PMID- 37754394
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231003
IS  - 2310-2861 (Electronic)
IS  - 2310-2861 (Linking)
VI  - 9
IP  - 9
DP  - 2023 Sep 3
TI  - Imiquimod-Loaded Chitosan-Decorated Di-Block and Tri-Block Polymeric 
      Nanoparticles Loaded In Situ Gel for the Management of Cervical Cancer.
LID - 10.3390/gels9090713 [doi]
LID - 713
AB  - BACKGROUND: Cervical intraepithelial neoplasia, the predisposing factor for 
      cervical cancer (CC), is caused by human papillomavirus (HPV) infection and can 
      be treated with imiquimod (IMQ). However, poor water solubility and side effects 
      such as local inflammation can render IMQ ineffective. The aim of this study is 
      to design a prolonged release nano system in combination with 
      mucoadhesive-thermosensitive properties for an effective vaginal drug delivery. 
      METHODS: Polylactic-co-glycolic acid (PLGA), polycaprolactone (PCL), poly 
      lactide-co-caprolactone (PLA-PCL), and poly 
      L-lactide-co-caprolactone-co-glycolide (PLGA-PCL) were used to create IMQ 
      nanoparticles. Chitosan (CS) was then added to the surfaces of the IMQ NPs for 
      its mucoadhesive properties. The NPs were then incorporated into poloxamer 
      hydrogels. The NPs' size and morphology, encapsulation efficiency (EE), in vitro 
      drug release, gel characterization, ex vivo drug permeation, and in vitro safety 
      and efficacy were characterized. RESULTS: Two batches of NPs were prepared, IMQ 
      NPs and CS-coated NPs (CS-IMQ NPs). In general, both types of NPs were uniformly 
      spherical in shape with average particle sizes of 237.3 +/- 4.7 and 278.2 +/- 5.4 nm 
      and EE% of 61.48 +/- 5.19% and 37.73 +/- 2.88 for IMQ NPs and CS-IMQ NPs, 
      respectively. Both systems showed prolonged drug release of about 80 and 70% for 
      IMQ NPs and CS-IMQ NPs, respectively, within 48 h. The gelation temperatures for 
      the IMQ NPs and CS-IMQ NPs were 30 and 32  degrees C, respectively; thus, suitable for 
      vaginal application. Although ex vivo permeability showed that CS-IMQ NPs showed 
      superior penetration compared to IMQ NPs, both systems enhanced drug penetration 
      (283 and 462 microg/cm(2) for IMQ NPs and CS-IMQ NPs, respectively) relative to the 
      control (60 microg/cm(2)). Both systems reduced the viability of cervical cancer 
      cells, with a minimal effect of the normal vaginal epithelium. However, IMQ NPs 
      exhibited a more pronounced cytotoxic effect. Both systems were able to reduce 
      the production of inflammatory cytokines by at least 25% in comparison to free 
      IMQ. CONCLUSION: IMQ and CS-IMQ NP in situ gels enhanced stability and drug 
      release, and improved IMQ penetration through the vaginal tissues. Additionally, 
      the new systems were able to increase the cytotoxic effect of IMQ against CC 
      cells with a reduction in inflammatory responses. Thus, we believe that these 
      systems could be a good alternative to commercial IMQ systems for the management 
      of CC.
FAU - Almomen, Aliyah
AU  - Almomen A
AD  - Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud 
      University, Riyadh 11495, Saudi Arabia.
FAU - Badran, Mohamed
AU  - Badran M
AUID- ORCID: 0000-0003-1814-0215
AD  - Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 
      11495, Saudi Arabia.
FAU - Alhowyan, Adel Ali
AU  - Alhowyan AA
AUID- ORCID: 0000-0002-6244-9407
AD  - Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 
      11495, Saudi Arabia.
FAU - Alkholief, Musaed
AU  - Alkholief M
AD  - Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 
      11495, Saudi Arabia.
FAU - Alshamsan, Aws
AU  - Alshamsan A
AUID- ORCID: 0000-0002-8950-6571
AD  - Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 
      11495, Saudi Arabia.
LA  - eng
GR  - IFKSUDR_H221/The authors extend their appreciation to the Deputyship for Research 
      & Innovation, Ministry of Education in Saudi Arabia for funding this research 
      work through the project number IFKSUDR_H221./
PT  - Journal Article
DEP - 20230903
PL  - Switzerland
TA  - Gels
JT  - Gels (Basel, Switzerland)
JID - 101696925
PMC - PMC10530705
OTO - NOTNLM
OT  - cervical cancer
OT  - chitosan
OT  - imiquimod
OT  - in situ gels
OT  - nanoparticles
OT  - vaginal drug delivery
COIS- The authors declare no conflict of interest.
EDAT- 2023/09/27 12:41
MHDA- 2023/09/27 12:42
PMCR- 2023/09/03
CRDT- 2023/09/27 08:55
PHST- 2023/07/25 00:00 [received]
PHST- 2023/08/20 00:00 [revised]
PHST- 2023/08/28 00:00 [accepted]
PHST- 2023/09/27 12:42 [medline]
PHST- 2023/09/27 12:41 [pubmed]
PHST- 2023/09/27 08:55 [entrez]
PHST- 2023/09/03 00:00 [pmc-release]
AID - gels9090713 [pii]
AID - gels-09-00713 [pii]
AID - 10.3390/gels9090713 [doi]
PST - epublish
SO  - Gels. 2023 Sep 3;9(9):713. doi: 10.3390/gels9090713.