Albumin-bound Nanoparticle Research Articles

Comparing Neoadjuvant Nab-paclitaxel vs Paclitaxel Both Followed by Anthracycline Regimens in Women With ERBB2/HER2-Negative Breast Cancer—The Evaluating Treatment With Neoadjuvant Abraxane (ETNA) Trial

Studies of neoadjuvant chemotherapy regimens using anthracyclines followed by taxanes have reported a doubling of pathological complete remission (pCR) rates compared with anthracycline-based regimens alone. A reverse sequence did not reduce activity. Nab-paclitaxel is an albumin-bound nanoparticle of paclitaxel that allows for safe infusion without premedication, and its use led to a significantly higher rate of pCR in the GeparSepto trial. To determine whether nab-paclitaxel improves the outcomes of early and locally advanced human epidermal growth factor receptor 2 (ERBB2/HER2)-negative breast cancer compared with paclitaxel when delivered in a neoadjuvant setting. In this multicenter, open-label study, in collaboration with Grupo Español de Investigación en Cáncer de Mama (GEICAM) and Breast Cancer Research Center-Western Australia (BCRC-WA), patients with newly diagnosed and centrally confirmed ERBB2/HER2-negative breast cancer were recruited. Participants were randomly allocated to paclitaxel, 90 mg/m2 (349 patients), or nab-paclitaxel, 125 mg/m2 (346 patients). The 2 drugs were given on weeks 1, 2, and 3 followed by 1 week of rest for 4 cycles before 4 cycles of an anthracycline regimen per investigator choice. The primary end point was the rate of pCR, defined as absence of invasive cells in the breast and axillary nodes (ie, ypT0/is ypN0) at the time of surgery. A secondary end point was to assess tolerability and safety of the 2 regimens. From May 2013 to March 2015, 814 patients were registered to the study; 695 patients met central confirmation eligibility and were randomly allocated to receive either paclitaxel (349), or nab-paclitaxel (346) (median age, 50 years; range, 25-79 years). The intention-to-treat analysis of the primary end point pCR revealed that the improved pCR rate after nab-paclitaxel (22.5%) was not statistically significant compared with paclitaxel (18.6%; odds ratio [OR], 0.77; 95% CI, 0.52-1.13; P = .19). Overall, 38 of 335 patients (11.3%) 11.3% of patients had at least 1 serious adverse event in the paclitaxel arm and 54 of 337 patient (16.0%) in the nab-paclitaxel arm. Peripheral neuropathy of grade 3 or higher occurred in 6 of 335 patients (1.8%) and in 15 of 337 (4.5%), respectively. The improved rate of pCR after nab-paclitaxel was not statistically significant. The multivariate analysis revealed that tumor subtype (triple-negative vs luminal B-like) was the most significant factor (OR, 4.85; 95% CI, 3.28-7.18) influencing treatment outcome. clinicaltrials.gov Identifier: NCT01822314.

Abstract 4788: Abraxane eliminates cancer stem cells in triple-negative breast cancers

Abstract Triple-negative breast cancer (TNBC) represents about 20 percent of all breast cancers, with a poorer survival rate and being associated with high-grade tumors and the least favorable prognosis. Due to the absence of hormone receptors and Her2 receptor, no targeted therapy is available and chemotherapy is the standard treatment for TNBC patient. Paclitaxel is a widely used chemotherapy drug for various cancers with severe side effects due to its solvent. Abraxane is an albumin-bound nanoparticle of paclitaxel with less severe side effects. Here we investigated whether cancer stem cells (CSCs) in TNBC response differentially to abraxane and paclitaxel both in cell culture and xenograft mouse models. Using a series of human TNBC cell lines, we showed that there is no difference between solvent-based paclitaxel and abraxane in vitro in term of efficacy and eliminating cancer stem cells using MTS assay, mammosphere formation assay, and flow analysis of cancer stem cells. Interestingly, we demonstrated that abraxane shows superior efficacy than solvent-based paclitaxel in human SUM149 xenograft NOD SCID mouse model in adjuvant treatment. More important, we demonstrated that abraxane eliminates cancer stem cells in xenograft NOD SCID mouse model in advanced treatment, while solvent-based paclitaxel increases cancer stem cells. Cell uptake assay indicated that TNBC cells take more abraxane than solvent-based paclitaxel, which partially attributes to its superior efficacy in xenograft mouse models. Taken together, our data confirmed that abraxane is superior to solvent-based paclitaxel and may be a better option for TNBC patients in adjuvant or metastatic treatment. Citation Format: Hebao Yuan, Hongwei Guo, Feng Li, Joseph Burnett, Miao He, Nathan Truchan, Ila Myers, Duxin Sun. Abraxane eliminates cancer stem cells in triple-negative breast cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4788. doi:10.1158/1538-7445.AM2017-4788

