Layer-by-layer development of chitosan/alginate-based platelet-mimicking nanocapsules for augmenting doxorubicin cytotoxicity against breast cancer.

Breast carcinoma is considered one of the most invasive and life-threatening malignancies in females. Mastectomy, radiation therapy, hormone therapy and chemotherapy are the most common treatment choices for breast cancer. Doxorubicin (DOX) is one of the most regularly utilized medications in breast cancer protocols. However, DOX has showed numerous side effects including lethal cardiotoxicity. This study aims to fortify DOX cytotoxicity and lowering its side effects via its combining with the antidiabetic metformin (MET) as an adjuvant therapy, along with its effective delivery using natural platelet-rich plasma (PRP), and newly-developed PRP-mimicking nanocapsules (NCs). The PRP-mimicking NCs were fabricated via layer-by-layer (LBL) deposition of oppositely charged biodegradable and biocompatible chitosan (CS) and alginate (ALG) on a core of synthesized polystyrene nanoparticles (PS NPs) followed by removal of the PS core. Both natural PRP and PRP-mimicking NCs were loaded with DOX and MET adjuvant therapy, followed by their physicochemical characterizations including DLS, FTIR, DSC, and morphological evaluation using TEM. In-vitro drug release studies, cytotoxicity, apoptosis/necrosis, and cell cycle analysis were conducted using MCF-7 breast cancer cells. Also, an in-vivo assessment was carried out using EAC-bearing balb/c mice animal model to evaluate the effect of DOX/MET-loaded natural PRP and PRP-mimicked NCs on tumor weight, volume and growth biomarkers in addition to analyzing the immunohistopathology of the treated tissues. Results confirmed the development of CS/ALG-based PRP-mimicking NCs with a higher loading capacity of both drugs (DOX and MET) and smaller size (259.7 ± 19.3 nm) than natural PRP (489 ± 20.827 nm). Both in-vitro and in-vivo studies were in agreement and confirmed that MET synergized the anticancer activity of DOX against breast cancer. Besides, the developed LBL NCs successfully mimicked the PRP in improving the loaded drugs biological efficiency more than free drugs.

Baicalin lipid nanocapsules for treatment of glioma: characterization, mechanistic cytotoxicity, and pharmacokinetic evaluation.

OBJECTIVES: Baicalin is a promising anticancer nutraceutical compound, but its application is hindered by its low water solubility and bioavailability, which can be remedied by its encapsulation in nanoparticles. METHODS: Lipid nanocapsules (LNCs) were developed to enhance baicalin delivery via intravenous and intranasal routes, and potentiate its therapeutic activity in treatment of glioma. RESULTS: LNCs displayed a particle size of 17.76 nm and sustained release of 74.36% after 24 h. The IC50 of baicalin LNCs (13 ± 5 µg/ml) was 60 times lower than free baicalin (780 ± 107 µg/ml) on human glioblastoma multiform cell line U87, with adequate cellular uptake as delineated by confocal laser microscopy. Both baicalin and LNCs induced cell cycle arrest at S and G2/M phases, with significant up-regulation in P21 gene, and decline in Nrf-2, HO-1 and VEGF gene expression. LNCs increased baicalin's bioavailability, either after intravenous (AUC0-24 h 10.94 ± 0.28 vs 3.53 ± 0.09 µg/ml*h), or intranasal administration (AUC0-24 h 6.26 ± 0.11 vs 3.17 ± 0.04 µg/ml*h). They also bypassed the blood brain barrier and achieved significantly higher brain delivery compared to free baicalin (drug targeting efficiency 160.73% vs 52.9%). CONCLUSION: Baicalin LNCs is a promising treatment modality for glioma, when administered through intravenous or intranasal routes.

Spinal direct current stimulation with locomotor training in chronic spinal cord injury.

Transcutaneous spinal direct current stimulation (tsDCS) is a non-invasive method of stimulating spinal circuits that can modulate and induce changes in corticospinal excitability (CE) in incomplete spinal cord injury (SCI). A double-blinded sham controlled study of 2 male patients (A and B) with SCI was carried out. Patient A received sham and cathodal tsDCS, while Patient B received sham and anodal tsDCS. Four baselines were recorded prior to each arm of stimulation. Outcomes were then measured post each arm of stimulation; 10-meter walk test, modified ashworth scale, berg balance scale, manual muscle testing, and spinal cord independence measure-III. Transcranial magnetic stimulation, assessed motor evoked potentials. Cathodal tsDCS increased the scores in few of the outcome measures and decreased others. Anodal stimulation increased scores in all measures. Motor evoked potentials increased in post-cathode and deteriorated in post-anode. In conclusion, tsDCS modulated gait parameters, spasticity, and CE in incomplete SCI.

Association of postural balance and isometric muscle strength in early- and middle-school-age boys.

OBJECTIVE: The purpose of this study was to evaluate the isometric muscle strength (IMS) and dynamic balance in early- and middle-school-age boys and to assess the strength of association between the dynamic balance scores and 6 different IMS indexes. METHODS: This is a cross-sectional study of a convenience sample of 94 boys who were 6 to 10 years of age and classified into an early school age (6-8 years) group (n = 50) and a middle school age (8-10 years) group (n = 44). Balance was tested using a Biodex Balance System. Anteroposterior Stability Index, Mediolateral Stability Index, and Overall Stability Index were recorded. IMS of 11 muscle groups was measured with a handheld dynamometer and categorized into 6 different muscle strength indices. RESULTS: The mean (SD) values of anteroposterior, mediolateral, and overall stability indexes observed for all study boys were 1.9 ± 1.0, 1.2 ± 0.7, and 2.5 ± 1.2 respectively. In the middle school age group, strong positive relationships were detected between the overall stability index and trunk, lower limb, anti-gravity, pro-gravity, and total strength indexes (r = -0.86/P < .001, r = -0.91/P < .001, r = -0.88/P < .001, r = -0.83/P < .001, and r = -0.84/P < .001 respectively), while no significant relationship was detected with the upper limb strength index (r = 0.159/P = .303). In the early school age group, moderate positive relationships were detected between the overall stability index and anti-gravity, lower limb, and total strength indexes (r = -0.404/P = .004, r = -0.356/P = .011, and r = -0.350/P = .013 respectively). CONCLUSION: Dynamic balance did not appear to be mature by the age of 10 years. Better balance skills were recorded in the mediolateral direction than in the anteroposterior direction. In the middle school age group, the overall stability index had positive relationships with almost all examined muscle strength indexes excepting the upper limb strength index.