Hexadecylphosphocholine, a new Antineoplastic Agent: Cytotoxic properties in leukaemic cells

Eibl, H.; Unger, Clemens; Fleer, E. A. M.; Kim, D. J.; Berger, M R; Nagel, G. A.

doi:10.1007/bf02579867

Cited by 11 publications

(4 citation statements)

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“…26 Increased cytotoxicity of OA and MFS-containing LNCs can be attributed to cytotoxic effects reported on different cell lines. [60][61][62] PZQ-LNCs showed similar cytotoxicity to the corresponding blank formulations, supporting data for PZQ thermosensitive nanoemulsion. 36 Importantly, PZQ-LNC formulations showed better tolerability compared to free PZQ, an observation reported for PZQ solid lipid NPs.…”

Section: Discussionsupporting

confidence: 73%

Praziquantel–lipid nanocapsules: an oral nanotherapeutic with potential <em>Schistosoma mansoni</em> tegumental targeting

Amara¹,

Ramadan²,

El‐Moslemany³

et al. 2018

IJN

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PurposeLipid nanocapsules (LNCs) have shown potential to increase the bioavailability and efficacy of orally administered drugs. However, their intestinal translocation to distal target sites and their implication in pharmacokinetic (PK)–pharmacodynamic (PD) relationships are yet to be elucidated. In this study, the effect of LNCs on the PD activity and pharmacokinetics of praziquantel (PZQ), the mainstay of schistosomiasis chemotherapy, was investigated.Materials and methodsThe composition of LNCs was modified to increase PZQ payload and to enhance membrane permeability. PZQ–LNCs were characterized in vitro for colloidal properties, entrapment efficiency (EE%), and drug release. PD activity of the test formulations was assessed in Schistosoma mansoni-infected mice 7 days post-oral administration of a single 250 mg/kg oral dose. Pharmacokinetics of the test formulations and their stability in simulated gastrointestinal (GI) fluids were investigated to substantiate in vivo data.ResultsPZQ–LNCs exhibited good pharmaceutical attributes in terms of size (46–62 nm), polydispersity index (0.01–0.08), EE% (>95%), and sustained release profiles. Results indicated significant efficacy enhancement by reduction in worm burden, amelioration of liver pathology, and extensive damage to the fluke suckers and tegument. This was partly explained by PK data determined in rats. In addition, oral targeting of the worms was supported by the stability of PZQ–LNCs in simulated GI fluids and scanning electron microscopy (SEM) visualization of nanostructures on the tegument of worms recovered from mesenteric/hepatic veins. Cytotoxicity data indicated tolerability of PZQ–LNCs.ConclusionData obtained provide evidence for the ability of oral LNCs to target distal post-absorption sites, leading to enhanced drug efficacy. From a practical standpoint, PZQ–LNCs could be suggested as a potential tolerable single lower dose oral nanomedicine for more effective PZQ mass chemotherapy.

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Section: Discussionsupporting

confidence: 73%

Praziquantel–lipid nanocapsules: an oral nanotherapeutic with potential <em>Schistosoma mansoni</em> tegumental targeting

Amara¹,

Ramadan²,

El‐Moslemany³

et al. 2018

IJN

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“…Ulceration was most likely linked to progression of the malignant disease. [1,2,7], In the clinical management of skin metastases and local recurren ces in breast cancer patients, topical application of a cytotoxic drug may provide an effective, tolerable and safe treatment approach. Miltefosine showed pronounced in vivo antitumor activity in rat mammary carcinomas [3,4] and, due to its am phiphilic behavior, it seemed to be a promising candidate for topical treatment in breast cancer patients.…”

Section: Resultsmentioning

confidence: 99%

Topically Applied Miltefosine (Hexadecylphosphocholine) in Patients with Skin-Metastasized Breast Cancer. A Phase II Study