Nanoparticle abraxane possesses impaired proliferation in A549 cells due to the underexpression of glucosamine 6-phosphate N-acetyltransferase 1 (GNPNAT1/GNA1).

Abraxane (Abr), a US Food and Drug Administration-approved albumin-bound nanoparticle applied for the treatment of non-small-cell lung cancer, has been reported to be more effective than paclitaxel (PTX). To further understand the molecular mechanisms that produce this superior drug efficacy of Abr, a quantitative proteomic approach has been applied to investigate the global protein expression profiles of lung cancer cell A549 treated with Abr and PTX. Only one protein, namely, glucosamine 6-phosphate N-acetyltransferase 1 (GNA1), showed significant differential expression (P<0.05) in the cutoff of 2.0 fold, suggesting that Abr can be used safely as a substitute for PTX. GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. Albumin plays a major role in the regulation of this protein. In summary, this study first shows that the superior drug effect of Abr is mainly due to the downregulation of GNA1, which causes proliferative delay and cell adhesion defect. It is also noteworthy that the deficiency of GNA1 might reduce insulin secretion which correlates with type 2 diabetes.

Co-delivery of all-trans-retinoic acid enhances the anti-metastasis effect of albumin-bound paclitaxel nanoparticles.

Co-delivery of all-trans-retinoic acid and paclitaxel using albumin-bound nanoparticles demonstrated a significantly improved anti-metastatic effect to breast cancer both in vitro and in vivo. Notably, the co-delivery nanoparticles exhibited more pronounced therapeutic effects than the combination of two free drugs or two HSA loaded single drugs.

Metastatic Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline.

To provide evidence-based recommendations to oncologists and others for the treatment of patients with metastatic pancreatic cancer. American Society of Clinical Oncology convened an Expert Panel of medical oncology, radiation oncology, surgical oncology, gastroenterology, palliative care, and advocacy experts to conduct a systematic review of the literature from April 2004 to June 2015. Outcomes were overall survival, disease-free survival, progression-free survival, and adverse events. Twenty-four randomized controlled trials met the systematic review criteria. A multiphase computed tomography scan of the chest, abdomen, and pelvis should be performed. Baseline performance status and comorbidity profile should be evaluated. Goals of care, patient preferences, treatment response, psychological status, support systems, and symptom burden should guide decisions for treatments. A palliative care referral should occur at first visit. FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin; favorable comorbidity profile) or gemcitabine plus nanoparticle albumin-bound (NAB) -paclitaxel (adequate comorbidity profile) should be offered to patients with Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 1 based on patient preference and support system available. Gemcitabine alone is recommended for patients with ECOG PS 2 or with a comorbidity profile that precludes other regimens; the addition of capecitabine or erlotinib may be offered. Patients with an ECOG PS ≥ 3 and poorly controlled comorbid conditions should be offered cancer-directed therapy only on a case-by-case basis; supportive care should be emphasized. For second-line therapy, gemcitabine plus NAB-paclitaxel should be offered to patients with first-line treatment with FOLFIRINOX, an ECOG PS 0 to 1, and a favorable comorbidity profile; fluorouracil plus oxaliplatin, irinotecan, or nanoliposomal irinotecan should be offered to patients with first-line treatment with gemcitabine plus NAB-paclitaxel, ECOG PS 0 to 1, and favorable comorbidity profile, and gemcitabine or fluorouracil should be offered to patients with either an ECOG PS 2 or a comorbidity profile that precludes other regimens. Additional information is available at www.asco.org/guidelines/MetPC and www.asco.org/guidelineswiki.

