Uptake and Cytotoxicity of Docetaxel-Loaded Hyaluronic Acid-Grafted Oily Core Nanocapsules in MDA-MB 231 Cancer Cells

Purpose

It is hypothesized that docetaxel (Doc)-loaded hyaluronic acid (HA)-polyethylene glycol/poly(ε-caprolactone)-grafted oily core nanocapsules (NCs) can enhance the drug cytotoxicity and uptake in CD44 expressing breast cancer (BC) cells (MDA-MB 231).

Methods

NCs were prepared, optimized and characterized by dynamic light scattering, transmission electron microscopy (TEM), and powder X-ray diffraction (PXRD). In vitro cytotoxicity tests [MTS, level of reactive oxygen species (ROS) and level of reduced glutathione (GSH)] were performed in BC cells. The contribution of CD44 to the NCs cellular uptake was elucidated using an anti CD44 antibody blockage and a CD44 negative NIH3T3 cell line.

Results

The optimum formulation of Doc-loaded HA oily core NCs had respective mean diameter, polydispersity, and drug encapsulation efficiency of 224.18 nm, 0.32, and 60.38%. The NCs appeared spherical with low drug crystallinity, while the drug release data fitted to first order equation. Compared to that of ungrafted NCs, the cytotoxicity of Doc-loaded HA-grafted NCs was significantly enhanced (p<0.05). A decrease of the intracellular level of ROS was reversely correlated with that of GSH. Interestingly, the cellular internalization of HA-grafted NCs mediated CD44 was dramatically enhanced (3 to 4-fold) with respect to the absence of specific biomarker or targeting ligand.

Conclusions

The use of HA-grafted NCs enhanced the selective drug payload, cytotoxicity and uptake in MDA-MB 231 cells. Therefore, it could be a promising template for safe and effective delivery of Doc and similar chemotherapeutic agents in cancer cells.     

HIV voluntary counseling and testing: an experience from India

Despite proof of voluntary counseling and testing (VCT) effectiveness in HIV disease prevention and management, there are limited reports on experience with pre- and post-HIV-test counseling in developing countries. In view of this, we aimed to bring to the fore the voluntary counseling and testing experience at a tertiary healthcare center. The present study was conducted at the voluntary counseling and testing center of a tertiary healthcare center and the National HIV Reference Center. Participants were 1169 men and 581 females attending the VCT clinic from February 2005 to March 2006. Odds ratios were calculated for each of the variable to analyze the strength of association with HIV sero-status. Out of 1750 patients, 322 (27.5%) males and 156 females (26.9%) tested HIV-positive. HIV-sero-positivity was observed to be associated to participant age (approximately 1.5 for 25-44 yrs age group), marital status (2.3 times in married patients), primary or lower education level (1.5 times), citing spouse death/HIV-infected spouse as the reason for seeking VCT (2.2 times) and reporting a history of risk behavior as reason for getting tested. This study aims to evaluate the effectiveness of existing client initiated voluntary counseling and testing facility in the light of a recent recommendation by WHO/UNAIDS for the implementation of provider initiated voluntary counseling services. Through this study, we could also highlight socio-demographic factors, like education and age, and reasons stated by participants for seeking VCT, which were associated with HIV-positive status and put an individual at a higher risk of HIV infection.     

Systemic Racism: Pharmacists’ Role and Responsibility

Systemic racism is a public health emergency and disproportionately impacts communities of color, specifically Black Americans. Pharmacists took an oath to protect the welfare of humanity and protect our patients. As such, to practice truly patient-centered care, pharmacists must recognize racism as a root cause of social determinants of health and use their privilege to educate themselves and their colleagues around dismantling structural racism.     

Synergistic Approach Using Platelet‐Rich Fibrin and 1% Alendronate for Intrabony Defect Treatment in Chronic Periodontitis: A Randomized Clinical Trial

Background: Platelet‐rich fibrin (PRF) is a reservoir of concentrated platelets that provides a pool of biologic growth‐promoting factors and cytokines, which help in mediating regeneration of lost bone and soft tissue maturation. Alendronate (ALN), a member of the amino‐bisphosphonate group, is known to enhance periodontal tissue regeneration by inhibiting osteoclast‐mediated bone resorption and promoting osteoblast‐mediated osteogenesis. The current intervention aims to assess combined effectiveness of PRF and 1% ALN with access therapy in intrabony defect (IBD) treatment in patients with chronic periodontitis (CP). Methods: Single IBDs in 90 patients were categorized into three groups: 1) group 1 had access therapy alone; 2) group 2 had access therapy with PRF; and 3) group 3 had access therapy with PRF + 1% ALN. Site‐specific plaque index, modified sulcus bleeding index, probing depth (PD), clinical attachment level (CAL), and gingival marginal level, included as parameters for clinical assessment, were evaluated before surgery at baseline and 9 months postoperatively. Percentage IBD depth reduction, assessed using radiographs, was evaluated at baseline and postoperatively. Results: Compared with groups 1 and 2, group 3 exhibited significantly greater reduction in PD and gain in CAL postoperatively. Significantly greater IBD depth reduction was shown in group 3 (54.05% ± 2.88%) compared with group 2 (46% ± 1.89%) and group 1 (7.33% ± 4.86%) postoperatively. Conclusion: Combined approach therapy of PRF + 1% ALN for IBD treatment in patients with CP showed better clinical parameter outcomes with greater IBD depth reduction compared with PRF and access therapy alone.     

