Physicochemical Characterizations and Pharmacokinetic Evaluation of Pentazocine Solid Lipid Nanoparticles against Inflammatory Pain Model
Pentazocine (PTZ), a narcotic-antagonist analgesic, has been extensively used in the treatment of initial carcinogenic or postoperative pain. Hepatic first-pass metabolism results in low oral bioavailability and high dose wastage. Herein, 10 mg (-)-Pentazocine (HPLC-grade) was incorporated to solid...
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| Format: | Article |
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MDPI AG
2022-02-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/2/409 |
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| author | Zaheer Ullah Khan Anam Razzaq Ahsan Khan Naeem Ur Rehman Hira Khan Taous Khan Ashraf Ullah Khan Norah A. Althobaiti Farid Menaa Haroon Iqbal Naveed Ullah Khan |
| author_facet | Zaheer Ullah Khan Anam Razzaq Ahsan Khan Naeem Ur Rehman Hira Khan Taous Khan Ashraf Ullah Khan Norah A. Althobaiti Farid Menaa Haroon Iqbal Naveed Ullah Khan |
| author_sort | Zaheer Ullah Khan |
| collection | DOAJ |
| description | Pentazocine (PTZ), a narcotic-antagonist analgesic, has been extensively used in the treatment of initial carcinogenic or postoperative pain. Hepatic first-pass metabolism results in low oral bioavailability and high dose wastage. Herein, 10 mg (-)-Pentazocine (HPLC-grade) was incorporated to solid lipid nanoparticles (SLNs) using a double water-oil-water (<i>w</i>/<i>o</i>/<i>w</i>) emulsion by solvent emulsification–evaporation technique, followed by high shear homogenization to augment its oral bioavailability, considering the lymphatic uptake. The resulting SLNs were characterized for zeta potential (ZP), particle size (PS), and polydispersity index (PDI) using a zetasizer. The entrapment efficiency (EE) and loading capacity (LC) were calculated. Chemical interactions, through the identification of active functional groups, were assessed by Fourier-transformed infrared (FTIR) spectroscopy. The nature (crystallinity) of the SLNs was determined by X-ray diffractometry (XRD). The surface morphology was depicted by transmission electron microscopy (TEM). In vitro (in Caco-2 cells) and in vivo (in male Wistar rats) investigations were carried out to evaluate the PTZ release behavior and stability, as well as the cellular permeation, cytotoxicity, systemic pharmacokinetics, antinociceptive, anti-inflammatory, and antioxidative activities of PTZ-loaded SLNs, mainly compared to free PTZ (marketed conventional dosage form). The optimized PTZ-loaded SLN2 showed significantly higher in vitro cellular permeation and negligible cytotoxicity. The in vivo bioavailability and pharmacokinetics parameters (t<sub>1/2</sub>, Cmax) of the PTZ-loaded SLNs were also significantly improved, and the nociception and inflammation, following carrageenan-induced inflammatory pain, were markedly reduced. Concordantly, PTZ-loaded SLNs showed drastic reduction in the oxidative stress (e.g., malonaldehyde (MDA)) and proinflammatory cytokines (e.g., Interleukin (IL)-1β, -6, and TNF-α). The histological features of the paw tissue following, carrageenan-induced inflammation, were significantly improved. Taken together, the results demonstrated that PTZ-loaded SLNs can improve the bioavailability of PTZ by bypassing the hepatic metabolism via the lymphatic uptake, for controlled and sustained drug delivery. |
| first_indexed | 2024-03-09T21:14:09Z |
| format | Article |
| id | doaj.art-9814ffc858434045a6031af7416987de |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T21:14:09Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-9814ffc858434045a6031af7416987de2023-11-23T21:38:52ZengMDPI AGPharmaceutics1999-49232022-02-0114240910.3390/pharmaceutics14020409Physicochemical Characterizations and Pharmacokinetic Evaluation of Pentazocine Solid Lipid Nanoparticles against Inflammatory Pain ModelZaheer Ullah Khan0Anam Razzaq1Ahsan Khan2Naeem Ur Rehman3Hira Khan4Taous Khan5Ashraf Ullah Khan6Norah A. Althobaiti7Farid Menaa8Haroon Iqbal9Naveed Ullah Khan10Department of Pharmacy, Abbottabad Campus, COMSATS University Islamabad, Abbottabad 22060, PakistanDepartment of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, ChinaDepartment of Pharmacy, Abbottabad Campus, COMSATS University Islamabad, Abbottabad 22060, PakistanDepartment of Pharmacy, Abbottabad Campus, COMSATS University Islamabad, Abbottabad 22060, PakistanDivision of Pharmaceutics and Pharmacology, College of Pharmacy, Ohio State University, Colombus, OH 43210, USADepartment of Pharmacy, Abbottabad Campus, COMSATS University Islamabad, Abbottabad 