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Environmental Research Dec 2023The site-specific delivery of drugs, especially anti-cancer drugs has been an interesting field for researchers and the reason is low accumulation of cytotoxic drugs in... (Review)
Review
The site-specific delivery of drugs, especially anti-cancer drugs has been an interesting field for researchers and the reason is low accumulation of cytotoxic drugs in cancer cells. Although combination cancer therapy has been beneficial in providing cancer drug sensitivity, targeted delivery of drugs appears to be more efficient. One of the safe, biocompatible and efficient nano-scale delivery systems in anti-cancer drug delivery is liposomes. Their particle size is small and they have other properties such as adjustable physico-chemical properties, ease of functionalization and high entrapment efficiency. Cisplatin is a chemotherapy drug with clinical approval in patients, but its accumulation in cancer cells is low due to lack of targeted delivery and repeated administration results in resistance development. Gene and drug co-administration along with cisplatin/paclitaxel have resulted in increased sensitivity in tumor cells, but there is still space for more progress in cancer therapy. The delivery of cisplatin/paclitaxel by liposomes increases accumulation of drug in tumor cells and impairs activity of efflux pumps in promoting cytotoxicity. Moreover, phototherapy along with cisplatin/paclitaxel delivery can increase potential in tumor suppression. Smart nanoparticles including pH-sensitive nanoparticles provide site-specific delivery of cisplatin/paclitaxel. The functionalization of liposomes can be performed by ligands to increase targetability towards tumor cells in mediating site-specific delivery of cisplatin/paclitaxel. Finally, liposomes can mediate co-delivery of cisplatin/paclitaxel with drugs or genes in potentiating tumor suppression. Since drug resistance has caused therapy failure in cancer patients, and cisplatin/paclitaxel are among popular chemotherapy drugs, delivery of these drugs mediates targeted suppression of cancers and prevents development of drug resistance. Because of biocompatibility and safety of liposomes, they are currently used in clinical trials for treatment of cancer patients. In future, the optimal dose of using liposomes and optimal concentration of loading cisplatin/paclitaxel on liposomal nanocarriers in clinical trials should be determined.
Topics: Humans; Liposomes; Cisplatin; Paclitaxel; Antineoplastic Agents; Drug Delivery Systems; Neoplasms; Cell Line, Tumor
PubMed: 37734579
DOI: 10.1016/j.envres.2023.117111 -
Journal of Nanoscience and... Jan 2011Phospholipid vesicles encapsulating magnetic nanoparticles (liposome complexes) have been prepared for targeting a drug to a specific organ using a magnetic force, as...
Phospholipid vesicles encapsulating magnetic nanoparticles (liposome complexes) have been prepared for targeting a drug to a specific organ using a magnetic force, as well as for local hyperthermia therapy. Liposome complexes are also an ideal platform for use as contrast agents of magnetic resonance imaging (MRI). We describe the preparation and characterization of liposomes containing magnetite. These liposomes were obtained by thin film hydration method and Fe3O4 nanoparticles were synthesized by coprecipitation method. They were characterized by an electrophoretic light scattering spectrophotometer, the liposome complexes were subsequently coated using chitosan. We have further investigated the ability of the above formulation for drug delivery and MRI applications. We are specifically interested in evaluating our liposome complexes for drug therapy; hence, we selected paclitaxel for the combination study. The amount of paclitaxel was measured at 227 nm using a UV-Vis spectrophotometer. Cytotoxicity of liposome complexes was treated with the various concentrations of paclitaxel in PC3 cell lines. The structure and properties of liposome complexes were analyzed by FT-IR, XRD and VSM. The particle size was analyzed by TEM and DLS.
Topics: Cell Line, Tumor; Cell Survival; Chitosan; Drug Delivery Systems; Ferric Compounds; Humans; Liposomes; Magnetic Resonance Spectroscopy; Metal Nanoparticles; Microscopy, Electron, Transmission; Nanoconjugates; Paclitaxel; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction
PubMed: 21446568
DOI: 10.1166/jnn.2011.3267 -
International Journal of Nanomedicine 2020Breast cancer is the leading cause of cancer death in women. Chemotherapy to inhibit the proliferation of cancer cells is considered to be the most important therapeutic...
