TY - JOUR
T1 - Impact of nanocarrier aggregation on EPR-mediated tumor targeting
AU - Surya Teja, S. P.
AU - Damodharan, N.
AU - Tamilanban, T.
AU - Subramaniyan, Vetriselvan
AU - Chitra, V.
AU - Chinni, Suresh V.
AU - Wong, Ling Shing
AU - Fuloria, Neeraj Kumar
AU - Sekar, Mahendran
AU - Fuloria, Shivkanya
AU - Ramachawolran, Gobinath
AU - Selvaraj, Siddharthan
N1 - Funding Information:
The authors are thankful to the departments of NRC and Physics and Nanotechnology, SRM IST for their infrastructural support. We would also like to express our gratitude to K. Chandra Sai Kiran for his assistance during the study.
Publisher Copyright:
Copyright © 2023 Surya Teja, Damodharan, Tamilanban, Subramaniyan, Chitra, Chinni, Wong, Fuloria, Sekar, Fuloria, Ramachawolran and Selvaraj.
PY - 2023/7/21
Y1 - 2023/7/21
N2 - The aim of this study was to investigate the influence of excipients on retaining the particle size of methotrexate (MTX) loaded chitosan nanocarriers (CsNP) during lyophilization, which relates to the ability to enlarge the particle size and target specific areas. The nanocarriers were prepared using the ionic gelation technique with tripolyphosphate as a crosslinker. Three lyophilized formulations were used: nanosuspension without Lyoprotectant (NF), with mannitol (NFM), and with sucrose (NFS). The lyophilized powder intended for injection (PI) was examined to assess changes in particle size, product integrity, and comparative biodistribution studies to evaluate targeting ability. After lyophilization, NFS was excluded from in-vivo studies due to the product melt-back phenomenon. The particle size of the NF lyophile significantly increased from 176 nm to 261 nm. In contrast, NFM restricted the nanocarrier size to 194 nm and exhibited excellent cake properties. FTIR, XRD, and SEM analysis revealed the transformation of mannitol into a stable β, δ polymorphic form. Biodistribution studies showed that the nanocarriers significantly increased MTX accumulation in tumor tissue (NF = 2.04 ± 0.27; NFM = 2.73 ± 0.19) compared to the marketed PI (1.45 ± 0.25 μg), but this effect was highly dependent on the particle size. Incorporating mannitol yielded positive results in restricting particle size and favoring successful tumor targeting. This study demonstrates the potential of chitosan nanocarriers as promising candidates for targeted tumor drug delivery and cancer treatment.
AB - The aim of this study was to investigate the influence of excipients on retaining the particle size of methotrexate (MTX) loaded chitosan nanocarriers (CsNP) during lyophilization, which relates to the ability to enlarge the particle size and target specific areas. The nanocarriers were prepared using the ionic gelation technique with tripolyphosphate as a crosslinker. Three lyophilized formulations were used: nanosuspension without Lyoprotectant (NF), with mannitol (NFM), and with sucrose (NFS). The lyophilized powder intended for injection (PI) was examined to assess changes in particle size, product integrity, and comparative biodistribution studies to evaluate targeting ability. After lyophilization, NFS was excluded from in-vivo studies due to the product melt-back phenomenon. The particle size of the NF lyophile significantly increased from 176 nm to 261 nm. In contrast, NFM restricted the nanocarrier size to 194 nm and exhibited excellent cake properties. FTIR, XRD, and SEM analysis revealed the transformation of mannitol into a stable β, δ polymorphic form. Biodistribution studies showed that the nanocarriers significantly increased MTX accumulation in tumor tissue (NF = 2.04 ± 0.27; NFM = 2.73 ± 0.19) compared to the marketed PI (1.45 ± 0.25 μg), but this effect was highly dependent on the particle size. Incorporating mannitol yielded positive results in restricting particle size and favoring successful tumor targeting. This study demonstrates the potential of chitosan nanocarriers as promising candidates for targeted tumor drug delivery and cancer treatment.
KW - biodistribution
KW - cancer treatment
KW - chitosan
KW - lyophilization
KW - nanocomposite
KW - targeted tumor drug
UR - http://www.scopus.com/inward/record.url?scp=85167330263&partnerID=8YFLogxK
U2 - 10.3389/fbioe.2023.1222693
DO - 10.3389/fbioe.2023.1222693
M3 - Article
C2 - 37545888
AN - SCOPUS:85167330263
SN - 2296-4185
VL - 11
JO - Frontiers in Bioengineering and Biotechnology
JF - Frontiers in Bioengineering and Biotechnology
M1 - 1222693
ER -