Correlation of oxidative status with BMI and lung function in COPD

OBJECTIVES: The imbalance in oxidative status together with nutrition depletion and low body weight play a vital role in the pathogenesis and severity of chronic obstructive pulmonary disease (COPD). The study was undertaken to ascertain if a relationship existed between oxidative status and BMI in COPD. In addition, association of oxidative status and BMI with lung function of the disease was also examined. MATERIALS AND METHODS: In 202 COPD patients and 136 healthy controls plasma lipid peroxidation (LPO), reduced glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT) activities, BMI and FEV(1)% predicted were looked for interactions. RESULTS: The patients had increased LPO (p=0.006) and decreased antioxidants (GSH, p=0.005; GPx, p=0.035 and CAT, p=0.008, respectively). Of note are the correlations of oxidative stress markers with BMI and FEV(1)% predicted in the patients. LPO inversely and GSH, GPx, and CAT positively correlated with both BMI (p=0.007, p<0.001, p=0.045 and p=0.009, respectively), and FEV(1)% of predicted (LPO, p=0.001; GSH, p<0.001; GPx, p=0.043 and CAT, p<0.001) in the patients. Further, a positive correlation existed between BMI and FEV(1)% predicted (p=0.016) in COPD. CONCLUSION: The intimate relationship of oxidative status with BMI and lung function, and the direct correlation between BMI and FEV(1) may potentiate severity of the disease.     

Nanoparticle-based topical ophthalmic formulation for sustained release of stereoisomeric dipeptide prodrugs of ganciclovir

Poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles (NP) of Val-Val dipeptide monoester prodrugs of ganciclovir (GCV) including L-Val-L-Val-GCV (LLGCV), L-Val-D-Val-GCV (LDGCV) and D-Val-L-Val-GCV (DLGCV) were formulated and dispersed in thermosensitive PLGA-PEG-PLGA polymer gel for the treatment of herpes simplex virus type 1 (HSV-1)-induced viral corneal keratitis. Nanoparticles containing prodrugs of GCV were prepared by a double-emulsion solvent evaporation technique using various PLGA polymers with different drug/polymer ratios. Nanoparticles were characterized with respect to particle size, entrapment efficiency, polydispersity, drug loading, surface morphology, zeta potential and crystallinity. Prodrugs-loaded NP were incorporated into in situ gelling system. These formulations were examined for in vitro release and cytotoxicity. The results of optimized entrapment efficiencies of LLGCV-, LDGCV- and DLGCV-loaded NP are of 38.7?±?2.0%, 41.8?±?1.9%, and 45.3?±?2.2%; drug loadings 3.87?±?0.20%, 2.79?±?0.13% and 3.02?±?0.15%; yield 85.2?±?3.0%, 86.9?±?4.6% and 76.9?±?2.1%; particle sizes 116.6?±?4.5, 143.0?±?3.8 and 134.1?±?5.2?nm; and zeta potential ?15.0?±?4.96, ?13.8?±?5.26 and ?13.9?±?5.14?mV, respectively. Cytotoxicity studies suggested that all the formulations are non-toxic. In vitro release of prodrugs from NP showed a biphasic release pattern with an initial burst phase followed by a sustained phase. Such burst effect was completely eliminated when NP were suspended in thermosensitive gels with near zero-order release kinetics. Prodrugs-loaded PLGA NP dispersed in thermosensitive gels can thus serve as a promising drug delivery system for the treatment of anterior eye diseases.     

COX2 and p53 risk-alleles coexist in COPD

BACKGROUND: Cigarette smoke stimulates airway epithelial cells to release pro-inflammatory cytokines which influence various inflammation-related genes, including COX2, whereas p53 expression is known to alter in such a condition. Since both the genes share several common physiological functions including inflammation and oxidative stress, we investigated within gene and gene-gene interactions towards susceptibility to the disease. METHOD: In a prospective gene-association study we conducted PCR-RFLP for genotyping the COX2 -765G/C and 8473T/C and p53 72Pro/Arg polymorphisms in 229 COPD patients and 147 healthy controls. RESULTS: The -765GC+CC genotypes of COX2 and Pro/Pro+Pro/Arg genotypes of p53 were prevalent in patients with significant odds ratio, 2.05 and 2.30, respectively (p=0.001; p=0.009, respectively), as a consequence, the -765C and 72Pro alleles were prevalent (p相似文献   

Mothers' beliefs about analgesia during childhood immunization

BACKGROUND:

Immunization injections are the most common painful medical procedures experienced during childhood, yet there is a discrepancy between recommendations for the effective use of topical anesthetics to reduce vaccine injection pain and actual practice.

OBJECTIVE:

To improve our understanding of mothers’ experiences and practices regarding their children’s routine immunizations.

METHOD:

Adopting an interpretive, naturalistic paradigm, semi-structured interviews were conducted with 15 mothers to examine their perceptions and experiences of their children’s immunization pain and pain management.

RESULTS:

The findings demonstrated three main themes: attitudes toward immunization pain, immunization pain management and physicians as sources of information. Participants described feeling distressed while their children were being immunized, but most managed these difficulties by focusing on the benefits of immunization and by minimizing or justifying the pain. All of the participants used non-pharmacological techniques to manage immunization injection pain. Few mothers were aware of the availability of topical anesthetics. When participants did use pharmacological analgesic approaches, oral analgesics were most likely to be used for prophylaxis and treatment of fever, and participants were unaware of evidence-based approaches to managing pain. Participants viewed their physicians as trusted sources of information, and the majority said that they would likely use a topical anesthetic in the future if recommended or approved by their physician.

CONCLUSION:

The present findings provide direction for future knowledge translation activities to enhance the knowledge of mothers and clinicians regarding pain during immunization injections and its effective management.