PMID- 34940336 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20211226 IS - 2310-2861 (Electronic) IS - 2310-2861 (Linking) VI - 7 IP - 4 DP - 2021 Dec 20 TI - Development, Optimization, and In Vitro Evaluation of Novel Oral Long-Acting Resveratrol Nanocomposite In-Situ Gelling Film in the Treatment of Colorectal Cancer. LID - 10.3390/gels7040276 [doi] LID - 276 AB - This study aimed to develop and evaluate sustained-release (SR) long-acting oral nanocomposites in-situ gelling films of resveratrol (Rv) to treat colorectal cancer. In these formulations, Rv-Soy protein (Rv-Sp) wet granules were prepared by the kneading method and then encapsulated in the sodium alginate (NA) dry films. The prepared nanocomposite in-situ gels films were characterized using dynamic light scattering, Fourier-transform infrared spectroscopy, X-ray diffraction, and scanning electron microscopy. The optimized formulations were further evaluated based on drug encapsulation efficiency, pH-drug release profile, swelling study, and storage time effects. The optimized formulation was tested for its anticancer activity against colorectal cancer cells using the cytotoxicity assessment, apoptosis testing, cell cycle analysis, gene expression analysis, and protein estimation by the reverse-transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay methods, respectively. The optimum film showed encapsulation efficiency of 97.87% +/- 0.51 and drug release of 14.45% +/- 0.043 after 8 h. All physiochemical characterizations confirmed, reasoned, and supported the drug release experiment's findings and the encapsulation assay. The Rv nanocomposite formulation showed concentration-dependent cytotoxicity enhanced apoptotic activity as compared to free Rv (p < 0.05). In addition, Rv nanocomposite formulation caused a significant increase in Bcl-2-associated protein X (Bax) and a decrease in expression of B-cell lymphoma 2, interleukin 1 beta, IL-6, and tumor necrosis factor-alpha (Bcl2, IL-1beta, IL-6, and TNF-alpha respectively) compared to that of free Rv in HCT-116 cells. These results suggest that long-acting Rv nanocomposite gels could be a promising agent for colorectal cancer treatment. FAU - Md, Shadab AU - Md S AUID- ORCID: 0000-0002-9343-1066 AD - Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia. AD - Center of Excellence for Drug Research & Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia. AD - Mohamed Saeed Tamer Chair for Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia. FAU - Abdullah, Samaa AU - Abdullah S AUID- ORCID: 0000-0001-5245-6489 AD - Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia. FAU - Alhakamy, Nabil A AU - Alhakamy NA AUID- ORCID: 0000-0002-3826-1519 AD - Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia. AD - Center of Excellence for Drug Research & Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia. AD - Mohamed Saeed Tamer Chair for Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia. FAU - Alharbi, Waleed S AU - Alharbi WS AUID- ORCID: 0000-0001-7727-6126 AD - Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia. AD - Center of Excellence for Drug Research & Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia. FAU - Ahmad, Javed AU - Ahmad J AUID- ORCID: 0000-0002-7025-751X AD - Department of Pharmaceutics, College of Pharmacy, Najran University, Najran 11001, Saudi Arabia. FAU - Shaik, Rasheed A AU - Shaik RA AUID- ORCID: 0000-0001-7959-8647 AD - Department of Pharmacology & Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia. FAU - Ansari, Mohammad Javed AU - Ansari MJ AUID- ORCID: 0000-0001-9266-7133 AD - Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia. FAU - Ibrahim, Ibrahim M AU - Ibrahim IM AUID- ORCID: 0000-0001-5280-9555 AD - Department of Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia. FAU - Ali, Javed AU - Ali J AUID- ORCID: 0000-0001-5308-0655 AD - Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India. LA - eng GR - IFPRC-151-166-2020/Deputyship for Research & Innovation, Ministry of Education in Saudi Arabia and King Abdulaziz University/ PT - Journal Article DEP - 20211220 PL - Switzerland TA - Gels JT - Gels (Basel, Switzerland) JID - 101696925 PMC - PMC8702129 OTO - NOTNLM OT - alginate film OT - colorectal cancer OT - in-situ gel OT - nanocomposites OT - oral sustained-release film OT - resveratrol OT - soy protein COIS- The authors report no declarations of interest. This work was filed in the USPTO under U.S. serial number 17/175764. EDAT- 2021/12/24 06:00 MHDA- 2021/12/24 06:01 PMCR- 2021/12/20 CRDT- 2021/12/23 12:43 PHST- 2021/12/04 00:00 [received] PHST- 2021/12/14 00:00 [revised] PHST- 2021/12/16 00:00 [accepted] PHST- 2021/12/23 12:43 [entrez] PHST- 2021/12/24 06:00 [pubmed] PHST- 2021/12/24 06:01 [medline] PHST- 2021/12/20 00:00 [pmc-release] AID - gels7040276 [pii] AID - gels-07-00276 [pii] AID - 10.3390/gels7040276 [doi] PST - epublish SO - Gels. 2021 Dec 20;7(4):276. doi: 10.3390/gels7040276.