Formulation of surface-functionalized hyaluronic acid-coated thiolated chitosan nano-formulation for the delivery of vincristine in prostate cancer: A multifunctional targeted drug delivery approach

Naseer, Faiza; Ahmad, Tahir; Kousar, Kousain; Kakar, Salik Javed; Gul, Rabia; Anjum, Sadia

doi:10.1016/j.jddst.2022.103545

Cited by 20 publications

(60 citation statements)

References 37 publications

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“…Small-sized nanoparticles have a high surface-to-volume ratio and rapidly release the encapsulated material as they adhere to the surface of the cell membrane. 24 OMV-loaded TCs-NF zeta potential decreased from ±17.8 mV to ±11.5 mV after coating with HA, similar surface charge measurements related outcomes were shown by Prego with co-workers in 2010. 33 They also stated that the surface charge in recombinant hepatitis B surface antigen-loaded in chitosan nanoparticles was decreased as compared to the blank nanoparticles from 30 mV to 5.9 mV.…”

supporting

confidence: 84%

“…The increase in cellular uptake is due to the formation of both disulfide and covalent bonds between cysteine-rich mucosa and polymer, which is a more favorable binding interaction compared to electrostatic interactions of pure chitosan. 24 Computational studies strongly stated the binding of HA with the CD44-R at both A & B binding sites from NFs of HA-coated TCs in prostate cancer cells. Furthermore, the host and viral protein-protein docking studies were performed and revealed significant interaction of viral hemagglutinin capsid protein with human caspase-I, NLRP3, and TNF-and interaction of the viral fusion protein with COX-II and caspase.…”

Section: Discussionmentioning

confidence: 96%

“…The 0.5 mg/mL HA was used for the outermost coating around the formulation, it was then centrifuged, lyophilized, and further stored at 4°C. 24 Preparation of OMV-Loaded NF…”

Section: Oncolytic Measles Virus (Omv) Strainmentioning

confidence: 99%

“…All assays were performed according to the protocols mentioned in a previous study. 24 Viral Quantification from Prepared NFs…”

Section: Characterization Of Omv-loaded Nfs Physiochemical and Morpho...mentioning

confidence: 99%

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Formulation for the Targeted Delivery of a Vaccine Strain of Oncolytic Measles Virus (OMV) in Hyaluronic Acid Coated Thiolated Chitosan as a Green Nanoformulation for the Treatment of Prostate Cancer: A Viro-Immunotherapeutic Approach

Naseer¹,

Ahmad²,

Kousar³

et al. 2023

IJN

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Background: Oncolytic viruses are reported as dynamite against cancer treatment nowadays. Methodology: In the present work, a live attenuated oral measles vaccine (OMV) strain was used to formulate a polymeric surfacefunctionalized ligand-based nanoformulation (NF). OMV (half dose: not less than 500 TCID units; 0.25 mL) was encapsulated in thiolated chitosan and outermost coating with hyaluronic acid by ionic gelation method characterizing parameters was performed. Results and Discussion: CD44 high expression was confirmed in prostatic adenocarcinoma (PRAD) by GEPIA which extracted data of normal and cancer tissue from GTEx and TCGA. Bioinformatics tools confirmed the viral hemagglutinin capsid protein interaction with human Caspase-I, NLRP3, and TNF-α and viral fusion protein interaction with COX-II and Caspase-I after successful delivery of MV encapsulated in NFs due to high affinity of hyaluronic acid with CD44 on the surface of prostate cancer cells. Particle size = 275.6 mm, PDI = 0.372, and ±11.5 zeta potential were shown by zeta analysis, while the thiolated group in NFs was confirmed by FTIR and Raman analysis. SEM and XRD showed a spherical smooth surface and crystalline nature, respectively, while TEM confirmed virus encapsulation within nanoparticles, which makes it very useful in targeted virus delivery systems. The virus was released from NFs in a sustained but continuous release pattern till 48 h. The encapsulated virus titer was calculated as 2.34×107 TCID50/mL units, which showed syncytia formation on post-day infection 7. Multiplicities of infection 0.1, 0.5, 1, 3, 5, 10, 15, and 20 of HA-coated OMV-loaded NFs as compared to MV vaccine on PC3 was inoculated with IC50 of 5.1 and 3.52, respectively, and growth inhibition was seen after 72 h via MTT assay which showed apoptotic cancer cell death. Conclusion: Active targeted, efficacious, and sustained delivery of formulated oncolytic MV is a potent moiety in cancer treatment at lower doses with safe potential for normal prostate cells.

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supporting

confidence: 84%

Section: Discussionmentioning

confidence: 96%

“…The 0.5 mg/mL HA was used for the outermost coating around the formulation, it was then centrifuged, lyophilized, and further stored at 4°C. 24 Preparation of OMV-Loaded NF…”

Section: Oncolytic Measles Virus (Omv) Strainmentioning

confidence: 99%

“…All assays were performed according to the protocols mentioned in a previous study. 24 Viral Quantification from Prepared NFs…”

Section: Characterization Of Omv-loaded Nfs Physiochemical and Morpho...mentioning

confidence: 99%

See 2 more Smart Citations

Formulation for the Targeted Delivery of a Vaccine Strain of Oncolytic Measles Virus (OMV) in Hyaluronic Acid Coated Thiolated Chitosan as a Green Nanoformulation for the Treatment of Prostate Cancer: A Viro-Immunotherapeutic Approach