BACKGROUND
Breast cancer is the leading cause of cancer death in women. Chemotherapy to inhibit the proliferation of cancer cells is considered to be the most important therapeutic strategy. The development of long-circulating PEG and targeting liposomes is a major advance in drug delivery. However, the techniques used in liposome preparation mainly involve conventional liposomes, which have a short half-life, high concentrations in the liver and spleen reticuloendothelial system, and no active targeting.
METHODS
Four kinds of paclitaxel liposomes were prepared and characterized by various analytical techniques. The long-term targeting effect of liposomes was verified by fluorescence detection methods in vivo and in vitro. Pharmacokinetic and acute toxicity tests were conducted in ICR mice to evaluate the safety of different paclitaxel preparations. The antitumor activity of ES-SSL-PTX was investigated in detail using in vitro and in vivo human breast cancer MCF-7 cell models.
RESULTS
ER-targeting liposomes had a particle size of 137.93±1.22 nm and an acceptable encapsulation efficiency of 88.07±1.25%. The liposome preparation is best stored at 4°C, and is stable for up to 48 hrs. Cytotoxicity test on MCF-7 cells demonstrated the stronger cytotoxic activity of liposomes in comparison to free paclitaxel. We used the near-infrared fluorescence imaging technique to confirm that ES-SSL-PTX was effectively targeted and could quickly and specifically identify the tumor site. Pharmacokinetics and acute toxicity in vivo experiments were carried out. The results showed that ES-SSL-PTX could significantly prolong the half-life of the drug, increase its circulation time in vivo, improve its bioavailability and reduce its toxicity and side effects. ES-SSL-PTX can significantly improve the pharmacokinetic properties of paclitaxel, avoid allergic reaction of the original solvent, increase antitumor efficacy and reduce drug toxicity and side effects.
CONCLUSION
ES-SSL-PTX has great potential for improving the treatment of breast cancer, thereby improving patient prognosis and quality of life.
Topics: Animals; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Cell Line, Tumor; Drug Delivery Systems; Female; Half-Life; Humans; Liposomes; MCF-7 Cells; Mice, Inbred BALB C; Mice, Inbred ICR; Paclitaxel; Toxicity Tests, Acute; Xenograft Model Antitumor Assays
PubMed: 32158208
DOI: 10.2147/IJN.S228715 -
Colloids and Surfaces. B, Biointerfaces May 2016Paclitaxel and rapamycin have been reported to act synergistically to treat breast cancer. Albeit paclitaxel is available for breast cancer treatment, the most commonly...
Paclitaxel and rapamycin have been reported to act synergistically to treat breast cancer. Albeit paclitaxel is available for breast cancer treatment, the most commonly used formulation in the clinic presents side effects, limiting its use. Furthermore, both drugs present pharmacokinetics drawbacks limiting their in vivo efficacy and clinic combination. As an alternative, drug delivery systems, particularly liposomes, emerge as an option for drug combination, able to simultaneously deliver co-loaded drugs with improved therapeutic index. Therefore, the purpose of this study is to develop and characterize a co-loaded paclitaxel and rapamycin liposome and evaluate it for breast cancer efficacy both in vitro and in vivo. Results showed that a SPC/Chol/DSPE-PEG (2000) liposome was able to co-encapsulate paclitaxel and rapamycin with suitable encapsulation efficiency values, nanometric particle size, low polydispersity and neutral zeta potential. Taken together, FTIR and thermal analysis evidenced drug conversion to the more bioavailable molecular and amorphous forms, respectively, for paclitaxel and rapamycin. The pegylated liposome exhibited excellent colloidal stability and was able to retain drugs encapsulated, which were released in a slow and sustained fashion. Liposomes were more cytotoxic to 4T1 breast cancer cell line than the free drugs and drugs acted synergistically, particularly when co-loaded. Finally, in vivo therapeutic evaluation carried out in 4T1-tumor-bearing mice confirmed the in vitro results. The co-loaded paclitaxel/rapamycin pegylated liposome better controlled tumor growth compared to the solution. Therefore, we expect that the formulation developed herein might be a contribution for future studies focusing on the clinical combination of paclitaxel and rapamycin.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Biological Availability; Cell Line, Tumor; Cell Survival; Drug Delivery Systems; Female; Liposomes; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Microscopy, Electron, Transmission; Paclitaxel; Phosphatidylethanolamines; Polyethylene Glycols; Sirolimus; Spectroscopy, Fourier Transform Infrared; Survival Analysis; Treatment Outcome
PubMed: 26836480
DOI: 10.1016/j.colsurfb.2016.01.032 -
European Journal of Cancer (Oxford,... May 2010To investigate the feasibility, pharmacokinetics, efficacy and toxicity of intrapleural paclitaxel liposome injection in non-small cell lung cancer (NSCLC) patients with...
