PMID- 28487189
OWN - NLM
STAT- MEDLINE
DCOM- 20180108
LR  - 20181202
IS  - 1873-3476 (Electronic)
IS  - 0378-5173 (Linking)
VI  - 526
IP  - 1-2
DP  - 2017 Jun 30
TI  - Mucopenetrating nanoparticles for enhancement of oral bioavailability of 
      furosemide: In vitro and in vivo evaluation/sub-acute toxicity study.
PG  - 366-379
LID - S0378-5173(17)30383-6 [pii]
LID - 10.1016/j.ijpharm.2017.04.072 [doi]
AB  - The aim of this study was to formulate and evaluate chitosan (CS)/alginate (ALG) 
      nanoparticles (NPs) loaded with furosemide (FSM) in an attempt to enhance its 
      release, permeability and bioavailability. Non-everted gut sac method was used to 
      evaluate the ex vivo permeation of FSM from its suspension and the selected 
      CS/ALG NPs formulation. The pharmacokinetic parameters of FSM subsequent to oral 
      administration of the selected formulation were assessed in rats. In vivo 
      subacute toxicity study of the prepared blank and FSM loaded formulations was 
      evaluated in rats. The selected optimized formulation (F3) showed optimum 
      particle size (PS), polydispersity index (PDI), zeta potential (ZP) and 
      acceptable percentage entrapment efficiency (%EE) of 253.8nm+/-4.6, 0.25+/-0.03, 
      -35mV+/-1 and 96%+/-1, respectively. The release profile of FSM from the selected 
      formulation was characterized by initial burst effect in 0.1N HCl. Scanning 
      electron microscope (SEM) demonstrated a smooth surface and spherical shape for 
      the lyophilized optimized NPs. Selected CS/ALG NPs (F3) presented a significant 
      enhancement (p</=0.01) in permeation parameters of FSM as well as in T(max), 
      C(max), AUC(0-24) and AUC(0-infinity). Subacute toxicity study results revealed that the 
      selected formulation was safe and nontoxic. The histopathological inspection of 
      the stomach and small intestine tissues of the loaded NPs (F3) and blank groups 
      reflected no obvious signs of cellular toxicity or inflammatory reaction. CS/ALG 
      NPs loaded with FSM enhanced both drug release and mucus-penetrating ability 
      leading to an overall increase in FSM bioavailability. In addition, the in vivo 
      subacute toxicity study results indicated the safety of the prepared NPs for oral 
      drug delivery.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Radwan, Salma El-Sayed
AU  - Radwan SE
AD  - Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, 
      Alexandria, Egypt.
FAU - Sokar, Magda Samir
AU  - Sokar MS
AD  - Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, 
      Alexandria, Egypt.
FAU - Abdelmonsif, Doaa Ali
AU  - Abdelmonsif DA
AD  - Department of Medical Biochemistry, Faculty of Medicine, Alexandria University, 
      Egypt.
FAU - El-Kamel, Amal Hassan
AU  - El-Kamel AH
AD  - Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, 
      Alexandria, Egypt. Electronic address: amalelkamel@yahoo.com.
LA  - eng
PT  - Journal Article
DEP - 20170506
PL  - Netherlands
TA  - Int J Pharm
JT  - International journal of pharmaceutics
JID - 7804127
RN  - 0 (Drug Carriers)
RN  - 7LXU5N7ZO5 (Furosemide)
RN  - 9012-76-4 (Chitosan)
SB  - IM
MH  - Animals
MH  - Biological Availability
MH  - Chitosan/*chemistry
MH  - Drug Carriers/*chemistry
MH  - Furosemide/*pharmacokinetics
MH  - Nanoparticles/*chemistry
MH  - Rats
OTO - NOTNLM
OT  - Furosemide
OT  - Mucopenetration
OT  - Nanoparticles
OT  - Pharmacokinetics
OT  - in vivo sub-acute toxicity
EDAT- 2017/05/11 06:00
MHDA- 2018/01/09 06:00
CRDT- 2017/05/11 06:00
PHST- 2017/03/02 00:00 [received]
PHST- 2017/04/25 00:00 [revised]
PHST- 2017/04/28 00:00 [accepted]
PHST- 2017/05/11 06:00 [pubmed]
PHST- 2018/01/09 06:00 [medline]
PHST- 2017/05/11 06:00 [entrez]
AID - S0378-5173(17)30383-6 [pii]
AID - 10.1016/j.ijpharm.2017.04.072 [doi]
PST - ppublish
SO  - Int J Pharm. 2017 Jun 30;526(1-2):366-379. doi: 10.1016/j.ijpharm.2017.04.072. 
      Epub 2017 May 6.