Naseer¹,

Ahmad²,

Kousar³

et al. 2023

IJN

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“…It has promising therapeutic applications because it can undergo many conformational changes, can conjugate with compatible ligands, crosslink bioactive compounds due to the presence of N- acetyl groups, and has primary and secondary hydroxyl groups, glucuronic acid, and carboxylic acid groups at functionally reactive sites. Surface functionalization of nano DDS with hyaluronic acid (HA) has benefits of increased blood circulation time, enhanced biocompatibility, and active targeting of CD44 receptors on cancer cells ( Naseer et al, 2011 ). CD44, also known as H-CAM is a stem-like a receptor that has been found to be over-expressed on solid cancers like prostate cancer, breast cancer, glioblastoma, colon cancer, and cervical cancer.…”

Section: Introductionmentioning

confidence: 99%

Green synthesis of hyaluronic acid coated, thiolated chitosan nanoparticles for CD44 targeted delivery and sustained release of Cisplatin in cervical carcinoma

et al. 2023

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Cervical carcinoma is one of the most prevalent gynecological cancers throughout the world. Cisplatin is used as first line chemotherapy for treatment of cervical cancer, but it comes with plethora of side effects. The aim of this study was to develop hyaluronic acid coated, thiolated chitosan nanocarriers using green synthesis approach, for CD44 targeted delivery and sustained release of Cisplatin in cervical cancer cells. After synthesis through ionic gelation method, Zeta analysis showed that the nanoparticle size was 265.9 nm with a zeta potential of +22.3 mV and .226 PDI. SEM and TEM analysis confirmed the spherical shape and smooth surface of nanoparticles. FTIR and XRD showed the presence of characteristic functional groups, successful encapsulation of drug, and crystalline nature of nanoparticles respectively. Drug loading and entrapment efficiency were calculated to be 70.1% ± 1.2% and 45% ± .28% respectively. Analysis of in vitro drug release kinetics showed that drug release followed the Higuchi model at pH 6.8 and 7.4 and Cisplatin release for up to 72 h confirmed sustained release. In vitro analysis on cervical cancer cells HeLa and normal cervical epithelial cells HCK1T was done through cell morphology analysis, trypan blue assay (concentration range of 10–80 μg/ml), and MTT cytotoxic assay (concentration range of 10–90 μg/ml). The results showed a higher cytotoxic potential of HA coated, thiolated chitosan encapsulated Cisplatin (HA-ThCs-Cis NP) nanoformulation as compared to pure Cisplatin in HeLa while in HCK1T, pure Cisplatin showed much higher toxicity as compared to HA-ThCs-Cis nanoformulation. These findings suggest that CD44 targeted delivery system can be a useful approach to minimize offtarget toxicities, give sustained release and better cellular uptake in cancer cells.

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Co‐delivery of oncolytic virus and chemotherapeutic modality: Vincristine against prostate cancer treatment: A potent viro‐chemotherapeutic approach

Anjum,

Naseer,

Ahmad

et al. 2024

Journal of Medical Virology

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Prostate cancer is a prevalent carcinoma among males, and conventional treatment options are often limited. Cytotoxic chemotherapy, despite its drawbacks, remains a mainstay. We propose a targeted co‐delivery approach using nanoscale delivery units for Oncolytic measles virus (OMV) and vincristine (VC) to enhance treatment efficacy. The HA‐coated OMV + VC‐loaded TCs nanoformulation is designed for targeted oncolytic activity in prostate cancer. The CD44 expression analysis in prostate cancer cell lines indicates a significantly high expression in PC3 cells. The optimization of nanoformulations using Design of Expert (DOE) is performed, and the preparation and characterization of HA‐coated OMV + VC‐loaded TCs nanoformulations are detailed showing average particle size 397.2 ± 0.01 nm and polydispersity index 0.122 with zeta potential 19.7 + 0.01 mV. Results demonstrate successful encapsulation efficiency with 2.4 × 106 TCID50/Ml and sustained release of OMV and VC from the nanoformulation for up to 72 h. In vitro, assays reveal potent anticancer activity at 10 ± 0.71% cell viability in PC3 cells compared to 73 ± 0.66% in HPrEC and significant morphological changes at 90 µg/ml in dose and time‐dependent manner. The co‐formulation showed positive cell death 49.5 ± 0.02% at 50 µg PI/ml in PBS and 54.3% cell cycle arrest at the G2/M phase, 8.1% G0/G1 and 5.7% at S phase, with significant mitochondrial membrane potential (MMP) at 50 µg/ml, as assessed by flow cytometry (FACS). The surface‐integrating ligand approach enhances the targeted delivery of the oncolytic virus and chemotherapeutic drug, presenting a potential alternative for prostate cancer treatment and suggested that co‐administering VC and OMV in a nanoformulation could improve therapeutic outcomes while reducing chemotherapeutic drug doses.

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Formulation of surface-functionalized hyaluronic acid-coated thiolated chitosan nano-formulation for the delivery of vincristine in prostate cancer: A multifunctional targeted drug delivery approach

Cited by 20 publications

References 37 publications

Formulation for the Targeted Delivery of a Vaccine Strain of Oncolytic Measles Virus (OMV) in Hyaluronic Acid Coated Thiolated Chitosan as a Green Nanoformulation for the Treatment of Prostate Cancer: A Viro-Immunotherapeutic Approach

Formulation for the Targeted Delivery of a Vaccine Strain of Oncolytic Measles Virus (OMV) in Hyaluronic Acid Coated Thiolated Chitosan as a Green Nanoformulation for the Treatment of Prostate Cancer: A Viro-Immunotherapeutic Approach

Green synthesis of hyaluronic acid coated, thiolated chitosan nanoparticles for CD44 targeted delivery and sustained release of Cisplatin in cervical carcinoma

Co‐delivery of oncolytic virus and chemotherapeutic modality: Vincristine against prostate cancer treatment: A potent viro‐chemotherapeutic approach

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