PMID- 35456705
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 1999-4923 (Print)
IS  - 1999-4923 (Electronic)
IS  - 1999-4923 (Linking)
VI  - 14
IP  - 4
DP  - 2022 Apr 15
TI  - Effect of Solvents, Stabilizers and the Concentration of Stabilizers on the 
      Physical Properties of Poly(d,l-lactide-co-glycolide) Nanoparticles: 
      Encapsulation, In Vitro Release of Indomethacin and Cytotoxicity against 
      HepG2-Cell.
LID - 10.3390/pharmaceutics14040870 [doi]
LID - 870
AB  - A biocompatible, biodegradable and FDA-approved polymer [Poly lactic-co-glycolic 
      acid (PLGA)] was used to prepare the nanoparticles (NPs) to observe the effect of 
      solvents, stabilizers and their concentrations on the physical properties of the 
      PLGA-NPs, following the encapsulation and in vitro release of Indomethacin (IND). 
      PLGA-NPs were prepared by the single-emulsion solvent evaporation technique using 
      dichloromethane (DCM)/chloroform as the organic phase with Polyvinyl-alcohol 
      (PVA)/Polyvinylpyrrolidone (PVP) as stabilizers to encapsulate IND. The effects 
      of different proportions of PVA/PVP with DCM/chloroform on the physiochemical 
      properties (particle size, the polydispersity index, the zeta potential by 
      Malvern Zetasizer and morphology by SEM) of the NPs were investigated. DSC was 
      used to check the physical state, the possible complexation of PLGA with 
      stabilizer(s) and the crystallinity of the encapsulated drug. Stabilizers at all 
      concentrations produced spherical, regular-shaped, smooth-surfaced discrete NPs. 
      Average size of 273.2-563.9 nm was obtained when PVA (stabilizer) with DCM, 
      whereas it ranged from 317.6 to 588.1 nm with chloroform. The particle size was 
      273.2-563.9 nm when PVP was the stabilizer with DCM, while it was 381.4-466.6 nm 
      with chloroform. The zeta potentials of PVA-stabilized NPs were low and negative 
      (-0.62 mV) while they were comparatively higher and positive for PVP-stabilized 
      NPs (+17.73 mV). Finally, drug-loaded optimal NPs were composed of PLGA (40 mg) 
      and IND (4 mg) in 1 mL DCM/chloroform with PVA/PVP (1-3%), which resulted in 
      sufficient encapsulation (54.94-74.86%) and drug loading (4.99-6.81%). No 
      endothermic peak of PVA/PVP appeared in the optimized formulation, which 
      indicated the amorphous state of IND in the core of the PLGA-NPs. The in vitro 
      release study indicated a sustained release of IND (32.83-52.16%) from the 
      PLGA-NPs till 72 h and primarily followed the Higuchi matrix release kinetics 
      followed by Korsmeyer-Peppas models. The cell proliferation assay clearly 
      established that the organic solvents used to prepare PLGA-NPs had evaporated. 
      The PLGA-NPs did not show any particular toxicity in the HepG2 cells within the 
      dose range of IND (250-500 microg/mL) and at an equivalent concentration of PLGA-NPs 
      (3571.4-7142.7 microg/mL). The cytotoxicity of the hepatotoxic drug (IND) was reduced 
      by its encapsulation into PLGA-NPs. The outcomes of this investigation could be 
      implemented to prepare PLGA-NPs of acceptable properties for the encapsulation of 
      low/high molecular weight drugs. It would be useful for further in vitro and in 
      vivo applications to use this delivery system.
FAU - Alkholief, Musaed
AU  - Alkholief M
AD  - Nanobiotechnology Unit, Department of Pharmaceutics, College of Pharmacy, King 
      Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
FAU - Kalam, Mohd Abul
AU  - Kalam MA
AUID- ORCID: 0000-0002-5713-8858
AD  - Nanobiotechnology Unit, Department of Pharmaceutics, College of Pharmacy, King 
      Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
FAU - Anwer, Md Khalid
AU  - Anwer MK
AUID- ORCID: 0000-0002-5227-3954
AD  - Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz 
      University, Al-Kharj 11942, Saudi Arabia.
FAU - Alshamsan, Aws
AU  - Alshamsan A
AUID- ORCID: 0000-0002-8950-6571
AD  - Nanobiotechnology Unit, Department of Pharmaceutics, College of Pharmacy, King 
      Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
LA  - eng
PT  - Journal Article
DEP - 20220415
PL  - Switzerland
TA  - Pharmaceutics
JT  - Pharmaceutics
JID - 101534003
PMC - PMC9028368
OTO - NOTNLM
OT  - Indomethacin
OT  - PLGA
OT  - cytotoxicity
OT  - drug release
OT  - encapsulation
OT  - morphology
OT  - nanoparticles
OT  - particle-size
OT  - solvents
OT  - stabilizers
COIS- The authors declare no any conflict of interest.
EDAT- 2022/04/24 06:00
MHDA- 2022/04/24 06:01
PMCR- 2022/04/15
CRDT- 2022/04/23 01:10
PHST- 2022/02/06 00:00 [received]
PHST- 2022/03/20 00:00 [revised]
PHST- 2022/04/12 00:00 [accepted]
PHST- 2022/04/23 01:10 [entrez]
PHST- 2022/04/24 06:00 [pubmed]
PHST- 2022/04/24 06:01 [medline]
PHST- 2022/04/15 00:00 [pmc-release]
AID - pharmaceutics14040870 [pii]
AID - pharmaceutics-14-00870 [pii]
AID - 10.3390/pharmaceutics14040870 [doi]
PST - epublish
SO  - Pharmaceutics. 2022 Apr 15;14(4):870. doi: 10.3390/pharmaceutics14040870.