BBD Driven Fabrication of Hydroxyapatite Engineered Risedronate Loaded Thiolated Chitosan Nanoparticles and Their In Silico, In Vitro, and Ex Vivo Studies
Risedronate sodium (RIS) exhibits limited bioavailability and undesirable gastrointestinal effects when administered orally, necessitating the development of an alternative formulation. In this study, mPEG-coated nanoparticles loaded with RIS-HA-TCS were created for osteoporosis treatment. Thiolated chitosan (TCS) was synthesized using chitosan and characterized using DSC and FTIR, with thiol immobilization assessed using Ellman's reagent. RIS-HA nanoparticles were fabricated and conjugated with synthesized TCS. Fifteen batches of RIS-HA-TCS nanoparticles were designed using the Box-Behnken design process. The nanoparticles were formulated through the ionic gelation procedure, employing tripolyphosphate (TPP) as a crosslinking agent. In silico activity comparison of RIS and RIS-HA-TCS for farnesyl pyrophosphate synthetase enzyme demonstrated a higher binding affinity for RIS. The RIS-HA-TCS nanoparticles exhibited 85.4 ± 2.21% drug entrapment efficiency, a particle size of 252.1 ± 2.44 nm, and a polydispersity index of 0.2 ± 0.01. Further conjugation with mPEG resulted in a particle size of 264.9 ± 1.91 nm, a PDI of 0.120 ± 0.01, and an encapsulation efficiency of 91.1 ± 1.17%. TEM confirmed the spherical particle size of RIS-HA-TCS and RIS-HA-TCS-mPEG. In vitro release studies demonstrated significantly higher release for RIS-HS-TCS-mPEG (95.13 ± 4.64%) compared to RIS-HA-TCS (91.74 ± 5.13%), RIS suspension (56.12 ± 5.19%), and a marketed formulation (74.69 ± 3.98%). Ex vivo gut permeation studies revealed an apparent permeability of 0.5858 × 10-1 cm/min for RIS-HA-TCS-mPEG, surpassing RIS-HA-TCS (0.4011 × 10-4 cm/min), RIS suspension (0.2005 × 10-4 cm/min), and a marketed preparation (0.3401 × 10-4 cm/min).
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
|---|---|
| Enthalten in: |
Micromachines - 14(2023), 12 vom: 30. Nov. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Saifi, Zoya [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Hydroxyapatite |
|---|
| Anmerkungen: |
Date Revised 25.12.2023 published: Electronic Citation Status PubMed-not-MEDLINE |
|---|
| doi: |
10.3390/mi14122182 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM366290150 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM366290150 | ||
| 003 | DE-627 | ||
| 005 | 20231227141121.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231227s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/mi14122182 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1238.xml |
| 035 | |a (DE-627)NLM366290150 | ||
| 035 | |a (NLM)38138351 | ||
| 035 | |a (PII)2182 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Saifi, Zoya |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a BBD Driven Fabrication of Hydroxyapatite Engineered Risedronate Loaded Thiolated Chitosan Nanoparticles and Their In Silico, In Vitro, and Ex Vivo Studies |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 25.12.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Risedronate sodium (RIS) exhibits limited bioavailability and undesirable gastrointestinal effects when administered orally, necessitating the development of an alternative formulation. In this study, mPEG-coated nanoparticles loaded with RIS-HA-TCS were created for osteoporosis treatment. Thiolated chitosan (TCS) was synthesized using chitosan and characterized using DSC and FTIR, with thiol immobilization assessed using Ellman's reagent. RIS-HA nanoparticles were fabricated and conjugated with synthesized TCS. Fifteen batches of RIS-HA-TCS nanoparticles were designed using the Box-Behnken design process. The nanoparticles were formulated through the ionic gelation procedure, employing tripolyphosphate (TPP) as a crosslinking agent. In silico activity comparison of RIS and RIS-HA-TCS for farnesyl pyrophosphate synthetase enzyme demonstrated a higher binding affinity for RIS. The RIS-HA-TCS nanoparticles exhibited 85.4 ± 2.21% drug entrapment efficiency, a particle size of 252.1 ± 2.44 nm, and a polydispersity index of 0.2 ± 0.01. Further conjugation with mPEG resulted in a particle size of 264.9 ± 1.91 nm, a PDI of 0.120 ± 0.01, and an encapsulation efficiency of 91.1 ± 1.17%. TEM confirmed the spherical particle size of RIS-HA-TCS and RIS-HA-TCS-mPEG. In vitro release studies demonstrated significantly higher release for RIS-HS-TCS-mPEG (95.13 ± 4.64%) compared to RIS-HA-TCS (91.74 ± 5.13%), RIS suspension (56.12 ± 5.19%), and a marketed formulation (74.69 ± 3.98%). Ex vivo gut permeation studies revealed an apparent permeability of 0.5858 × 10-1 cm/min for RIS-HA-TCS-mPEG, surpassing RIS-HA-TCS (0.4011 × 10-4 cm/min), RIS suspension (0.2005 × 10-4 cm/min), and a marketed preparation (0.3401 × 10-4 cm/min) | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a PEGylated nanoparticles | |
| 650 | 4 | |a hydroxyapatite | |
| 650 | 4 | |a osteoporosis | |
| 650 | 4 | |a risedronate | |
| 650 | 4 | |a thiolated chitosan | |
| 700 | 1 | |a Ralli, Tanya |e verfasserin |4 aut | |
| 700 | 1 | |a Rizwanullah, Md |e verfasserin |4 aut | |
| 700 | 1 | |a Alam, Meraj |e verfasserin |4 aut | |
| 700 | 1 | |a Vohora, Divya |e verfasserin |4 aut | |
| 700 | 1 | |a Mir, Showkat R |e verfasserin |4 aut | |
| 700 | 1 | |a Amin, Saima |e verfasserin |4 aut | |
| 700 | 1 | |a Ameen, Sadia |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Micromachines |d 2013 |g 14(2023), 12 vom: 30. Nov. |w (DE-627)NLM243194161 |x 2072-666X |7 nnns |
| 773 | 1 | 8 | |g volume:14 |g year:2023 |g number:12 |g day:30 |g month:11 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3390/mi14122182 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 14 |j 2023 |e 12 |b 30 |c 11 | ||