Nab-Paclitaxel in Metastatic Breast Cancer: Defining the Best Patient Profile.

Around 40% of patients with breast cancer will present with a recurrence of the disease. Chemotherapy is recommended for patients with recurrent hormone-independent or hormone-refractory breast cancer and almost all patients with metastatic breast cancer (MBC) receive chemotherapy during their medical history. Nanoparticle albuminbound (nab)-paclitaxel is a solvent-free, 130-nanometer particle formulation of paclitaxel. Nab-paclitaxel can be administered to all patients for whom the treatment choice is a taxane. In this review, 6 patient profiles for which nabpaclitaxel may be particularly useful are described and analyzed: (i) as first-line treatment of MBC, (ii) as second-line treatment of MBC after oral chemotherapy, (iii) after a standard taxane, (iv) as third-line treatment after a standard taxane and oral chemotherapy, (v) for patients with HER2-positive MBC and (vi) for patients with intolerance to standard taxanes. Nab-paclitaxel is a rational treatment choice for patients with MBC in different settings, as well as for those with prior exposure to a standard taxane.

The role of exosomes in promoting acquired resistance to gemcitabine and nanoparticle albumin-bound (NAB) paclitaxel in pancreatic ductal adenocarcinoma cells.

e23253Background: Acquired resistance to available chemotherapy is a major cause of treatment failure and poor prognosis in pancreatic ductal adenocarcinoma (PDAC). Exosomes, small (50-150 nm) secr...

ETNA (Evaluating Treatment with Neoadjuvant Abraxane) randomized phase III study comparing neoadjuvant nab-paclitaxel (nab-P) versus paclitaxel (P) both followed by anthracycline regimens in women with HER2-negative high-risk breast cancer: A MICHELANGO study.

502Background: Neoadjuvant chemotherapy regimens employing anthracyclines and taxanes have reported essentially doubled pCR rates with the addition of a taxane after anthracycline combinations. A reverse sequence did not reduce activity. nab-Paclitaxel (nab-P) is an albumin-bound nanoparticle of paclitaxel (P) that allows for safe infusion without premedication, and led to a significantly higher rate of pCR in the GeparSepto trial (Untch et al, Lancet Oncol 2016). Methods: This multicenter open label study (NCT01822314) in collaboration with GEICAM and BCRC-WA randomized 695 patients with centrally-confirmed HER2-negative breast cancer to P 90 mg/m2 (349 patients) or nab-P 125 mg/m2(346 patients). The two drugs were given on weeks 1, 2 and 3 followed by 1-week rest for 4 cycles before 4 cycles of an anthracycline regimen per investigator choice. Results: The ITT analysis of the primary endpoint pCR (absence of invasive cells in breast and nodes) along with the overall objective clinical response after sys...

Safety and efficacy of salvage nano-particle albumin bound paclitaxel in recurrent cervical cancer: a feasibility study.

BackgroundAfter platinum and taxane chemotherapy, with or without bevacizumab, active regimens for advanced or recurrent cervical cancer are lacking. Our objective was to review a single institution experience in treating recurrent, refractory cervical cancer with nano-particle albumin bound (NAB) paclitaxel with or without bevacizumab.MethodsThis retrospective case series was conducted in accordance with the regulations set forth by the Institutional Review Board at St. Joseph’s Hospital and Medical center. The chemotherapy log at the outpatient infusion center at the University of Arizona Cancer Center was reviewed to identify all advanced cervical cancer patients treated with NAB-paclitaxel from November 2011 until February 2015. The following data points were extracted from patient charts: demographic information, number of cycles, progression free survival (PFS), overall survival (OS), dose reductions and dose-limiting toxicities. In addition the average number of treatment cycles and age at recurrence were calculated.ResultsA total of 12 subjects were identified as receiving treatment with NAB-paclitaxel. Mean age at time of recurrence was 47.2 years (36–55). Nine subjects had squamous cell histology and three subjects had adenocarcinoma histology. All subjects had failed treatment with platinum and taxane, or platinum and topotecan chemotherapy. Two subjects were lost to follow up. The Median number of cycles of NAB-paclitaxel was 6.5 (2–19). The total number of cycles of NAB-paclitaxel in the study population was 65. Seven subjects were treated in combination with bevacizumab. Of these, three subjects are still alive and one subject is currently receiving active treatment with NAB-paclitaxel. The median PFS and OS for all subjects that met mortality endpoint was 4.8 months and 8.9 months (n = 7), respectively. One subject discontinued NAB-paclitaxel secondary to peripheral neuropathy, and one subject developed a vesicovaginal fistula while obtaining combination NAB-paclitaxel and bevacizumab therapy.ConclusionsNAB-paclitaxel with or without bevacizumab is tolerable and potentially active in treating recurrent cervical cancer after failing platinum-taxane or topotecan chemotherapy. This small case series deserves confirmation through prospective clinical trials.

