PMID- 35017012
OWN - NLM
STAT- MEDLINE
DCOM- 20220223
LR  - 20220223
IS  - 1879-0720 (Electronic)
IS  - 0928-0987 (Linking)
VI  - 171
DP  - 2022 Apr 1
TI  - A new nanosuspension prepared with wet milling method for oral delivery of highly 
      variable drug Cyclosporine A: development, optimization and in vivo evaluation.
PG  - 106123
LID - S0928-0987(22)00008-2 [pii]
LID - 10.1016/j.ejps.2022.106123 [doi]
AB  - Cyclosporine A (CsA) is a cyclic polypeptide, that has been widely used for 
      immunosuppression. This study aims to develop nanosuspension for oral 
      administration of CsA using the wet milling (WM) method one of the top-down 
      technologies. The WM method was optimized by studying the effects of critical 
      process parameters for WM on the particle size (PS), particle size distribution 
      (PDI), and zeta potential (ZP) of nanosuspensions using the Design of Experiment 
      (DoE) approach. Nanosuspension was developed using hydroxypropyl methylcellulose 
      (HPMC) and sodium dodecyl sulfate (SDS) and in vitro characterization studies 
      were performed. In vitro dissolution and in vivo pharmacokinetic studies were 
      conducted with biorelevant media (fasted and fed state simulated fluids) and 
      fasted and fed states in rats, respectively. In vivo immunological studies were 
      also performed. PS, PDI, and ZP values for nanosuspension were approximately 
      600 nm, 0.4, -25 mV, respectively. The solubility of CsA was increased by 
      4.5-folds by nanosuspensions. Dissolution studies showed that nanosuspension had 
      higher dissolution than the commercial product in the FeSSIF medium. The 
      pharmacokinetic study indicated that AUC(0-24) values of CsA nanosuspension were 
      to be 2.09 and 5.51-fold higher than coarse powder in fasted and fed conditions, 
      respectively. Immunological studies were carried out after oral administration of 
      nanosuspension for 21 days, the ratio of CD4+/CD8+ was found to be more 
      acceptable than the commercial product. These results demonstrated that 
      nanosuspension is a promising approach for increasing the bioavailability and 
      avoiding the food effect on absorption of CsA which one of the highly variable 
      drugs.
CI  - Copyright (c) 2022. Published by Elsevier B.V.
FAU - Pinar, Sila Gulbag
AU  - Pinar SG
AD  - Gazi University, Faculty of Pharmacy, Department of Pharmaceutical Technology, 
      Etiler, 06330, Yenimahalle, Ankara, Turkey; Suleyman Demirel University, Faculty 
      of Pharmacy, Department of Pharmaceutical Technology, 32260, Cunur, Isparta, 
      Turkey.
FAU - Canpinar, Hande
AU  - Canpinar H
AD  - Hacettepe University, Cancer Institute, Department of Basic Oncology, 06100, 
      Sihhiye, Ankara, Turkey.
FAU - Tan, Cagman
AU  - Tan C
AD  - Hacettepe University, Faculty of Medicine, Institute of Child Health, 06100, 
      Sihhiye, Ankara, Turkey.
FAU - Celebi, Nevin
AU  - Celebi N
AD  - Gazi University, Faculty of Pharmacy, Department of Pharmaceutical Technology, 
      Etiler, 06330, Yenimahalle, Ankara, Turkey; Baskent University, Faculty of 
      Pharmacy, Department of Pharmaceutical Technology, 06790, Etimesgut, Ankara, 
      Turkey. Electronic address: fncelebi@baskent.edu.tr.
LA  - eng
PT  - Journal Article
DEP - 20220110
PL  - Netherlands
TA  - Eur J Pharm Sci
JT  - European journal of pharmaceutical sciences : official journal of the European 
      Federation for Pharmaceutical Sciences
JID - 9317982
RN  - 0 (Suspensions)
RN  - 83HN0GTJ6D (Cyclosporine)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - Biological Availability
MH  - *Cyclosporine
MH  - *Nanoparticles/chemistry
MH  - Particle Size
MH  - Rats
MH  - Solubility
MH  - Suspensions
OTO - NOTNLM
OT  - Cyclosporine a
OT  - Dissolution
OT  - Nanosuspension
OT  - Pharmacokinetic
OT  - T lymphocyte subsets
OT  - Top-down technology
EDAT- 2022/01/13 06:00
MHDA- 2022/02/24 06:00
CRDT- 2022/01/12 05:52
PHST- 2021/07/06 00:00 [received]
PHST- 2021/12/30 00:00 [revised]
PHST- 2022/01/03 00:00 [accepted]
PHST- 2022/01/13 06:00 [pubmed]
PHST- 2022/02/24 06:00 [medline]
PHST- 2022/01/12 05:52 [entrez]
AID - S0928-0987(22)00008-2 [pii]
AID - 10.1016/j.ejps.2022.106123 [doi]
PST - ppublish
SO  - Eur J Pharm Sci. 2022 Apr 1;171:106123. doi: 10.1016/j.ejps.2022.106123. Epub 
      2022 Jan 10.