PURPOSE
To investigate the feasibility, pharmacokinetics, efficacy and toxicity of intrapleural paclitaxel liposome injection in non-small cell lung cancer (NSCLC) patients with malignant pleural effusions.
PATIENTS AND METHODS
Twelve of 15 NSCLC patients with malignant pleural effusions were treated with paclitaxel liposome and three were treated with free paclitaxel. Adequate pleural fluid, blood and urine were collected for pharmacokinetic study. The clinical efficacy and toxicity were synthetically evaluated according to the correlative criteria.
RESULTS
The overall toxicity of paclitaxel liposome was lower than that of free paclitaxel. In the patients treated with paclitaxel liposome, there were minimal local chest pain, anaphylaxis, anaemia, neutropaenia and hepatotoxicity. The complete response rates of pleural effusion at the first, second, third and sixth month were, respectively, 27.3%, 18.2%, 9.1% and 9.1%, and overall response rates were 90.9%, 72.7%, 63.6% and 54.5%, respectively. Pharmacokinetic study showed that mean C(max,IP), T(1/2) and AUC(0-->96,IP) in pleural fluid were, respectively, about 2-fold, 2-fold and 2.5-fold than those of free paclitaxel, and AUC(0-->96,Pla) in plasma was also much higher than that of free paclitaxel, however, excretory rate in 24h from urine was lower than that of free paclitaxel.
CONCLUSIONS
This study demonstrated that paclitaxel liposome was a more useful agent than free paclitaxel for the treatment of malignant pleural effusions because of its relatively low toxicity and distinct pharmacokinetic characteristics. The phase II study of a large number of patients was recommended to confirm this finding.
Topics: Adult; Aged; Antineoplastic Agents, Phytogenic; Dose-Response Relationship, Drug; Feasibility Studies; Female; Humans; Liposomes; Lung Neoplasms; Male; Middle Aged; Paclitaxel; Pleural Effusion, Malignant; Treatment Outcome
PubMed: 20207133
DOI: 10.1016/j.ejca.2010.02.002 -
ACS Applied Materials & Interfaces Mar 2022Cancer-associated fibroblasts (CAFs), an important type of stromal cells in the tumor microenvironment (TME), are responsible for creating physical barriers to drug...
Sequential Delivery of Quercetin and Paclitaxel for the Fibrotic Tumor Microenvironment Remodeling and Chemotherapy Potentiation via a Dual-Targeting Hybrid Micelle-in-Liposome System.
