Transdermal Delivery of α-Aminophosphonates as Semisolid Formulations—An In Vitro-Ex Vivo Study
α-Aminophosphonates are organophosphorus compounds with an obvious similarity with α-amino acids. Owing to their biological and pharmacological characteristics, they have attracted the attention of many medicinal chemists. α-Aminophosphonates are known to exhibit antiviral, antitumor, antimicrobial,...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/5/1464 |
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| author | Dorottya Kocsis Petra Regina Varga Rusul Keshwan Mina Nader Miléna Lengyel Pál Szabó István Antal Károly Kánai György Keglevich Franciska Erdő |
| author_facet | Dorottya Kocsis Petra Regina Varga Rusul Keshwan Mina Nader Miléna Lengyel Pál Szabó István Antal Károly Kánai György Keglevich Franciska Erdő |
| author_sort | Dorottya Kocsis |
| collection | DOAJ |
| description | α-Aminophosphonates are organophosphorus compounds with an obvious similarity with α-amino acids. Owing to their biological and pharmacological characteristics, they have attracted the attention of many medicinal chemists. α-Aminophosphonates are known to exhibit antiviral, antitumor, antimicrobial, antioxidant and antibacterial activities, which can all be important in pathological dermatological conditions. However, their ADMET properties are not well studied. The aim of the current study was to provide preliminary information about the skin penetration of three preselected α-aminophosphonates when applying them as topical cream formulations in static and dynamic diffusion chambers. The results indicate that aminophosphonate <b>1a</b>, without any substituent in the para position, shows the best release from the formulation and the highest absorption through the excised skin. However, based on our previous study, the in vitro pharmacological potency was higher in the case of para-substituted molecules <b>1b</b> and <b>1c</b>. The particle size and rheological studies revealed that the 2% cream of aminophosphonate <b>1a</b> was the most homogenous formulation. In conclusion, the most promising molecule was <b>1a</b>, but further experiments are proposed to uncover the possible transporter interactions in the skin, optimize the topical formulations and improve PK/PD profiles in case of transdermal delivery. |
| first_indexed | 2024-03-11T03:24:09Z |
| format | Article |
| id | doaj.art-2d31ee8581e2479d9482d5fdc4bf1aac |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T03:24:09Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-2d31ee8581e2479d9482d5fdc4bf1aac2023-11-18T02:51:57ZengMDPI AGPharmaceutics1999-49232023-05-01155146410.3390/pharmaceutics15051464Transdermal Delivery of α-Aminophosphonates as Semisolid Formulations—An In Vitro-Ex Vivo StudyDorottya Kocsis0Petra Regina Varga1Rusul Keshwan2Mina Nader3Miléna Lengyel4Pál Szabó5István Antal6Károly Kánai7György Keglevich8Franciska Erdő9Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Práter u. 50a, H-1083 Budapest, HungaryDepartment of Organic Chemistry and Technology, Budapest University of Technology and Economics, H-1521 Budapest, HungaryFaculty of Information Technology and Bionics, Pázmány Péter Catholic University, Práter u. 50a, H-1083 Budapest, HungaryFaculty of Information Technology and Bionics, Pázmány Péter Catholic University, Práter u. 50a, H-1083 Budapest, HungaryDepartment of Pharmaceutics, Semmelweis University, H-1092 Budapest, HungaryCentre for Structural Study, Research Centre for Natural Sciences, H-1117 Budapest, HungaryDepartment of Pharmaceutics, Semmelweis University, H-1092 Budapest, HungaryDepartment of Organic Chemistry and Technology, Budapest University of Technology and Economics, H-1521 Budapest, HungaryDepartment of Organic Chemistry and Technology, Budapest University of Technology and Economics, H-1521 Budapest, HungaryFaculty of Information Technology and Bionics, Pázmány Péter Catholic University, Práter u. 50a, H-1083 Budapest, Hungaryα-Aminophosphonates are organophosphorus compounds with an obvious similarity with α-amino acids. Owing to their biological and pharmacological characteristics, they have attracted the attention of many medicinal chemists. α-Aminophosphonates are known to exhibit antiviral, antitumor, antimicrobial, antioxidant and antibacterial activities, which can all be important in pathological dermatological conditions. However, their ADMET properties are not well studied. The aim of the current study was to provide preliminary information about the skin penetration of three preselected α-aminophosphonates when applying them as topical cream formulations in static and dynamic diffusion chambers. The results indicate that aminophosphonate <b>1a</b>, without any substituent in the para position, shows the best release from the formulation and the highest absorption through the excised skin. However, based on our previous study, the in vitro pharmacological potency was higher in the case of para-substituted molecules <b>1b</b> and <b>1c</b>. The particle size and rheological studies revealed that the 2% cream of aminophosphonate <b>1a</b> was the most homogenous formulation. In conclusion, the most promising molecule was <b>1a</b>, but further experiments are proposed to uncover the possible transporter interactions in the skin, optimize the topical formulations and improve PK/PD profiles in case of transdermal delivery.https://www.mdpi.com/1999-4923/15/5/1464α-aminophosphonatestransdermal penetrationtopical formulationskin-on-a-chiprheologydroplet size distribution |
| spellingShingle | Dorottya Kocsis Petra Regina Varga Rusul Keshwan Mina Nader Miléna Lengyel Pál Szabó István Antal Károly Kánai György Keglevich Franciska Erdő Transdermal Delivery of α-Aminophosphonates as Semisolid Formulations—An In Vitro-Ex Vivo Study Pharmaceutics α-aminophosphonates transdermal penetration topical formulation skin-on-a-chip rheology droplet size distribution |
| title | Transdermal Delivery of α-Aminophosphonates as Semisolid Formulations—An In Vitro-Ex Vivo Study |
| title_full | Transdermal Delivery of α-Aminophosphonates as Semisolid Formulations—An In Vitro-Ex Vivo Study |
| title_fullStr | Transdermal Delivery of α-Aminophosphonates as Semisolid Formulations—An In Vitro-Ex Vivo Study |
| title_full_unstemmed | Transdermal Delivery of α-Aminophosphonates as Semisolid Formulations—An In Vitro-Ex Vivo Study |
| title_short | Transdermal Delivery of α-Aminophosphonates as Semisolid Formulations—An In Vitro-Ex Vivo Study |
| title_sort | transdermal delivery of α aminophosphonates as semisolid formulations an in vitro ex vivo study |
| topic | α-aminophosphonates transdermal penetration topical formulation skin-on-a-chip rheology droplet size distribution |
| url | https://www.mdpi.com/1999-4923/15/5/1464 |
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