposure. Additionally, our data revealed that iRGD-PTX-LMC with ultrasound had a significantly better tumor growth inhibition effect than iRGD-PTX-PL or nontargeted PTX-LMC in not only in vitro but also in vivo studies. Histological examination indicated that the inhibition of tumor growth was caused by the increases in the drug concentration and the number of apoptotic tumor cells in tumor xenografts. In conclusion, our study revealed the great potential of iRGD-PTX-LMC as a new tool to enhance local drug delivery and significantly improve antitumor efficacy.
Topics: Breast Neoplasms; Cell Line, Tumor; Drug Delivery Systems; Humans; Liposomes; Microbubbles; Paclitaxel; Ultrasonography
PubMed: 29903054
DOI: 10.1166/jbn.2018.2594 -
Journal of Nanobiotechnology May 2021Porphyrin-lipids are versatile building blocks that enable cancer theranostics and have been applied to create several multimodal nanoparticle platforms, including...
BACKGROUND
Porphyrin-lipids are versatile building blocks that enable cancer theranostics and have been applied to create several multimodal nanoparticle platforms, including liposome-like porphysome (aqueous-core), porphyrin nanodroplet (liquefied gas-core), and ultrasmall porphyrin lipoproteins. Here, we used porphyrin-lipid to stabilize the water/oil interface to create porphyrin-lipid nanoemulsions with paclitaxel loaded in the oil core (PLNE-PTX), facilitating combination photodynamic therapy (PDT) and chemotherapy in one platform.
RESULTS
PTX (3.1 wt%) and porphyrin (18.3 wt%) were loaded efficiently into PLNE-PTX, forming spherical core-shell nanoemulsions with a diameter of 120 nm. PLNE-PTX demonstrated stability in systemic delivery, resulting in high tumor accumulation (~ 5.4 ID %/g) in KB-tumor bearing mice. PLNE-PTX combination therapy inhibited tumor growth (78%) in an additive manner, compared with monotherapy PDT (44%) or chemotherapy (46%) 16 days post-treatment. Furthermore, a fourfold reduced PTX dose (1.8 mg PTX/kg) in PLNE-PTX combination therapy platform demonstrated superior therapeutic efficacy to Taxol at a dose of 7.2 mg PTX/kg, which can reduce side effects. Moreover, the intrinsic fluorescence of PLNE-PTX enabled real-time tracking of nanoparticles to the tumor, which can help inform treatment planning.
CONCLUSION
PLNE-PTX combining PDT and chemotherapy in a single platform enables superior anti-tumor effects and holds potential to reduce side effects associated with monotherapy chemotherapy. The inherent imaging modality of PLNE-PTX enables real-time tracking and permits spatial and temporal regulation to improve cancer treatment.
Topics: Animals; Cell Line, Tumor; Drug Carriers; Drug Therapy; Emulsions; Humans; Lipids; Liposomes; Mice; Nanoparticles; Paclitaxel; Photochemotherapy; Polyethylene Glycols; Porphyrins; Therapeutic Uses; Xenograft Model Antitumor Assays
PubMed: 34034749
DOI: 10.1186/s12951-021-00898-1 -
Nanomedicine (London, England) Dec 2020To investigate the effect of liposomes containing the classical cytotoxic drugs paclitaxel and doxorubicin (Lipo-Pacli/Dox), against a metastatic breast cancer model....
To investigate the effect of liposomes containing the classical cytotoxic drugs paclitaxel and doxorubicin (Lipo-Pacli/Dox), against a metastatic breast cancer model. We also investigated if Lipo-Pacli/Dox was capable of reverting the tolerogenic environment of metastatic lesions. Immunogenic cell death induction by the Pacli/Dox combination was assessed . Antitumor activity and safety of Lipo-Pacli/Dox were evaluated using a 4T1 breast cancer mouse model : Lipo-Pacli/Dox, with a size of 189 nm and zeta potential of -5.01 mV, promoted immune system activation and partially controlled the progression of pulmonary metastasis. Lipo-Pacli/Dox was useful to control both primary tumor and lung metastasis in breast cancer (4T1) mice model. Additionally, Lipo-Pacli/Dox acts as an immunological modulator for this metastatic breast cancer model.
