PMID- 34121838
OWN - NLM
STAT- MEDLINE
DCOM- 20211207
LR  - 20220423
IS  - 1177-8881 (Electronic)
IS  - 1177-8881 (Linking)
VI  - 15
DP  - 2021
TI  - Topical Delivery of Levocarnitine to the Cornea and Anterior Eye by 
      Thermosensitive in-situ Gel for Dry Eye Disease.
PG  - 2357-2373
LID - 10.2147/DDDT.S309648 [doi]
AB  - PURPOSE: To prepare the levocarnitine thermosensitive in situ gel (LCTG) and 
      evaluate its effect on dry eye disease (DED). METHODS: Draize eye irritation test 
      and other examinations were used to evaluate the eye irritation after multiple 
      administration of LCTG. The Schirmer test, fluorescein sodium staining, HE 
      staining and TUNEL staining were used to detect the tear secretion, corneal 
      injury, histopathological changes of the cornea and lacrimal gland, and the 
      apoptosis rate of cornea epithelial cells after 3 days of the administration. The 
      conjunctival goblet cell density was detected by PAS staining, and the expression 
      levels of matrix metalloproteinase-3 (MMP-3) and matrix metalloproteinase-9 
      (MMP-9) of corneal epithelial cells were detected by immunofluorescence staining 
      after 7 days of the administration. RESULTS: LCTG is non-irritating to rabbit 
      eyes and has good biocompatibility. LCTG administration for 3 days can 
      significantly increase the amount of tear secretion in mice with DED, promote 
      corneal epithelial integrity and central corneal epithelium thickness recovery, 
      and improve the pathological morphology and structure of corneal and lacrimal 
      gland tissues, and reduce the apoptosis rate of the corneal epithelial cells. 
      After 7 days of the administration, the preparation can promote the proliferation 
      of conjunctival goblet cells and down-regulate the cornea expression levels of 
      MMP-3 and MMP-9 in epithelial cells. CONCLUSION: The LCTG has a good curative 
      effect on mice with DED, and the overall curative effect is better than that of 
      levocarnitine solution.
CI  - (c) 2021 Ma et al.
FAU - Ma, Baorui
AU  - Ma B
AD  - School of Chinese Materia Medica, Beijing University of Chinese Medicine, 
      Beijing, People's Republic of China.
FAU - Pang, Linnuo
AU  - Pang L
AD  - School of Chinese Materia Medica, Beijing University of Chinese Medicine, 
      Beijing, People's Republic of China.
FAU - Huang, Pingqing
AU  - Huang P
AD  - School of Chinese Materia Medica, Beijing University of Chinese Medicine, 
      Beijing, People's Republic of China.
FAU - Bai, Jie
AU  - Bai J
AD  - School of Chinese Materia Medica, Beijing University of Chinese Medicine, 
      Beijing, People's Republic of China.
FAU - Zhang, Zhiqin
AU  - Zhang Z
AD  - School of Chinese Materia Medica, Beijing University of Chinese Medicine, 
      Beijing, People's Republic of China.
FAU - Wu, Huimin
AU  - Wu H
AD  - School of Chinese Materia Medica, Beijing University of Chinese Medicine, 
      Beijing, People's Republic of China.
FAU - Cai, Mengru
AU  - Cai M
AD  - School of Chinese Materia Medica, Beijing University of Chinese Medicine, 
      Beijing, People's Republic of China.
FAU - Yang, Jin
AU  - Yang J
AD  - School of Chinese Materia Medica, Beijing University of Chinese Medicine, 
      Beijing, People's Republic of China.
FAU - Xu, Yuchen
AU  - Xu Y
AD  - School of Chinese Materia Medica, Beijing University of Chinese Medicine, 
      Beijing, People's Republic of China.
FAU - Yin, Xingbin
AU  - Yin X
AUID- ORCID: 0000-0003-3077-1626
AD  - School of Chinese Materia Medica, Beijing University of Chinese Medicine, 
      Beijing, People's Republic of China.
FAU - Qu, Changhai
AU  - Qu C
AD  - School of Chinese Materia Medica, Beijing University of Chinese Medicine, 
      Beijing, People's Republic of China.
FAU - Ni, Jian
AU  - Ni J
AD  - School of Chinese Materia Medica, Beijing University of Chinese Medicine, 
      Beijing, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20210602
PL  - New Zealand
TA  - Drug Des Devel Ther
JT  - Drug design, development and therapy
JID - 101475745
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.4.24.17 (Mmp3 protein, mouse)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - EC 3.4.24.35 (Mmp9 protein, mouse)
RN  - S7UI8SM58A (Carnitine)
SB  - IM
MH  - Administration, Ophthalmic
MH  - Animals
MH  - Carnitine/*administration & dosage/pharmacology/toxicity
MH  - Cornea/*metabolism
MH  - Disease Models, Animal
MH  - *Drug Delivery Systems
MH  - Dry Eye Syndromes/*drug therapy
MH  - Epithelium, Corneal/drug effects/metabolism
MH  - Female
MH  - Gene Expression Regulation/drug effects
MH  - Goblet Cells/drug effects/metabolism
MH  - Matrix Metalloproteinase 3/genetics
MH  - Matrix Metalloproteinase 9/genetics
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Rabbits
MH  - Temperature
MH  - Treatment Outcome
PMC - PMC8188229
OTO - NOTNLM
OT  - cornea
OT  - delivery
OT  - dry eye disease
OT  - in situ gel
OT  - levocarnitine
COIS- The authors declare no potential conflicts of interest for this work.
EDAT- 2021/06/15 06:00
MHDA- 2021/12/15 06:00
PMCR- 2021/06/02
CRDT- 2021/06/14 09:32
PHST- 2021/03/05 00:00 [received]
PHST- 2021/05/13 00:00 [accepted]
PHST- 2021/06/14 09:32 [entrez]
PHST- 2021/06/15 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/06/02 00:00 [pmc-release]
AID - 309648 [pii]
AID - 10.2147/DDDT.S309648 [doi]
PST - epublish
SO  - Drug Des Devel Ther. 2021 Jun 2;15:2357-2373. doi: 10.2147/DDDT.S309648. 
      eCollection 2021.