The hydroxypropyl‐β‐cyclodextrin‐minoxidil inclusion complex improves the cardiovascular and proliferative adverse effects of minoxidil in male rats: Implications in the treatment of alopecia
Abstract The efficacy of minoxidil (MXD) ethanolic solutions (1%‐5% w/v) in the treatment of androgenetic alopecia is limited by adverse reactions. The toxicological effects of repeated topical applications of escalating dose (0.035%‐3.5% w/v) and of single and twice daily doses (3.5% w/v) of a nove...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-06-01
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| Series: | Pharmacology Research & Perspectives |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/prp2.585 |
| _version_ | 1831751281893441536 |
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| author | Fatima Maqoud Nicola Zizzo Antonietta Mele Nunzio Denora Giuseppe Passantino Rosa Scala Annalisa Cutrignelli Antonella Tinelli Valentino Laquintana Flavia laForgia Sergio Fontana Massimo Franco Angela Assunta Lopedota Domenico Tricarico |
| author_facet | Fatima Maqoud Nicola Zizzo Antonietta Mele Nunzio Denora Giuseppe Passantino Rosa Scala Annalisa Cutrignelli Antonella Tinelli Valentino Laquintana Flavia laForgia Sergio Fontana Massimo Franco Angela Assunta Lopedota Domenico Tricarico |
| author_sort | Fatima Maqoud |
| collection | DOAJ |
| description | Abstract The efficacy of minoxidil (MXD) ethanolic solutions (1%‐5% w/v) in the treatment of androgenetic alopecia is limited by adverse reactions. The toxicological effects of repeated topical applications of escalating dose (0.035%‐3.5% w/v) and of single and twice daily doses (3.5% w/v) of a novel hydroxypropyl‐β‐cyclodextrin MXD GEL formulation (MXD/HP‐β‐CD) and a MXD solution were investigated in male rats. The cardiovascular effects were evaluated by telemetric monitoring of ECG and arterial pressure in free‐moving rats. Ultrasonographic evaluation of cardiac morphology and function, and histopathological and biochemical analysis of the tissues, were performed. A pharmacovigilance investigation was undertaken using the EudraVigilance database for the evaluation of the potential cancer‐related effects of topical MXD. Following the application of repeated escalating doses of MXD solution, cardiac hypertrophy, hypotension, enhanced serum natriuretic peptides and K+‐ion levels, serum liver biomarkers, and histological lesions including renal cancer were observed. In addition, the administration of a twice daily dose of MXD solution, at SF rat vs human = 311, caused reductions in the systolic, diastolic, and mean blood pressure of the rats (−30.76 ± 3%, −28.84 ± 4%, and −30.66 ± 5%, respectively, vs the baseline; t test P < .05). These effects were not reversible following washout of the MXD solution. Retrospective investigation showed 32 cases of cancer associated with the use of topical MXD in humans. The rats treated with MXD HP‐β‐CD were less severely affected. MXD causes proliferative adverse effects. The MXD HP‐β‐CD inclusion complex reduces these adverse effects. |
| first_indexed | 2024-12-21T22:42:11Z |
| format | Article |
| id | doaj.art-2b598d239ed24be79ab832f29cc8f374 |
| institution | Directory Open Access Journal |
| issn | 2052-1707 |
| language | English |
| last_indexed | 2024-12-21T22:42:11Z |
| publishDate | 2020-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pharmacology Research & Perspectives |
| spelling | doaj.art-2b598d239ed24be79ab832f29cc8f3742022-12-21T18:47:49ZengWileyPharmacology Research & Perspectives2052-17072020-06-0183n/an/a10.1002/prp2.585The hydroxypropyl‐β‐cyclodextrin‐minoxidil inclusion complex improves the cardiovascular and proliferative adverse effects of minoxidil in male rats: Implications in the treatment of alopeciaFatima Maqoud0Nicola Zizzo1Antonietta Mele2Nunzio Denora3Giuseppe Passantino4Rosa Scala5Annalisa Cutrignelli6Antonella Tinelli7Valentino Laquintana8Flavia laForgia9Sergio Fontana10Massimo Franco11Angela Assunta Lopedota12Domenico Tricarico13Section of Pharmacology Department of Pharmacy – Pharmaceutical Sciences University of Bari Bari ItalyAnatomy Pathology Department of Veterinary Medicine University of Bari Bari ItalySection of Pharmacology Department of Pharmacy – Pharmaceutical Sciences University of Bari Bari ItalyPharmaceutical Technology Department of Pharmacy – Pharmaceutical Sciences University of Bari Bari ItalyAnatomy Pathology Department of Veterinary Medicine University of Bari Bari ItalySection of Pharmacology Department of Pharmacy – Pharmaceutical Sciences University of Bari Bari ItalyPharmaceutical