Safety and efficacy of salvage nano-particle albumin bound paclitaxel in recurrent cervical cancer: A feasibility study

After platinum and taxane chemotherapy, with or without bevacizumab, active regimens for advanced or recurrent cervical cancer are lacking. Our objective was to review a single institution experience in treating recurrent, refractory cervical cancer with nano-particle albumin bound (NAB) paclitaxel with or without bevacizumab. This retrospective case series was conducted in accordance with the regulations set forth by the Institutional Review Board at St. Joseph’s Hospital and Medical center. The chemotherapy log at the outpatient infusion center at the University of Arizona Cancer Center was reviewed to identify all advanced cervical cancer patients treated with NAB-paclitaxel from November 2011 until February 2015. The following data points were extracted from patient charts: demographic information, number of cycles, progression free survival (PFS), overall survival (OS), dose reductions and dose-limiting toxicities. In addition the average number of treatment cycles and age at recurrence were calculated. A total of 12 subjects were identified as receiving treatment with NAB-paclitaxel. Mean age at time of recurrence was 47.2 years (36–55). Nine subjects had squamous cell histology and three subjects had adenocarcinoma histology. All subjects had failed treatment with platinum and taxane, or platinum and topotecan chemotherapy. Two subjects were lost to follow up. The Median number of cycles of NAB-paclitaxel was 6.5 (2–19). The total number of cycles of NAB-paclitaxel in the study population was 65. Seven subjects were treated in combination with bevacizumab. Of these, three subjects are still alive and one subject is currently receiving active treatment with NAB-paclitaxel. The median PFS and OS for all subjects that met mortality endpoint was 4.8 months and 8.9 months (n = 7), respectively. One subject discontinued NAB-paclitaxel secondary to peripheral neuropathy, and one subject developed a vesicovaginal fistula while obtaining combination NAB-paclitaxel and bevacizumab therapy. NAB-paclitaxel with or without bevacizumab is tolerable and potentially active in treating recurrent cervical cancer after failing platinum-taxane or topotecan chemotherapy. This small case series deserves confirmation through prospective clinical trials.

Quantitative Proteomic Analysis of Cellular Resistance to the Nanoparticle Abraxane.

Abraxane, an FDA-approved albumin-bound nanoparticle (NP) form of paclitaxel (PTX) to treat breast cancer and nonsmall cell lung cancer (NSCLC), has been demonstrated to be more effective than the original Taxol, the single molecule form. We have established a cell line from NSCLC A549 cells to be resistant to Abraxane. To further understand the molecular mechanisms involved in the NP drug resistance, global protein expression profiles of Abraxane sensitive (A549) and resistant cells (A549/Abr), along with the treatment of Abraxane, have been obtained by a quantitative proteomic approach. The most significantly differentially expressed proteins are associated with lipid metabolism, cell cycle, cytoskeleton, apoptosis pathways and processes, suggesting several mechanisms are working synergistically in A549 Abraxane-resistant cells. Overexpression of proteins in the lipid metabolism processes, such as E3 ubiquitin-protein ligase RNF139 (RNF139) and Hydroxymethylglutaryl-CoA synthase (HMGCS1), have not been reported previously in the study of paclitaxel resistance, suggesting possibly different mechanism between nanoparticle and single molecular drug resistance. In particular, RNF139 is one of the most up-regulated proteins in A549 Abraxane-resistant cell line, but remains no change when the resistant cells were further treated with Abraxane and down-regulated in the sensitive cells after 4 h treatment of Abraxane. This study shows the use of a proteomic strategy to understand the unique response of drug resistant cells to a nanoparticle therapeutic.