Cancer-associated fibroblasts (CAFs), an important type of stromal cells in the tumor microenvironment (TME), are responsible for creating physical barriers to drug delivery and penetration in tumor tissues. Thus, effectively downregulating CAFs to destroy the physical barrier may allow enhanced penetration and accumulation of therapeutic drugs, thereby improving therapeutic outcomes. Herein, a matrix metalloproteinase (MMP)-triggered dual-targeting hybrid micelle-in-liposome system (RPM@NLQ) was constructed to sequentially deliver quercetin (Que) and paclitaxel (PTX) for fibrotic TME remodeling and chemotherapy potentiation. Specifically, antifibrotic Que and small-sized RGD-modified micelles containing PTX (RPM) were co-encapsulated into MMP-sensitive liposomes, and the liposomes were further adorned with the NGR peptide (NL) as the targeting moiety. The resulting RPM@NLQ first specifically accumulated at the tumor site under the guidance of the NGR peptide after intravenous administration and then released Que and RPM in response to the extensive expression of MMP in the TME. Subsequently, Que was retained in the stroma to remarkably downregulate fibrosis and decrease the stromal barrier by downregulating Wnt16 expression in CAFs, which further resulted in a significant increase of RPM for deeper tumor. Thus, RPM could precisely target and kill breast cancer cells locally. Consequently, prolonged blood circulation, selective cascade targeting of tumor tissue and tumor cells, enhanced penetration, and excellent antitumor efficacy have been demonstrated in vitro and in vivo. In conclusion, as-designed sequential delivery systems for fibrotic TME remodeling and chemotherapy potentiation may provide a promising adjuvant therapeutic strategy for breast and other CAF-rich tumors.
Topics: Cell Line, Tumor; Drug Delivery Systems; Fibrosis; Humans; Liposomes; Micelles; Paclitaxel; Quercetin; Tumor Microenvironment
PubMed: 35175043
DOI: 10.1021/acsami.1c23166 -
Zhongguo Yi Xue Ke Xue Yuan Xue Bao.... Jun 2014To compare the efficacy and safety between liposome-paclitaxel plus carboplatin (LPC) and paclitaxel plus carboplatin (PC) as first-line treatment for advanced non-small... (Comparative Study)
Comparative Study Randomized Controlled Trial
Comparison of efficacy and safety between liposome-paclitaxel injection plus carboplatin and paclitaxel plus carboplatin as first line treatment in advanced non-small cell lung cancer.
OBJECTIVE
To compare the efficacy and safety between liposome-paclitaxel plus carboplatin (LPC) and paclitaxel plus carboplatin (PC) as first-line treatment for advanced non-small cell lung cancer (NSCLC).
METHODS
Totally 54 chemotherapy-naive NSCLC patients were equally and randomly assigned into LPC group and PC group. Liposome-paclitaxel was injected on D1 at a dosage of 175 mg/m(2); the same dose and administration with paclitaxel injection in the PC group for a maximum of 2 cycles. The efficacy and adverse reactions after 2 cycles of chemotherapy were compared between these two groups.
RESULTS
The overall response rate (CR+PR) was 44.4% in the LPC group and 33.3% in the PC group after 2 cycles of chemotherapy respectively (P=0.577). In the LPC group and PC group, the incidences of myelodepression was 81.5% and 63.0%, respectively (P=0.080), gastrointestinal toxicity was 96.3% and 77.8% respectively (P=0.100), and allergic reactions was 0 and 11.1%, respectively (P=0.000). The median time to progression was 6 months and 5 months, respectively (P=0.420).
CONCLUSION
LPC group has the same efficacy with PC group and less adverse reactions than PC group.
Topics: Adult; Aged; Carboplatin; Carcinoma, Non-Small-Cell Lung; Female; Humans; Liposomes; Lung Neoplasms; Male; Middle Aged; Paclitaxel; Treatment Outcome
PubMed: 24997825
DOI: 10.3881/j.issn.1000-503X.2014.03.014 -
Head & Neck Apr 2017Vascular endothelial growth factor (VEGF) plays an important role in the formation of capillary blood vessels. The purpose of this study was to evaluate the inhibitory... (Comparative Study)
Comparative Study
BACKGROUND
Vascular endothelial growth factor (VEGF) plays an important role in the formation of capillary blood vessels. The purpose of this study was to evaluate the inhibitory effect of VEGF-targeted paclitaxel (PTX)-loaded liposome microbubbles (VTPLLMs) on the proliferation of human epidermoid (Hep-2) laryngeal squamous cell carcinoma (SCC).