Topics: Animals; Antibiotics, Antineoplastic; Cell Line, Tumor; Doxorubicin; Liposomes; Lung Neoplasms; Lymphocytes; Mice; Mice, Inbred BALB C; Paclitaxel; Prognosis
PubMed: 33179587
DOI: 10.2217/nnm-2020-0201 -
International Journal of Pharmaceutics Nov 2014Interactions between paclitaxel and its squalenoyl prodrug with dimyristoylphosphatidylcholine (DMPC) monolayer at the air/water interface were studied. Paclitaxel is an...
Interactions between paclitaxel and its squalenoyl prodrug with dimyristoylphosphatidylcholine (DMPC) monolayer at the air/water interface were studied. Paclitaxel is an antineoplastic drug, largely used as anti-cancer agents. Because its low aqueous solubility, Cremophor EL is used as excipient for its formulation. However, it has been shown that Cremophor causes serious side effects. Several attempts have been made to develop a safer formulation such as the synthesis of lipophilic prodrug. In particular we have synthesized a paclitaxel prodrug obtained by conjugation with 1,1,2-trisnorsqualenoic acid to improve the physico-chemical properties of this antineoplastic drug. The miscibility of these compounds with DMPC monolayer were studied analyzing thermodynamic properties as well as excess Gibbs free energies, compressibility modulus and mixed monolayer isotherms. The results allowed to evaluate the spatial organization of the compounds and suggested that the prodrug can efficiently be incorporated in the DMPC monolayer.
Topics: Antineoplastic Agents; Chemistry, Pharmaceutical; Dimyristoylphosphatidylcholine; Liposomes; Paclitaxel; Prodrugs; Squalene
PubMed: 25234865
DOI: 10.1016/j.ijpharm.2014.09.022 -
ACS Applied Materials & Interfaces Dec 2022Novel approaches are required to address the urgent need to develop lipid-based carriers of paclitaxel (PTX) and other hydrophobic drugs for cancer chemotherapy....
Novel approaches are required to address the urgent need to develop lipid-based carriers of paclitaxel (PTX) and other hydrophobic drugs for cancer chemotherapy. Carriers based on cationic liposomes (CLs) with fluid (i.e., chain-melted) membranes (e.g., EndoTAG-1) have shown promise in preclinical and late-stage clinical studies. Recent work found that the addition of a cone-shaped poly(ethylene glycol)-lipid (PEG-lipid) to PTX-loaded CLs (CLs) promotes a transition to sterically stabilized, higher-curvature (smaller) nanoparticles consisting of a mixture of PEGylated CLs and PTX-containing fluid lipid nanodiscs (nanodiscs). These CLs and nanodiscs show significantly improved uptake and cytotoxicity in cultured human cancer cells at PEG coverage in the brush regime (10 mol % PEG-lipid). Here, we studied the PTX loading, circulation half-life, and biodistribution of systemically administered CLs and nanodiscs and assessed their ability to induce apoptosis in triple-negative breast-cancer-bearing immunocompetent mice. We focused on rather than lipid nanodiscs because of the significantly higher solubility of PTX in fluid membranes. At 5 and 10 mol % of a PEG-lipid (PEG5K-lipid, molecular weight of PEG 5000 g/mol), the mixture of PEGylated CLs and nanodiscs was able to incorporate up to 2.5 mol % PTX without crystallization for at least 20 h. Remarkably, compared to preparations containing 2 and 5 mol % PEG5K-lipid (with the PEG chains in the mushroom regime), the particles at 10 mol % (with PEG chains in the brush regime) showed significantly higher blood half-life, tumor penetration, and proapoptotic activity. Our study suggests that increasing the PEG coverage of CL-based drug nanoformulations can improve their pharmacokinetics and therapeutic efficacy.
