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Evaluation of in-vitro cytotoxic effect of 5-FU loaded-chitosan nanoparticles against spheroid models

Manuscript ID: MS18-0909 | Status: under review

Purpose: The studies investigate the anticancer activity of 5-fluorouracil (5-FU)-hyaluronidase (Hase) enzyme-loaded chitosan nanoparticles (5-FUChnps) using threedimensional (3D) spheroid HCT-116 culture. Hase-loaded nanoparticles have recently been used to improve the efficacy of chemotherapeutic drugs for cancer treatment. It is found that the administration of Hase would lead to the increase of tumor vessel densities and effective vascular areas, resulting in increased perfusion inside the tumor.

Methods: Particle size and zeta potential were determined using a particle size analyzer while Fourier transform infrared (FTIR) was used to investigate the interactions among the various components making up the chitosan nanoparticles. Cytotoxic effects of 5-FU and 5FUchnps against dimensional (2D) and 3D spheroid cultures were assessed using trypan blue assay.

Results: The low molecular weight chitosan (ChiL) nanoparticle size ranged from approximately 215 to 670 nm while medium molecular weight chitosan (ChiM) nanoparticle size ranged from 151 to 778 nm. All the 5FUChnps exhibited a positive zeta potential ranging from 4 to 37 mV. Among the 16 formulations prepared, formulation #7 (5-FUChnps7) was selected for the in-vitro cytotoxic studies based on its high 5-FU entrapment efficiency (59%). 5FUchnps treated 3D HCT-116 culture exhibited significant growth inhibition compared with 5FU treated groups. Further, spheroids with significant growth inhibition exhibited high spheroid volume and non-spherical shapes.

Conclusion: 5-FUchnps were more cytotoxic to the 3D HCT-116 cultures than the free 5-FU. Study established that 5FUchnps can be potential carriers for 5-FU delivery to cancer cells.


Medical Sciences


Smoking-Mediated Macrophage Reprogramming: Mechanistic Insights and Therapeutic Implications

Manuscript ID: MS18-0907 | Status: under review

Macrophages, the mature form of the monocytes, play a significant role in tissue homeostasis and immunity. In response to environmental cues, they can undergo classical or alternative activation, polarizing into specialized functional subsets. A common hallmark of the pathologic environment is represented by smoking. Although the contribution of cigarette smoke to various cellular processes has been extensively studied, its roles in macrophage polarization have been conflicting. This review discusses the molecular and functional differences of smoke-exposed macrophages that exist between pro-inflammatory and anti-inflammatory states. We also highlight the most recent advances in therapeutic potential of targeting signaling molecules associated with smoking to modulate macrophage plasticity and polarized activation.


Medical Sciences


Effects of Bronchopulmonary Dysplasia on Swallow:Breath Interaction And Phase of Respiration with Swallow During Nonnutritive Suck

Manuscript ID: MS18-0905 | Status: under review

Objectives: This study describes swallow:breath interaction (SwBr) and phase of respiration (POR) during nonnutritive suck (NNS) in infants with bronchopulmonary dysplasia (BPD).

Methods: Logistic regression models were used to describe SwBr and POR in 43 infants with BPD. Infants were randomized to receive speech therapy (BPDwithTX) or standard care (BPDnoTX). Results were compared to a low-risk preterm infants (LRP) control group.

Results: In BPDnoTX, Obstructive Apnea (OA) occurred less with advancing gestational age (GA). In BPDwithTX, Central Apnea (CA) occurred less with advancing weeks before-first nipple feeding (WBFN) and more often with GA.

In BPDnoTX, more swallows occurred at Beginning Expiration (BE) with advancing Postmenstrual Age (PMA). Fewer swallows occurred at Apnea (AP) with increasing PMA. For BPDwithTX, fewer swallows occurred at BE with male gender and advancing PMA and more occurred with increasing weeks post-first nipple feed (WPFN). Swallows occurred more frequently at End-Expiration in males. More swallows occurred at AP with increasing WPFN and PMA.

Comparing both BPD groups to LRP, there were no differences for SwBr or POR. Speech Therapy did not affect the progression of SwBr or POR in infants with BPD. Conclusion: SwBr was not different in infants with BPD compared to LRP infants. Minor differences were noted in POR between the two groups. Speech therapy had no effect.

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