Fabrication and evaluation of Eudragit® polymeric films for transdermal delivery of piroxicam

The aims of this work were to develop and characterize the prolonged release piroxicam transdermal patch as a prototype to substitute oral formulations, to reduce side effects and improve patient compliance. The patches were composed of film formers (Eudragit^®) as a matrix backbone, with PVC as a backing membrane and PEG200 used as a plasticizer. Results from X-ray diffraction patterns and Fourier transform-infrared spectroscopy indicated that loading piroxicam into films changed the drug crystallinity from needle to an amorphous or dissolved form. Piroxicam films were prepared using Eudragit^® RL100 and Eudragit^® RS100 as film formers at various ratios from 1:0 to 1:3. Films prepared solely by Eudragit^® RL100 showed the toughest and softest film, while other formulations containing Eudragit^® RS100 were hard and brittle. Drug release kinetic data from the films fitted with the Higuchi model, and the piroxicam release mechanism was diffusion controlled. Among all formulation tested, Eudragit^® RL100 films showed the highest drug release rate and the highest drug permeation flux across human epidermal membrane. Increasing drug loading led to an increase in drug release rate. Eudragit^® can be used as a film former for the fabrication of piroxicam films.     

A Therapeutic Microparticle-Based Tumor Lysate Vaccine Reduces Spontaneous Metastases in Murine Breast Cancer

Metastatic breast cancer is currently incurable, and available therapies are associated with severe toxicities. Induction of protective anti-tumor immunity is a promising therapeutic approach for disseminated breast cancer, as immune responses are (i) systemic; (ii) antigen-specific; and (iii) capable of generating long-lived “memory” populations that protect against future tumor recurrences. Pursuant with this approach, we have developed a novel heterologous prime/boost vaccination regimen that reduces spontaneous lung metastases in mice with established murine 4T1 adenocarcinoma breast tumors. In our studies, mice were orthotopically challenged with luciferase-expressing 4T1 tumor cells; luciferase expression was retained in vivo, enabling us to quantitatively track metastatic tumor growth via bioluminescent imaging. On day 6 post-challenge, mice received a therapeutic “prime” consisting of bulk tumor lysates encapsulated in poly(lactic-co-glycolic) acid (PLGA) microparticles (MPs). On day 11, mice received a “boost” composed of free tumor lysates plus a cocktail of Toll-like receptor (TLR)-stimulating adjuvants. Tumor progression was monitored in vaccinated and untreated mice for 25 days, a time at which 100% of untreated mice had detectable lung tumors. PLGA MPs injected subcutaneously trafficked to draining lymph nodes and were efficiently phagocytosed by dendritic cells (DCs) within 48 h. Our combination therapy reduced metastatic lung tumor burdens by 42% and did not induce autoimmunity. These findings illustrate that vaccines based upon MP delivery of tumor lysates can form the basis of an effective treatment for metastatic breast cancer and suggest that similar approaches may be both efficacious and well-tolerated in the clinic.KEY WORDS: breast cancer, microparticle, PLGA, tumor lysate, vaccine     

STOP-FALLING: A Simple Checklist Tool for Fall Prevention in a Nursing Facility

Falls are highly prevalent and lead to major health morbidity and mortality in older adults. We developed a “STOP-FALLING” checklist as a multifactorial intervention tool kit for a single long-term care facility. The objective of this study was to determine feasibility and adherence of the checklist, and to determine whether STOP-FALLING reduces total number of falls, frequent fallers, and fall-related injuries.This is a quality improvement demonstration project comparing the effect on falls 3 months before and 3 months after introducing a STOP-FALLING checklist. All older adult patients who lived in the long-term care unit of a single facility were included. PTs, geriatricians, and registered nurses participated in the STOP-FALLING initiative. Staff were surveyed on satisfaction by 8-item questionnaires, which were obtained 3 months after checklist implementation. Data on the rate of falls, the number of recurrent fallers, the number of minor injuries, and the number of major injuries 3 months prior and 3 months after the intervention were collected by facility fall log.A total of 32 patients were screened using the STOP-FALLING checklist. Staff survey revealed a high satisfaction rate with ≤15 minutes to complete the checklist. Data at 3 months after initiation of the checklist revealed a reduction in the fall rates (2.80-1.65 falls per person-year), number of frequent fallers (5.00-2.30/mo after), number of falls without injuries (3.00-1.67/mo), number of minor injuries (4.00-2.67/mo), and number of major injuries (0.33-0/mo).We observed excellent staff satisfaction using the STOP-FALLING checklist. Our pilot project suggests that the intervention may decrease fall rates and other fall-related injuries.     

