mPEG-PCL Nanoparticles to Improve Oral Bioavailability of Acalabrutinib: Effect of Polymer Lipophilicity and Hydrophilicity on Physicochemical Properties and In Vivo Performance in Rats
<b>Background/Objectives:</b> This research focuses on the development and optimization of polymer–lipid hybrid nanoparticles (PLHNs) using two grades of mPEG-PCL co-polymers in combination with DPPC and lecithin to address the biopharmaceutical challenges of acalabrutinib (ACP), a selec...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-06-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/17/6/774 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849431421491347456 |
|---|---|
| author | Swagata Sinha Punna Rao Ravi Sahadevan Rajesh Rashmi Łukasz Szeleszczuk |
| author_facet | Swagata Sinha Punna Rao Ravi Sahadevan Rajesh Rashmi Łukasz Szeleszczuk |
| author_sort | Swagata Sinha |
| collection | DOAJ |
| description | <b>Background/Objectives:</b> This research focuses on the development and optimization of polymer–lipid hybrid nanoparticles (PLHNs) using two grades of mPEG-PCL co-polymers in combination with DPPC and lecithin to address the biopharmaceutical challenges of acalabrutinib (ACP), a selective treatment for different hematological malignancies. <b>Methods</b>: Variations in the mPEG-to-ε-caprolactone ratio influenced both the molecular weight (Mw) of the synthesized co-polymers and their aqueous phase affinity. The ACP-loaded PLHNs (ACP-PLHNs) were optimized using a circumscribed central composite design. The in vivo studies were performed in Wistar rats. <b>Results</b>: The lipophilic mPEG-PCL (Mw = 9817.67 Da) resulted in PLHNs with a particle size of 155.91 nm and 40.08% drug loading, while the hydrophilic mPEG-PCL (Mw = 23,615.84 Da) yielded PLHNs with a relatively larger size (223.46 nm) and relatively higher drug loading (46.59%). The drug release profiles were polymer-grade dependent: lipophilic ACP-PLHNs (<i>l</i>ACP-PLHNs) sustained release up to 30 h in pH 7.2 buffer, while hydrophilic ACP-PLHNs (<i>h</i>ACP-PLHNs) completed release within 24 h. Stability studies showed greater stability for <i>l</i>ACP-PLHNs, likely due to reduced molecular rearrangement from the chemically stable lipophilic co-polymer. <b>Conclusions</b>: Oral administration of both formulations exhibited a 2-fold (<i>p</i> < 0.001) improvement in the C<sub>max</sub> and AUC<sub>0-tlast</sub> and a 3.9-fold (<i>p</i> < 0.001) increase in the relatively oral bioavailability compared to the conventional ACP suspension in male wistar rats. |
| format | Article |
| id | doaj-art-21b8445ecbef4e4b85600a77a0ff6b03 |
| institution | Kabale University |
| issn | 1999-4923 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj-art-21b8445ecbef4e4b85600a77a0ff6b032025-08-20T03:27:39ZengMDPI AGPharmaceutics1999-49232025-06-0117677410.3390/pharmaceutics17060774mPEG-PCL Nanoparticles to Improve Oral Bioavailability of Acalabrutinib: Effect of Polymer Lipophilicity and Hydrophilicity on Physicochemical Properties and In Vivo Performance in RatsSwagata Sinha0Punna Rao Ravi1Sahadevan Rajesh Rashmi2Łukasz Szeleszczuk3Department of Pharmacy, Birla Institute of Technology and Science, Hyderabad Campus, Jawahar Nagar, Kapra Mandal, Medchal District, Pilani 500078, Telangana, IndiaDepartment of Pharmacy, Birla Institute of Technology and Science, Hyderabad Campus, Jawahar Nagar, Kapra Mandal, Medchal District, Pilani 500078, Telangana, IndiaDepartment of Pharmacy, Birla Institute of Technology and Science, Hyderabad Campus, Jawahar Nagar, Kapra Mandal, Medchal District, Pilani 500078, Telangana, IndiaDepartment of Organic and Physical Chemistry, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Str., 02-093 Warsaw, Poland<b>Background/Objectives:</b> This research focuses on the development and optimization of polymer–lipid hybrid nanoparticles (PLHNs) using two grades of mPEG-PCL co-polymers in combination with DPPC and lecithin to address the biopharmaceutical challenges of acalabrutinib (ACP), a selective treatment for different hematological malignancies. <b>Methods</b>: Variations in the mPEG-to-ε-caprolactone ratio influenced both the molecular weight (Mw) of the synthesized co-polymers and their aqueous phase affinity. The ACP-loaded PLHNs (ACP-PLHNs) were optimized using a circumscribed central composite design. The in vivo studies were performed in Wistar rats. <b>Results</b>: The lipophilic mPEG-PCL (Mw = 9817.67 Da) resulted in PLHNs with a particle size of 155.91 nm and 40.08% drug loading, while the hydrophilic mPEG-PCL (Mw = 23,615.84 Da) yielded PLHNs with a relatively larger size (223.46 nm) and relatively higher drug loading (46.59%). The drug release profiles were polymer-grade dependent: lipophilic ACP-PLHNs (<i>l</i>ACP-PLHNs) sustained release up to 30 h in pH 7.2 buffer, while hydrophilic ACP-PLHNs (<i>h</i>ACP-PLHNs) completed release within 24 h. Stability studies showed greater stability for <i>l</i>ACP-PLHNs, likely due to reduced molecular rearrangement from the chemically stable lipophilic co-polymer. <b>Conclusions</b>: Oral administration of both formulations exhibited a 2-fold (<i>p</i> < 0.001) improvement in the C<sub>max</sub> and AUC<sub>0-tlast</sub> and a 3.9-fold (<i>p</i> < 0.001) increase in the relatively oral bioavailability compared to the conventional ACP suspension in male wistar rats.https://www.mdpi.com/1999-4923/17/6/774co-polymerizationamphiphilic co-polymercentral composite designnanoparticlesoral pharmacokinetics |
| spellingShingle | Swagata Sinha Punna Rao Ravi Sahadevan Rajesh Rashmi Łukasz Szeleszczuk mPEG-PCL Nanoparticles to Improve Oral Bioavailability of Acalabrutinib: Effect of Polymer Lipophilicity and Hydrophilicity on Physicochemical Properties and In Vivo Performance in Rats Pharmaceutics co-polymerization amphiphilic co-polymer central composite design nanoparticles oral pharmacokinetics |
| title | mPEG-PCL Nanoparticles to Improve Oral Bioavailability of Acalabrutinib: Effect of Polymer Lipophilicity and Hydrophilicity on Physicochemical Properties and In Vivo Performance in Rats |
| title_full | mPEG-PCL Nanoparticles to Improve Oral Bioavailability of Acalabrutinib: Effect of Polymer Lipophilicity and Hydrophilicity on Physicochemical Properties and In Vivo Performance in Rats |
| title_fullStr | mPEG-PCL Nanoparticles to Improve Oral Bioavailability of Acalabrutinib: Effect of Polymer Lipophilicity and Hydrophilicity on Physicochemical Properties and In Vivo Performance in Rats |
| title_full_unstemmed | mPEG-PCL Nanoparticles to Improve Oral Bioavailability of Acalabrutinib: Effect of Polymer Lipophilicity and Hydrophilicity on Physicochemical Properties and In Vivo Performance in Rats |
| title_short | mPEG-PCL Nanoparticles to Improve Oral Bioavailability of Acalabrutinib: Effect of Polymer Lipophilicity and Hydrophilicity on Physicochemical Properties and In Vivo Performance in Rats |
| title_sort | mpeg pcl nanoparticles to improve oral bioavailability of acalabrutinib effect of polymer lipophilicity and hydrophilicity on physicochemical properties and in vivo performance in rats |
| topic | co-polymerization amphiphilic co-polymer central composite design nanoparticles oral pharmacokinetics |
| url | https://www.mdpi.com/1999-4923/17/6/774 |
| work_keys_str_mv | AT swagatasinha mpegpclnanoparticlestoimproveoralbioavailabilityofacalabrutinibeffectofpolymerlipophilicityandhydrophilicityonphysicochemicalpropertiesandinvivoperformanceinrats AT punnaraoravi mpegpclnanoparticlestoimproveoralbioavailabilityofacalabrutinibeffectofpolymerlipophilicityandhydrophilicityonphysicochemicalpropertiesandinvivoperformanceinrats AT sahadevanrajeshrashmi mpegpclnanoparticlestoimproveoralbioavailabilityofacalabrutinibeffectofpolymerlipophilicityandhydrophilicityonphysicochemicalpropertiesandinvivoperformanceinrats AT łukaszszeleszczuk mpegpclnanoparticlestoimproveoralbioavailabilityofacalabrutinibeffectofpolymerlipophilicityandhydrophilicityonphysicochemicalpropertiesandinvivoperformanceinrats |