Technology Department of Pharmacy – Pharmaceutical Sciences University of Bari Bari ItalyAnatomy Pathology Department of Veterinary Medicine University of Bari Bari ItalyPharmaceutical Technology Department of Pharmacy – Pharmaceutical Sciences University of Bari Bari ItalyFarmalabor s.r.I. Centro di Ricerca “Dr. Sergio Fontana 1900‐1982” Canosa di Puglia ItalyFarmalabor s.r.I. Centro di Ricerca “Dr. Sergio Fontana 1900‐1982” Canosa di Puglia ItalyPharmaceutical Technology Department of Pharmacy – Pharmaceutical Sciences University of Bari Bari ItalyPharmaceutical Technology Department of Pharmacy – Pharmaceutical Sciences University of Bari Bari ItalySection of Pharmacology Department of Pharmacy – Pharmaceutical Sciences University of Bari Bari ItalyAbstract The efficacy of minoxidil (MXD) ethanolic solutions (1%‐5% w/v) in the treatment of androgenetic alopecia is limited by adverse reactions. The toxicological effects of repeated topical applications of escalating dose (0.035%‐3.5% w/v) and of single and twice daily doses (3.5% w/v) of a novel hydroxypropyl‐β‐cyclodextrin MXD GEL formulation (MXD/HP‐β‐CD) and a MXD solution were investigated in male rats. The cardiovascular effects were evaluated by telemetric monitoring of ECG and arterial pressure in free‐moving rats. Ultrasonographic evaluation of cardiac morphology and function, and histopathological and biochemical analysis of the tissues, were performed. A pharmacovigilance investigation was undertaken using the EudraVigilance database for the evaluation of the potential cancer‐related effects of topical MXD. Following the application of repeated escalating doses of MXD solution, cardiac hypertrophy, hypotension, enhanced serum natriuretic peptides and K+‐ion levels, serum liver biomarkers, and histological lesions including renal cancer were observed. In addition, the administration of a twice daily dose of MXD solution, at SF rat vs human = 311, caused reductions in the systolic, diastolic, and mean blood pressure of the rats (−30.76 ± 3%, −28.84 ± 4%, and −30.66 ± 5%, respectively, vs the baseline; t test P < .05). These effects were not reversible following washout of the MXD solution. Retrospective investigation showed 32 cases of cancer associated with the use of topical MXD in humans. The rats treated with MXD HP‐β‐CD were less severely affected. MXD causes proliferative adverse effects. The MXD HP‐β‐CD inclusion complex reduces these adverse effects.https://doi.org/10.1002/prp2.585androgenic alopeciaATP‐sensitive potassium channelscell proliferationminoxidiltoxicology |
| spellingShingle | Fatima Maqoud Nicola Zizzo Antonietta Mele Nunzio Denora Giuseppe Passantino Rosa Scala Annalisa Cutrignelli Antonella Tinelli Valentino Laquintana Flavia laForgia Sergio Fontana Massimo Franco Angela Assunta Lopedota Domenico Tricarico The hydroxypropyl‐β‐cyclodextrin‐minoxidil inclusion complex improves the cardiovascular and proliferative adverse effects of minoxidil in male rats: Implications in the treatment of alopecia Pharmacology Research & Perspectives androgenic alopecia ATP‐sensitive potassium channels cell proliferation minoxidil toxicology |
| title | The hydroxypropyl‐β‐cyclodextrin‐minoxidil inclusion complex improves the cardiovascular and proliferative adverse effects of minoxidil in male rats: Implications in the treatment of alopecia |
| title_full | The hydroxypropyl‐β‐cyclodextrin‐minoxidil inclusion complex improves the cardiovascular and proliferative adverse effects of minoxidil in male rats: Implications in the treatment of alopecia |
| title_fullStr | The hydroxypropyl‐β‐cyclodextrin‐minoxidil inclusion complex improves the cardiovascular and proliferative adverse effects of minoxidil in male rats: Implications in the treatment of alopecia |
| title_full_unstemmed | The hydroxypropyl‐β‐cyclodextrin‐minoxidil inclusion complex improves the cardiovascular and proliferative adverse effects of minoxidil in male rats: Implications in the treatment of alopecia |
| title_short | The hydroxypropyl‐β‐cyclodextrin‐minoxidil inclusion complex improves the cardiovascular and proliferative adverse effects of minoxidil in male rats: Implications in the treatment of alopecia |
| title_sort | hydroxypropyl β cyclodextrin minoxidil inclusion complex improves the cardiovascular and proliferative adverse effects of minoxidil in male rats implications in the treatment of alopecia |
| topic | androgenic alopecia ATP‐sensitive potassium channels cell proliferation minoxidil toxicology |
| url | https://doi.org/10.1002/prp2.585 |
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