Trend of human rabies prophylaxis in developing countries: Toward optimal rabies immunization

Rabies is a fatal infectious disease. Because prevention is the key management for rabies, many vaccination regimens have been developed and used worldwide. The aims for developing rabies vaccination regimens include decreasing the number and amount of dosages, decreasing the duration and the number of clinical visits, and reducing cost. Interestingly, some intradermal (ID) regimens have proved to be as effective as the standard intramuscular (IM) regimens, and have been increasingly used in developing countries because they are less expensive. In this article, we reviewed rabies vaccines based on results obtained from clinical trials and international treatment guidelines for post-exposure prophylaxis, pre-exposure prophylaxis for the high risk group, and booster vaccination.     

Biodegradable Microparticles Loaded with Doxorubicin and CpG ODN for In Situ Immunization Against Cancer

In situ immunization is based on the concept that it is possible to break immune tolerance by inducing tumor cell death in situ in a manner that provides antigen-presenting cells such as dendritic cells (DCs) with a wide selection of tumor antigens that can then be presented to the immune system and result in a therapeutic anticancer immune response. We designed a comprehensive approach to in situ immunization using poly(lactic-co-glycolic acid) (PLGA)-biodegradable microparticles (MPs) loaded with doxorubicin (Dox) and CpG oligodeoxynucleotides (CpG) that deliver Dox (chemotherapy) and CpG (immunotherapy) in a sustained-release fashion when injected intratumorally. Dox induces immunogenic tumor cell death while CpG enhances tumor antigen presentation by DCs. PLGA MPs allow their safe co-delivery while evading the vesicant action of Dox. In vitro, we show that Dox/CpG MPs can kill B and T lymphoma cells and are less toxic to DCs. In vivo, Dox/CpG MPs combined with antibody therapy to enhance and maintain the T cell response generated systemic immune responses that suppressed injected and distant tumors in a murine B lymphoma model, leading to tumor-free mice. The combination regimen was also effective at reducing T cell lymphoma and melanoma tumor burdens. In conclusion, Dox/CpG MPs represent an efficient and safe tool for in situ immunization that could provide a promising component of immunotherapy for patients with a variety of types of cancer.KEY WORDS: cancer vaccine, CpG, doxorubicin, in situ immunization, microparticles, PLGA     

Development of a Poly (lactic-co-glycolic acid) Particle Vaccine to Protect Against House Dust Mite Induced Allergy

Poly(lactic-co-glycolic acid) (PLGA) particles carrying antigen and adjuvant is a promising vaccine system which has been shown to stimulate systemic antigen-specific immune responses. In this study, we investigated the relationship of (i) the sizes of PLGA particle and (ii) the presence of cytosine-phosphate-guanine motifs (CpG), with the extent and type of immune response stimulated against Dermatophagoides pteronyssinus-2 (Der p2) antigen. Different sizes of PLGA particles encapsulating CpG were prepared using a double emulsion solvent evaporation method. Mice were vaccinated with Der p2 and different sizes of empty or CpG-loaded PLGA particles. Vaccinated mice were exposed to daily intranasal instillation of Der p2 for 10 days followed by euthanization to estimate leukocyte accumulation in bronchoalveolar lavage (BAL) fluids, antibody profiles, and airway hyperresponsiveness. PLGA particles showed a size-dependent decrease in the proportion of eosinophils found in BAL fluids. Mice vaccinated with the Der p2 coated on 9-μm-sized empty PLGA particles showed increased levels of IgE and IgG1 antibodies as well as increased airway hyperresponsiveness. All sizes of PLGA particles encapsulating CpG prevented airway hyperresponsiveness after Der p2 exposures. Inflammatory responses to Der p2 exposure were significantly reduced when smaller PLGA particles were used for vaccination. In addition, encapsulating CpG in PLGA particles increased IgG2a secretion. This study shows that the size of PLGA particles used for vaccination plays a major role in the prevention of house dust mite-induced allergy and that incorporation of CpG into the PLGA particles preferentially develops a Th1-type immune response.     

Screen viewing time and externalising problems in pre-school children in Northern Thailand

Objectives: There are increasing reports of younger children accessing media and screen. This study aims to describe screen use in pre-school children and its association with externalising problems.

Methods: A cross-sectional study of pre-schoolers aged two to five years was conducted. Their caregivers were asked to provide data regarding screen use by their children and themselves. The Child Behaviour Checklist (CBCL) was completed by caregivers to assess their child’s behaviour.

Results: Participants included 200 caregivers of pre-school children. There were 47% of pre-schoolers who had used at least three types of media. When comparing the 0–1, >1 to 2, and >2 hours per day of screen viewing time groups, the children who had experienced more screen time also had significantly more background media and their caregivers had more screen time (p?p?=?0.03).

Conclusion: Pre-schoolers with more screen viewing time did not have a significantly greater externalising problem score than those with less screen time. A longitudinal study with a larger sample size would provide more information.