Enhancing Oral Bioavailability and Brain Biodistribution of Perillyl Alcohol Using Nanostructured Lipid Carriers
Perillyl alcohol (POH), a bioactive monoterpenoid derived from limonene, shows promise as an antitumor agent for brain tumor treatment. However, its limited oral bioavailability and inadequate brain distribution hinder its efficacy. To address these challenges, this study developed nanostructured li...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-07-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/8/1055 |
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| author | Samila Horst Peczek Ana Paula Santos Tartari Isabella Camargo Zittlau Camila Diedrich Christiane Schineider Machado Rubiana Mara Mainardes |
| author_facet | Samila Horst Peczek Ana Paula Santos Tartari Isabella Camargo Zittlau Camila Diedrich Christiane Schineider Machado Rubiana Mara Mainardes |
| author_sort | Samila Horst Peczek |
| collection | DOAJ |
| description | Perillyl alcohol (POH), a bioactive monoterpenoid derived from limonene, shows promise as an antitumor agent for brain tumor treatment. However, its limited oral bioavailability and inadequate brain distribution hinder its efficacy. To address these challenges, this study developed nanostructured lipid carriers (NLCs) loaded with POH to improve its brain biodistribution. The NLCs prepared using hot homogenization exhibited an average diameter of 287 nm and a spherical morphology with a polydispersity index of 0.143. High encapsulation efficiency of 99.68% was achieved. X-ray diffraction analyses confirmed the semicrystalline state of POH-loaded NLCs. In vitro release studies demonstrated a biphasic release profile. Stability studies in simulated gastric and intestinal fluids confirmed their ability to withstand pH variations and digestive enzymes. In vivo pharmacokinetic studies in rats revealed significantly enhanced oral bioavailability of POH when encapsulated in the NLCs. Biodistribution studies showed increased POH concentration in brain tissue with NLCs compared with free POH, which was distributed more in non-target tissues such as the liver, lungs, kidneys, and spleen. These findings underscore the potential of NLCs as effective delivery systems for enhancing oral bioavailability and brain biodistribution of POH, providing a potential therapeutic strategy for brain tumor treatment. |
| first_indexed | 2024-03-10T23:39:50Z |
| format | Article |
| id | doaj.art-ae6489179e9f4550b007cbb93b4cc543 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T23:39:50Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-ae6489179e9f4550b007cbb93b4cc5432023-11-19T02:33:11ZengMDPI AGPharmaceuticals1424-82472023-07-01168105510.3390/ph16081055Enhancing Oral Bioavailability and Brain Biodistribution of Perillyl Alcohol Using Nanostructured Lipid CarriersSamila Horst Peczek0Ana Paula Santos Tartari1Isabella Camargo Zittlau2Camila Diedrich3Christiane Schineider Machado4Rubiana Mara Mainardes5Laboratory of Nanostructured Formulations, Universidade Estadual do Centro-Oeste, Alameda Élio Antonio Dalla Vecchia St., 838, Guarapuava 85040-167, PR, BrazilLaboratory of Nanostructured Formulations, Universidade Estadual do Centro-Oeste, Alameda Élio Antonio Dalla Vecchia St., 838, Guarapuava 85040-167, PR, BrazilLaboratory of Nanostructured Formulations, Universidade Estadual do Centro-Oeste, Alameda Élio Antonio Dalla Vecchia St., 838, Guarapuava 85040-167, PR, BrazilLaboratory of Nanostructured Formulations, Universidade Estadual do Centro-Oeste, Alameda Élio Antonio Dalla Vecchia St., 838, Guarapuava 85040-167, PR, BrazilLaboratory of Nanostructured Formulations, Universidade Estadual do Centro-Oeste, Alameda Élio Antonio Dalla Vecchia St., 838, Guarapuava 85040-167, PR, BrazilLaboratory of Nanostructured Formulations, Universidade Estadual do Centro-Oeste, Alameda Élio Antonio Dalla Vecchia St., 838, Guarapuava 85040-167, PR, BrazilPerillyl alcohol (POH), a bioactive monoterpenoid derived from limonene, shows promise as an antitumor agent for brain tumor treatment. However, its limited oral bioavailability and inadequate brain distribution hinder its efficacy. To address these challenges, this study developed nanostructured lipid carriers (NLCs) loaded with POH to improve its brain biodistribution. The NLCs prepared using hot homogenization exhibited an average diameter of 287 nm and a spherical morphology with a polydispersity index of 0.143. High encapsulation efficiency of 99.68% was achieved. X-ray diffraction analyses confirmed the semicrystalline state of POH-loaded NLCs. In vitro release studies demonstrated a biphasic release profile. Stability studies in simulated gastric and intestinal fluids confirmed their ability to withstand pH variations and digestive enzymes. In vivo pharmacokinetic studies in rats revealed significantly enhanced oral bioavailability of POH when encapsulated in the NLCs. Biodistribution studies showed increased POH concentration in brain tissue with NLCs compared with free POH, which was distributed more in non-target tissues such as the liver, lungs, kidneys, and spleen. These findings underscore the potential of NLCs as effective delivery systems for enhancing oral bioavailability and brain biodistribution of POH, providing a potential therapeutic strategy for brain tumor treatment.https://www.mdpi.com/1424-8247/16/8/1055lipid nanoparticlesperillyl acidpharmacokineticsbiodistribution |
| spellingShingle | Samila Horst Peczek Ana Paula Santos Tartari Isabella Camargo Zittlau Camila Diedrich Christiane Schineider Machado Rubiana Mara Mainardes Enhancing Oral Bioavailability and Brain Biodistribution of Perillyl Alcohol Using Nanostructured Lipid Carriers Pharmaceuticals lipid nanoparticles perillyl acid pharmacokinetics biodistribution |
| title | Enhancing Oral Bioavailability and Brain Biodistribution of Perillyl Alcohol Using Nanostructured Lipid Carriers |
| title_full | Enhancing Oral Bioavailability and Brain Biodistribution of Perillyl Alcohol Using Nanostructured Lipid Carriers |
| title_fullStr | Enhancing Oral Bioavailability and Brain Biodistribution of Perillyl Alcohol Using Nanostructured Lipid Carriers |
| title_full_unstemmed | Enhancing Oral Bioavailability and Brain Biodistribution of Perillyl Alcohol Using Nanostructured Lipid Carriers |
| title_short | Enhancing Oral Bioavailability and Brain Biodistribution of Perillyl Alcohol Using Nanostructured Lipid Carriers |
| title_sort | enhancing oral bioavailability and brain biodistribution of perillyl alcohol using nanostructured lipid carriers |
| topic | lipid nanoparticles perillyl acid pharmacokinetics biodistribution |
| url | https://www.mdpi.com/1424-8247/16/8/1055 |
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