Industry Update

The month of May 2014 brought the news that AstraZeneca had rejected Pfizer's last and final offer to take over the company, while Valeant's attempts to acquire Allergan continued (both topics are covered in detail in last month's edition of Therapeutic Delivery). Companies that did agree to work together in May, at least in the form of licensing and collaboration agreements, included Avalanche and Regeneron (gene therapy via an adeno-associated virus-based delivery system), AADi and Celgene (in-licensing of sirolimus or rapamycin, formulated as albumin-bound nanoparticles), AntiOp and Reckitt Benckiser (nasal naloxone), Bristol-Myers Squibb and CytomX (Probody™ antibodies against immuno-oncology targets) and PolyTherics and Alpha Cancer Technologies (novel drug conjugates of alpha-fetoprotein). May also brought good news for Veloxis in the form of a positive opinion from the Committee for Medicinal Products for Human Use for its MeltDose® formulation of tacrolimus, and for RXi Pharmaceuticals which received a Notice of Allowance from the United States Patent and Trademark Office on a key patent for its self-delivering RNAi technology.

DI-090 Off-label drug prescriptions in hospital

BackgroundSpanish laws include the special availability situation of drugs that can be used for ‘off label’ indications. Off-label use is regulated by the RD 1015/2009 from 19th June law.PurposeTo study...

Albumin-bound nanoparticles of practically water-insoluble antimalarial lead greatly enhance its efficacy

We recently showed that the indolone-N-oxides can be promising candidates for the treatment of chloroquine-resistant malaria. However, the in vivo assays have been hampered by the very poor aqueous solubility of these compounds resulting in poor and variable activity. Here, we describe the preparation, characterization and in vivo evaluation of biodegradable albumin-bound indolone-N-oxide nanoparticles. Nanoparticles were prepared by precipitation followed by high-pressure homogenization and characterized by photon correlation spectroscopy, transmission electron microscopy, differential scanning calorimetry and X-ray powder diffraction. The process was optimized to yield nanoparticles of controllable diameter with narrow size distribution suitable for intravenous administration, which guarantees direct drug contact with parasitized erythrocytes. Stable nanoparticles showed greatly enhanced dissolution rate (complete drug release within 30 min compared to 1.5% of pure drug) preserving the rapid antimalarial activity. The formulation achieved complete cure of Plasmodium berghei-infected mice at 25mg/kg with parasitemia inhibition (99.1%) comparable to that of artesunate and chloroquine and was remarkably more effective in prolonging survival time and inhibiting recrudescence. In 'humanized' mice infected with Plasmodium falciparum, the same dose proved to be highly effective: with parasitemia reduced by 97.5% and the mean survival time prolonged. This formulation can help advance the preclinical trials of indolone-N-oxides. Albumin-bound nanoparticles represent a new strategic approach to use this most abundant plasma protein to target malaria-infected erythrocytes.

Extreme response to nab-paclitaxel and trastuzumab treatment in two patients with locally advanced or recurrent breast cancer

Nab-paclitaxel is a novel nanoparticle, albumin-bound paclitaxel that is free of solvents. The absence of solvents allows nab-paclitaxel to be administered without the premedication used routinely for the prevention of hypersensitivity reaction. In addition, the albumin-bound nanoparticle was designed to preferentially deliver paclitaxel to tumors by biologically interacting with albumin receptors that mediate drug transport. We report two cases of locally advanced or recurrent breast cancer patients with extreme response to nab-paclitaxel and trastuzumab treatment. One case is a 38-year-old woman who developed locally recurrent breast cancer, in her right chest wall; it was refractory to anthracycline and taxane treatment, and she had hypersensitivity to alcohol. After 6 cycles of chemotherapy with nab-paclitaxel (260 mg/m2) and trastuzumab every 3 weeks (q3w), the response to the treatment was clinical complete response (CR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, all recurrence masses seemed to have disappeared clinically, and pathological findings revealed that a slightly invasive lesion, measuring only 9 × 2 mm, remained. The second case is a 41-year-old woman with locally advanced breast cancer, whose tumor did not respond to chemotherapy with fluorouracil (500 mg/m2), epirubicin (100 mg/m2), and cyclophosphamide (500 mg/m2). She had active bronchial asthma. As second-line treatment, we used q3w nab-paclitaxel and trastuzumab. In spite of dose reduction for grade 2 liver dysfunction, she achieved pathological CR. Because our findings demonstrated remarkable efficacy and a good safety profile, we consider nab-paclitaxel with trastuzumab treatment to be one of the promising choices for locally advanced or recurrent breast cancer patients.