METHODS
Six groups were randomly divided. The inhibitory effects on Hep-2 proliferation were assessed by a methylthiazol tetrazolium (MTT) method. The cell cycle distributions were investigated by flow cytometry. The expression variations of VEGF and caspase-3 were compared by Western blotting.
RESULTS
Proliferation of Hep-2 in the VTPLLM+ultrasound group was significantly inhibited, and flow cytometry showed that the Hep-2 cells were significantly blocked at stage G2/M compared with other groups. Moreover, Western blotting showed VEGF expression was downregulated and caspase-3 expression was upregulated.
CONCLUSION
VTPLLMs can efficiently inhibit tumor cell proliferation and outperform nontargeted microbubbles or PTX. © 2017 Wiley Periodicals, Inc. Head Neck 39: 656-661, 2017.
Topics: Apoptosis; Blotting, Western; Carcinoma, Squamous Cell; Cell Proliferation; Colorimetry; Flow Cytometry; Hep G2 Cells; Humans; Laryngeal Neoplasms; Liposomes; Microbubbles; Molecular Targeted Therapy; Paclitaxel; Tumor Cells, Cultured; Vascular Endothelial Growth Factor A
PubMed: 28106938
DOI: 10.1002/hed.24648 -
Molecular Pharmaceutics May 2014Combining chemotherapeutics is a promising method of improving cancer treatment; however, the clinical success of combination therapy is limited by the distinct...
Combining chemotherapeutics is a promising method of improving cancer treatment; however, the clinical success of combination therapy is limited by the distinct pharmacokinetics of combined drugs, which leads to nonuniform distribution. In this study, we report a new robust approach to load two drugs with different hydrophilicities into a single cross-linked multilamellar liposomal vesicle (cMLV) to precisely control the drug ratio that reaches the tumor in vivo. The stability of cMLVs improves the loading efficiency and sustained release of doxorubicin (Dox) and paclitaxel (PTX), maximizing the combined therapeutic effect and minimizing the systemic toxicity. Furthermore, we show that the cMLV formulation maintains specific drug ratios in vivo for over 24 h, enabling the ratio-dependent combination synergy seen in vitro to translate to in vivo antitumor activity and giving us control over another parameter important to combination therapy. This combinatorial delivery system may provide a new strategy for synergistic delivery of multiple chemotherapeutics with a ratiometric control over encapsulated drugs to treat cancer and other diseases.
Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Doxorubicin; Drug Synergism; Female; Humans; Liposomes; Mice; Mice, Inbred BALB C; Nanomedicine; Paclitaxel; Xenograft Model Antitumor Assays
PubMed: 24673622
DOI: 10.1021/mp5000373 -
Molecules (Basel, Switzerland) Nov 2022A series of novel paclitaxel derivatives modified by boronic acid according to the characteristics of the interaction between RB(OH)2 and different strapping agents of...
A series of novel paclitaxel derivatives modified by boronic acid according to the characteristics of the interaction between RB(OH)2 and different strapping agents of intraliposomal aqueous phase were designed and synthesized, which were then used to develop remote poorly water-soluble drugs loading into liposomes. Meanwhile, we screened nineteen paclitaxel boronic acid derivatives for their cytotoxic activities against three cancer cell lines (A549, HCT-116 and 4T1) and one normal cell line (LO2), and performed liposome formulation screening of active compounds. Among all the compounds, the liposome of 4d, with excellent drug-encapsulated efficiency (>95% for drug-to-lipid ratio of 0.1 w/w), was the most stable. Furthermore, the liposomes of compound 4d (8 mg/kg, 4 times) and higher dose of compound 4d (24 mg/kg, 4 times) showed better therapeutic effect than paclitaxel (8 mg/kg, 4 times) in the 4T1 tumor model in vivo, and the rates of tumor inhibition were 74.3%, 81.9% and 58.5%, respectively. This study provided a reasonable design strategy for the insoluble drugs to improve their drug loading into liposomes and anti-tumor effect in vivo.
Topics: Liposomes; Paclitaxel; Drug Stability; Boronic Acids
PubMed: 36432067
DOI: 10.3390/molecules27227967