linger¹,

Herrmann²,

Berdel³

et al. 1993

Oncol Res Treat

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Background: A clinical phase II study with a topical formulation of hexadecylphosphocholine (Miltefosine solution 6%) was performed in patients with skin-metas-tasized or locally recurrent breast cancer. Material and Methods: 76 patients had entered the study. At study entry, skin metas-tases or local recurrences were progressive, newly diagnosed or recurrent in most cases and stable in a few. All patients were pretreated with up to 4 different standard treatment modalities (surgery, radio-, chemo- and endocrine therapy). 24/76 patients had to be excluded from response analysis due to changes in the systemic anticancer therapy prior to study entry or during the study period (12/24), due to early systemic tumor progression (5/24), refusal of treatment (2/24), insufficient documentation (3/24), male breast cancer (1/24), or performance status of WHO grade 3 at study entry (1/24). Results: Within the scheduled time for response assessment (2 months) remissions were achieved in a total of 12 out of 52 patients (1 CR, 11 PR). In patients with concomitant systemic antitumor therapy the response rate was 24% (7/29), while it was 22% (5/23) in patients without concomitant systemic antitumor treatment. In 52% of the patients (27/52) a stabilization of the skin infiltration (no change) was observed. The treatment was well tolerated by the majority of patients. In 2/74 patients treatment was discontinued due to pruritus. In 46/74 patients local adverse reactions were observed, presenting as pruritus, rash, dry skin, bleeding at ulcer/lesion and skin atrophy. Systemic adverse reactions (anorexia, nausea/vomiting, alopecia, stomatitis) were only seen in patients with systemic antineoplastic comedication. Conclusion: This phase II trial confirms results of a phase I trial showing that topically applied Miltefosine solution causes objective tumor response in skin-metastasized and/or locally recurrent breast cancer.

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“…Miltefosine belongs to a new group of antitumoral active agents, the alkylphosphocholines, that were originally devel oped by Eibl and Unger [8,9], Preclinical studies with Miltefo sine showed distinct antiproliferative-cytotoxic activity in vitro [1,3,4,9], In vivo, orally applied Miltefosine causes complete tumor regression of chemically induced rat mammary carcino mas [2,3]. Furthermore, tumor cell differentiation was asso ciated with its in vivo therapeutic effects [3], Although it is widely accepted that the main target of Miltefosine is the plas ma membrane and not the cell nucleus, the exact mechanism of action for this new antitumor drug is still unknown.…”

Section: Discussionmentioning

confidence: 99%

Daily Oral Miltefosine (Hexadecylphosphocholine) in Patients with Advanced Breast Cancer: A Phase II Study

et al. 1993

Self Cite

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Background: A clinical phase II study with an oral formulation of Miltefosine (INN of hexadecylphosphocholine) was performed in patients with locally advanced or metastatic breast cancer. Material and Methods: Eligibility criteria included histological proof of breast cancer, measurable disease without previous radiotherapy of the indicator lesions, pretreatment with chemotherapy, WHO performance status of grade < 2, and informed consent. The drug was given twice daily at a single dose of 50 mg for the first week with the option of increasing the daily dose to 150 mg in the second week if tolerability was good. The minimum treatment duration was 9 weeks. Results: 23 patients have been entered into the study and 17 were evaluable for toxicity. 11 patients were evaluable for response. There was no objective tumor response. 4 out of 11 patients had reached a no-change status. Progressive disease was seen in 7 patients with 2 early deaths. Gastrointestinal side effects like nausea and vomiting (15/17) and loss of appetite (15/17) reached a maximum of WHO grade 4, diarrhea (4/17) was at the most of WHO grade 3. Conclusion: Miltefosine given daily by oral route showed no therapeutic activity in patients with advanced metastatic breast cancer.

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Hexadecylphosphocholine, a new Antineoplastic Agent: Cytotoxic properties in leukaemic cells

Cited by 11 publications

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Praziquantel–lipid nanocapsules: an oral nanotherapeutic with potential <em>Schistosoma mansoni</em> tegumental targeting

Praziquantel–lipid nanocapsules: an oral nanotherapeutic with potential <em>Schistosoma mansoni</em> tegumental targeting

Topically Applied Miltefosine (Hexadecylphosphocholine) in Patients with Skin-Metastasized Breast Cancer. A Phase II Study

Daily Oral Miltefosine (Hexadecylphosphocholine) in Patients with Advanced Breast Cancer: A Phase II Study

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Hexadecylphosphocholine, a new Antineoplastic Agent: Cytotoxic properties in leukaemic cells

Cited by 11 publications

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Praziquantel&ndash;lipid nanocapsules: an oral nanotherapeutic with potential <em>Schistosoma mansoni</em> tegumental targeting

Praziquantel&ndash;lipid nanocapsules: an oral nanotherapeutic with potential <em>Schistosoma mansoni</em> tegumental targeting

Topically Applied Miltefosine (Hexadecylphosphocholine) in Patients with Skin-Metastasized Breast Cancer. A Phase II Study

Daily Oral Miltefosine (Hexadecylphosphocholine) in Patients with Advanced Breast Cancer: A Phase II Study

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Product

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Praziquantel–lipid nanocapsules: an oral nanotherapeutic with potential <em>Schistosoma mansoni</em> tegumental targeting

Praziquantel–lipid nanocapsules: an oral nanotherapeutic with potential <em>Schistosoma mansoni</em> tegumental targeting