Abstract 5666: Albumin and paclitaxel co-localize in endocytic vesicles in HUVEC cells, and uptake is blocked by Cremophor EL.

Abstract Nab®-paclitaxel is an albumin-bound nanoparticle formulation of paclitaxel (ptx) that does not contain Cremophor EL (CrEL), and results in higher drug levels in xenografts and increased clinical activity in breast and lung cancers compared to ptx formulated with CrEL (Taxol®). Above the critical micellar concentration of 0.009%, CrEL forms long-lived micelles in circulation that can sequester ptx (peak plasma concentration in clinical use is 0.3%). Previous studies have shown CrEL reduces ptx binding to albumin, and Taxol® has reduced association with, and transport across endothelial cells compared to nab®-ptx (Desai, CCR 2006). Endothelial cells take up albumin, which is trafficked into recycling or transcytosis pathways or into lysosomes for degradation. Here, we explore mechanisms of uptake and trafficking of albumin and ptx in endothelial cells and the effect of CrEL on these events. Using fluorescence microscopy, we visualized the uptake of rhodamine-albumin and fluorescent ptx (Flutax). Albumin was present in EEA1-positive early endosomes and LAMP1-positive lysosomes. Notably, ptx was also present in vesicular structures and was often co-localized with albumin. The uptake of albumin was blocked by increasing concentrations (0.003%-0.3%) of CrEL, and also by inhibitors of caveolin-mediated endocytosis including indomethacin (blocks internalization of caveolae) and methyl-β-cyclodextrin (prevents formation of lipid rafts). The effect of CrEL on paclitaxel and albumin cellular uptake was confirmed by flow cytometry studies. 0.3% CrEL reduced the uptake of Flutax in DMSO, Flutax-modified nab®-ptx, and FITC-labeled albumin to close to background levels in both HUVEC and PC3 cells. Thus, in addition to its drug sequestration activity, CrEL directly affects endocytosis. We further evaluated CrEL effects on Flutax and ptx transport across endothelial monolayers in transwell chambers using a fluorescence detection assay. Two-fold more ptx crossed monolayers exposed to Flutax-containing nab®-ptx as compared to Taxol®. The effects of 0.001% to 0.3% CrEL on ptx transport at varying timepoints were investigated by mass spectrometry. Dose-dependent inhibition was observed, with a 3-fold reduction in transported ptx at 24 hrs. In summary, we have demonstrated that ptx co-localizes with albumin in endothelial cells, suggesting that the nab-ptx complex can remain intact within cells. Furthermore, CrEL interferes with albumin uptake at clinically relevant concentrations, thereby affecting paclitaxel cellular uptake and transport. These mechanistic studies further elucidate the basis of increased delivery of drug into the target cells by the nab®-ptx formulation as compared to Taxol®. Citation Format: Xiping Liu, Carrie Brachmann, Sean Hong, Shijuan Wu, Zeen Tong, Tapas De, Willard Foss, Gondi Kumar, Sekhar Surapaneni, Rajesh Chopra, Daniel Pierce, Carla Heise. Albumin and paclitaxel co-localize in endocytic vesicles in HUVEC cells, and uptake is blocked by Cremophor EL. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5666. doi:10.1158/1538-7445.AM2013-5666

