PMID- 33159142
OWN - NLM
STAT- MEDLINE
DCOM- 20210310
LR  - 20210310
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 10
IP  - 1
DP  - 2020 Nov 6
TI  - Besifloxacin liposomes with positively charged additives for an improved topical 
      ocular delivery.
PG  - 19285
LID - 10.1038/s41598-020-76381-y [doi]
LID - 19285
AB  - Topical ophthalmic antibiotics show low efficacy due to the well-known 
      physiological defense mechanisms of the eye, which prevents the penetration of 
      exogenous substances. Here, we aimed to incorporate besifloxacin into liposomes 
      containing amines as positively charged additives and to evaluate the influence 
      of this charge on drug delivery in two situations: (i) iontophoretic and (ii) 
      passive treatments. Hypothesis are (i) charge might enhance the electromigration 
      component upon current application improving penetration efficiency for a burst 
      drug delivery, and (ii) positive charge might prolong formulation residence time, 
      hence drug penetration. Liposomes elaborated with phosphatidylcholine (LP PC) or 
      phosphatidylcholine and spermine (LP PC: SPM) were stable under storage at 6  masculineC 
      for 30 days, showed mucoadhesive characteristics, and were non-irritant, 
      according to HET-CAM tests. Electron paramagnetic resonance spectroscopy 
      measurements showed that neither the drug nor spermine incorporations produced 
      evident alterations in the fluidity of the liposome's membranes, which retained 
      their structural stability even under iontophoretic conditions. Mean diameter and 
      zeta potential were 177.2 +/- 2.7 nm and - 5.7 +/- 0.3 mV, respectively, for LP PC; 
      and 175.4 +/- 1.9 nm and + 19.5 +/- 1.0 mV, respectively, for LP PC:SPM. The minimal 
      inhibitory concentration (MIC) and the minimal bactericide concentration (MBC) of 
      the liposomes for P. aeruginosa showed values lower than the commercial 
      formulation (Besivance). Nevertheless, both formulations presented a similar 
      increase in permeability upon the electric current application. Hence, liposome 
      charge incorporation did not prove to be additionally advantageous for 
      iontophoretic therapy. Passive drug penetration was evaluated through a novel in 
      vitro ocular model that simulates the lacrimal flow and challenges the 
      formulation resistance in the passive delivery situation. As expected, LP PC: SPM 
      showed higher permeation than the control (Besivance). In conclusion, 
      besifloxacin incorporation into positively charged liposomes improved passive 
      topical delivery and can be a good strategy to improve topical ophthalmic 
      treatments.
FAU - Dos Santos, Giselly Almeida
AU  - Dos Santos GA
AD  - Laboratory of Food, Drugs, and Cosmetics (LTMAC), University of Brasilia, 
      Brasilia, DF, 70910-900, Brazil.
FAU - Ferreira-Nunes, Ricardo
AU  - Ferreira-Nunes R
AD  - Laboratory of Food, Drugs, and Cosmetics (LTMAC), University of Brasilia, 
      Brasilia, DF, 70910-900, Brazil.
FAU - Dalmolin, Luciana Facco
AU  - Dalmolin LF
AD  - School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, 
      Ribeirao Preto, SP, 14040-903, Brazil.
FAU - Dos Santos Re, Ana Carolina
AU  - Dos Santos Re AC
AD  - School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, 
      Ribeirao Preto, SP, 14040-903, Brazil.
FAU - Anjos, Jorge Luiz Vieira
AU  - Anjos JLV
AD  - Institute of Physics, Federal University of Goias, Catalao, GO, 75704-020, 
      Brazil.
FAU - Mendanha, Sebastiao Antonio
AU  - Mendanha SA
AD  - Institute of Physics, Federal University of Goias, Goiania, GO, 74690-900, 
      Brazil.
FAU - Aires, Carolina Patricia
AU  - Aires CP
AD  - School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, 
      Ribeirao Preto, SP, 14040-903, Brazil.
FAU - Lopez, Renata F V
AU  - Lopez RFV
AD  - School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, 
      Ribeirao Preto, SP, 14040-903, Brazil.
FAU - Cunha-Filho, Marcilio
AU  - Cunha-Filho M
AD  - Laboratory of Food, Drugs, and Cosmetics (LTMAC), University of Brasilia, 
      Brasilia, DF, 70910-900, Brazil.
FAU - Gelfuso, Guilherme M
AU  - Gelfuso GM
AD  - Laboratory of Food, Drugs, and Cosmetics (LTMAC), University of Brasilia, 
      Brasilia, DF, 70910-900, Brazil.
FAU - Gratieri, Tais
AU  - Gratieri T
AD  - Laboratory of Food, Drugs, and Cosmetics (LTMAC), University of Brasilia, 
      Brasilia, DF, 70910-900, Brazil. tgratieri@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201106
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Azepines)
RN  - 0 (Fluoroquinolones)
RN  - 0 (Liposomes)
RN  - 0 (Phosphatidylcholines)
RN  - BFE2NBZ7NX (besifloxacin)
SB  - IM
MH  - Administration, Ophthalmic
MH  - Animals
MH  - *Azepines/chemistry/pharmacokinetics/pharmacology
MH  - Eye/*metabolism
MH  - *Fluoroquinolones/chemistry/pharmacokinetics/pharmacology
MH  - Liposomes
MH  - Permeability
MH  - Phosphatidylcholines/chemistry/pharmacokinetics/pharmacology
MH  - Swine
PMC - PMC7648625
COIS- The authors declare no competing interests.
EDAT- 2020/11/08 06:00
MHDA- 2021/03/11 06:00
PMCR- 2020/11/06
CRDT- 2020/11/07 05:32
PHST- 2020/05/28 00:00 [received]
PHST- 2020/10/22 00:00 [accepted]
PHST- 2020/11/07 05:32 [entrez]
PHST- 2020/11/08 06:00 [pubmed]
PHST- 2021/03/11 06:00 [medline]
PHST- 2020/11/06 00:00 [pmc-release]
AID - 10.1038/s41598-020-76381-y [pii]
AID - 76381 [pii]
AID - 10.1038/s41598-020-76381-y [doi]
PST - epublish
SO  - Sci Rep. 2020 Nov 6;10(1):19285. doi: 10.1038/s41598-020-76381-y.