Topics: Mice; Humans; Animals; Female; Paclitaxel; Liposomes; Tissue Distribution; Caspase 3; Polyethylene Glycols; Lipids; Breast Neoplasms; Drug Carriers; Cell Line, Tumor; Antineoplastic Agents, Phytogenic
PubMed: 36521233
DOI: 10.1021/acsami.2c17961 -
Yao Xue Xue Bao = Acta Pharmaceutica... Jan 2014In this study, we developed a novel liposome-silica hybrid nano-carrier for tumor combination therapy via oral route, using paclitaxel and cyclosporine as a model drug...
In this study, we developed a novel liposome-silica hybrid nano-carrier for tumor combination therapy via oral route, using paclitaxel and cyclosporine as a model drug pair. Optimization of the preparation of the drug-loading formulation and characterization of its physicochemical parameters and drug release profile were performed in vitro. Then in vivo pharmacodynamics and pharmacokinetics studies were performed. The results showed that the obtained formulation has a small particle size (mean diameter of 100.2 +/- 15.2 nm), a homogeneous distribution [the polydispersity index was (0.251 +/- 0.018)] and high encapsulation efficiency (90.15 +/- 2.47) % and (80.64 +/- 3.52) % for paclitaxel and cyclosporine respectively with a mild and easy preparation process. A sequential drug release trend of cyclosporine prior to palictaxel was observed. The liposome-silica hybrid nano-carrier showed good biocompatibility in vivo and co-delivery of cyclosporine and paclitaxel significantly enhanced the oral absorption of paclitaxel with improved anti-tumor efficacy, suggesting a promising approach for multi-drug therapy against tumor and other serious diseases via oral route.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Administration, Oral; Animals; Antineoplastic Agents, Phytogenic; Biological Availability; Cyclosporine; Drug Carriers; Female; Liposomes; Male; Mice; Nanoparticles; Neoplasm Transplantation; Paclitaxel; Particle Size; Random Allocation; Rats; Rats, Sprague-Dawley; Sarcoma 180; Silicon Dioxide; Tumor Burden
PubMed: 24783515
DOI: No ID Found -
Nanomedicine : Nanotechnology, Biology,... Apr 2017Tyroservatide (YSV) is a tripeptide that has been approved for clinical testing, as a new anticancer drug. In the current study, YSV-stearic acid (YSV-SA) was inserted...
Tyroservatide (YSV) is a tripeptide that has been approved for clinical testing, as a new anticancer drug. In the current study, YSV-stearic acid (YSV-SA) was inserted into the surface of d-alpha-tocopheryl polyethylene glycol 1000 succinate monoester (TPGS)-modified paclitaxel (PTX) liposomes (TP-Lip) to form YSV-conjugated TP-Lip (TYP-Lip). Both in vivo imaging and in vitro cell uptake analysis indicated that these modifications could increase tumor-targeting and cell uptake of the liposomes. Optimal antitumor effects were achieved via tail vein injections of TYP-Lip in MB-231 tumor-bearing nude mice. Overall, the formed TYP-Lip not only achieved a synergistic anticancer effect through YSV and PTX, but also improved tumor-targeting and exhibited further antitumor capabilities. These results indicated that combining biological (YSV) and chemotherapeutic (PTX) agents is an efficient combinatorial delivery strategy for enhanced tumor targeting and synergistic antitumor effects.
Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast; Breast Neoplasms; Cell Line, Tumor; Drug Combinations; Drug Delivery Systems; Female; Humans; Liposomes; Mice; Mice, Nude; Oligopeptides; Paclitaxel; Vitamin E
PubMed: 27845234
DOI: 10.1016/j.nano.2016.10.017