Studies on lactoferrin nanoparticles of gambogic acid for oral delivery

Purpose: Lactoferrin (Lf), a mammalian cationic iron-binding glycoprotein belonging to the transferrin (Tf) family, has been widely used in a variety of fields ranging from treating infant diarrhea and supporting newborn growth to food and pharmaceutical applications. In this study, Lf nanoparticles were firstly used as carriers of gambogic acid (GA) to enhance oral absorption and anti-cancer activity, hence reducing the related toxic effect.Methods: Gambogic acid-lactoferrin nanoparticles (GL-NPs) were prepared by the nanoparticle albumin-bound (NAB) technology. The formed nanoparticles were characterized by DSC, TEM, etc. In situ intestinal perfusion experiment was performed to clarify the absorption mechanism of GL-NPs. Furthermore in vivo and in vitro anti-tumor activities of GL-NPs were also investigated.Results: GL-NPs was successfully prepared with about 150 nm mean size, +20 mV ζ potential, 92.3 ± 7.2% encapsulation efficiency and 9.04 ± 0.7% DL; GL-NPs also exhibited a better stability and a desirable slow release in vitro experiment. The results of in situ intestinal perfusion showed a transformation of GA absorption from passive diffusion into active transport or facilitated diffusion by GL-NPs. MTT assay of GL-NPs showed almost an equal anti-proliferative effect with arginine solution of GA (Arg-GA) in HepG2 cell. The inhibitory rate against S180 tumor mice after oral administration of GL-NPs was up to 86.01% which was1.39-folds of intravenous injection of Arg-GA.Conclusion: The in vitro results showed that the NAB technology was feasible for industrial production of Lf nanoparticles and the in vivo results proved that the effective GL-NPs is a promising approach for the oral delivery of GA. These obtained research works have also paved the preliminary way for the study of Lf as an oral drug delivery carrier.

Paclitaxel Nano-Delivery Systems: A Comprehensive Review

Paclitaxel is one of the most effective chemotherapeutic drugs ever developed and is active against a broad range of cancers, such as lung, ovarian, and breast cancers. Due to its low water solubility, paclitaxel is formulated in a mixture of Cremophor EL and dehydrated ethanol (50:50, v/v) a combination known as Taxol. However, Taxol has some severe side effects related to Cremophor EL and ethanol. Therefore, there is an urgent need for the development of alternative Taxol formulations. The encapsulation of paclitaxel in biodegradable and non-toxic nano-delivery systems can protect the drug from degradation during circulation and in-turn protect the body from toxic side effects of the drug thereby lowering its toxicity, increasing its circulation half-life, exhibiting improved pharmacokinetic profiles, and demonstrating better patient compliance. Also, nanoparticle-based delivery systems can take advantage of the enhanced permeability and retention (EPR) effect for passive tumor targeting, therefore, they are promising carriers to improve the therapeutic index and decrease the side effects of paclitaxel. To date, paclitaxel albumin-bound nanoparticles (Abraxane®) have been approved by the FDA for the treatment of metastatic breast cancer and non-small cell lung cancer (NSCLC). In addition, there are a number of novel paclitaxel nanoparticle formulations in clinical trials. In this comprehensive review, several types of developed paclitaxel nano-delivery systems will be covered and discussed, such as polymeric nanoparticles, lipid-based formulations, polymer conjugates, inorganic nanoparticles, carbon nanotubes, nanocrystals, and cyclodextrin nanoparticles.

Topical dorzolamide therapy for taxane-related macular oedema

Sir, The taxane class of drugs (eg, paclitaxel (Taxol), paclitaxel nanoparticle albumin bound (NAB) (Abraxane), docetaxel (Taxotere)) are microtubule-stabilizing agents that are used to treat numerous malignancies. Cystoid macular oedema (CME) without increased permeability is a rare side effect of these medications.1, 2, 3 In the following report, non-leaking CME secondary to paclitaxel–NAB was successfully treated with off-label use of topical 2% dorzolamide (Trusopt) in conjunction with cessation of the chemotherapy agent. A monocular treatment trial suggested more rapid resolution with dorzolamide compared with drug cessation alone.

Cytotoxicity of nab-paclitaxel and SPARC expression in ovarian cell lines: An in vitro and in vivo study.

e13529 Background: Nab-paclitaxel (NP) is a solvent-free, albumin-bound nanoparticle formulation; it binds to albumin receptor on endothelial cells, which in turn activates caveolin-1. Lack of solv...