22060, PakistanDepartment of Pharmacy, Quaid-i-Azam University, Islamabad 45320, PakistanDepartment of Biology, College of Science and Humanities-Al Quwaiiyah, Shaqra University, Al Quwaiiyah 19257, Saudi ArabiaDepartment of Oncology and Nanomedicine, California Innovations Corporation, San Diego, CA 92037, USAInstitute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences (CAS), The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou 310022, ChinaDepartment of Pharmacy, Gujrat Campus, University of Lahore, Lahore 50700, PakistanPentazocine (PTZ), a narcotic-antagonist analgesic, has been extensively used in the treatment of initial carcinogenic or postoperative pain. Hepatic first-pass metabolism results in low oral bioavailability and high dose wastage. Herein, 10 mg (-)-Pentazocine (HPLC-grade) was incorporated to solid lipid nanoparticles (SLNs) using a double water-oil-water (<i>w</i>/<i>o</i>/<i>w</i>) emulsion by solvent emulsification–evaporation technique, followed by high shear homogenization to augment its oral bioavailability, considering the lymphatic uptake. The resulting SLNs were characterized for zeta potential (ZP), particle size (PS), and polydispersity index (PDI) using a zetasizer. The entrapment efficiency (EE) and loading capacity (LC) were calculated. Chemical interactions, through the identification of active functional groups, were assessed by Fourier-transformed infrared (FTIR) spectroscopy. The nature (crystallinity) of the SLNs was determined by X-ray diffractometry (XRD). The surface morphology was depicted by transmission electron microscopy (TEM). In vitro (in Caco-2 cells) and in vivo (in male Wistar rats) investigations were carried out to evaluate the PTZ release behavior and stability, as well as the cellular permeation, cytotoxicity, systemic pharmacokinetics, antinociceptive, anti-inflammatory, and antioxidative activities of PTZ-loaded SLNs, mainly compared to free PTZ (marketed conventional dosage form). The optimized PTZ-loaded SLN2 showed significantly higher in vitro cellular permeation and negligible cytotoxicity. The in vivo bioavailability and pharmacokinetics parameters (t<sub>1/2</sub>, Cmax) of the PTZ-loaded SLNs were also significantly improved, and the nociception and inflammation, following carrageenan-induced inflammatory pain, were markedly reduced. Concordantly, PTZ-loaded SLNs showed drastic reduction in the oxidative stress (e.g., malonaldehyde (MDA)) and proinflammatory cytokines (e.g., Interleukin (IL)-1β, -6, and TNF-α). The histological features of the paw tissue following, carrageenan-induced inflammation, were significantly improved. Taken together, the results demonstrated that PTZ-loaded SLNs can improve the bioavailability of PTZ by bypassing the hepatic metabolism via the lymphatic uptake, for controlled and sustained drug delivery.https://www.mdpi.com/1999-4923/14/2/409pentazocinesolid lipid nanoparticlesoral bioavailabilityfirst-pass metabolisminflammationcontrolled and sustained drug release |
| spellingShingle | Zaheer Ullah Khan Anam Razzaq Ahsan Khan Naeem Ur Rehman Hira Khan Taous Khan Ashraf Ullah Khan Norah A. Althobaiti Farid Menaa Haroon Iqbal Naveed Ullah Khan Physicochemical Characterizations and Pharmacokinetic Evaluation of Pentazocine Solid Lipid Nanoparticles against Inflammatory Pain Model Pharmaceutics pentazocine solid lipid nanoparticles oral bioavailability first-pass metabolism inflammation controlled and sustained drug release |
| title | Physicochemical Characterizations and Pharmacokinetic Evaluation of Pentazocine Solid Lipid Nanoparticles against Inflammatory Pain Model |
| title_full | Physicochemical Characterizations and Pharmacokinetic Evaluation of Pentazocine Solid Lipid Nanoparticles against Inflammatory Pain Model |
| title_fullStr | Physicochemical Characterizations and Pharmacokinetic Evaluation of Pentazocine Solid Lipid Nanoparticles against Inflammatory Pain Model |
| title_full_unstemmed | Physicochemical Characterizations and Pharmacokinetic Evaluation of Pentazocine Solid Lipid Nanoparticles against Inflammatory Pain Model |
| title_short | Physicochemical Characterizations and Pharmacokinetic Evaluation of Pentazocine Solid Lipid Nanoparticles against Inflammatory Pain Model |
| title_sort | physicochemical characterizations and pharmacokinetic evaluation of pentazocine solid lipid nanoparticles against inflammatory pain model |
| topic | pentazocine solid lipid nanoparticles oral bioavailability first-pass metabolism inflammation controlled and sustained drug release |
| url | https://www.mdpi.com/1999-4923/14/2/409 |
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