Public Health, Vol 2, Issue 1, Jan-Mar / Oral Biopsy in General Dental Practice: A DOI/ijmedph 2Dept of Oral Pathology & Microbiology. Oral Health for the Americas (“the Plan”) (Document CD47/14), adopted in through . Most country programs have integrated oral health care into. referred to as oral health indicators, and include dental caries experience, untreated dental decay, tooth removal FLUORIDATION OF WATER SUPPLIES.
PEEAs with different hydrophilicity were synthesized and characterized. Experiments showed that an increase in copolymer hydrophilicity gave particles less prone to cell interaction.
BSA release profiles from PEEA microspheres demonstrated that an increase in polymer hydrophilicity was useful in limiting protein burst and modulating drug delivery rate by increasing PEEA degradability.
Application and further development of chemical engineering principles for chemotherapy of cancer and other diseases. This review defines chemotherapeutic engineering as an engineering discipline that applies and further develops chemical engineering principles, techniques and devices for chemotherapy of cancer and other diseases. It provides new challenges as well as new opportunities for chemical engineering. Chemical engineering has substantially changed the human civilization through its services and products to improve the quality of life for human being.
It is now time for chemical engineering to contribute to the most important aspect of the quality of life—human health care. Cancer and cardiovascular diseases are the leading causes for deaths. Chemotherapy is one of the most important treatments currently available for cancer and other diseases such as cardiovascular diseases.
The present status of chemotherapy is far from being satisfactory. Its efficacy is limited and patients have to suffer from serious side effects, some of which are life-threatening.
Chemotherapeutic engineering is emerging to help solving the problems in chemotherapy and to eventually develop an ideal way to conduct chemotherapy with the best efficacy and the least side effects. This review gives, from an engineering point of view, brief introductions to cancer and cancer treatment, chemotherapy and the problems involved in chemotherapy, and the possible roles of chemical engineering in solving the problems involved. Progress in developing various controlled and targeted drug delivery systems is reviewed with an emphasis on nanoparticles of biodegradable polymers and lipid bilayer vesicles liposomes.
Preparation, characterization, in vitro release, cell line experiments and animal testing of drug-loaded polymeric nanoparticles are described with paclitaxel as a prototype drug, which is one of the best anticancer drugs found in nature. A novel drug delivery system, liposomes-in-microspheres, is used as an example for possible combinations of the existing polymer- and lipid-based delivery systems. Research of molecular interactions between the drug and the cell membrane is also reviewed, with the lipid monolayer at the air—water or oil—water interface and bilayer vesicles as models for the cell membrane.
Finally, mathematical modeling in chemotherapeutic engineering is discussed with typical examples in the literature. This review is a short introduction of chemotherapeutic engineering to chemical engineers, biomedical engineers, other engineers, clinical oncologists, and pharmaceutical scientists, who are interested in developing new dosage forms of drugs for chemotherapy of cancer and other diseases with the best efficacy and the least side effects.
Bioadhesive characterization of poly methylidene malonate 2. The efficacy of a drug delivery system is predicated on its retention in the target tissue. Microparticle is one of the most popular and effective drug delivery configurations.
Recently, it has been shown that the interaction between drug-loaded microparticles and tissues is related to the effectiveness of paclitaxel delivery to the bladder wall of mice for treating superficial bladder cancer. In this study, the adhesive interaction between poly methylidene malonate 2. Young's modulus of single PMM 2. For plain PMM 2. The adhesion energy of PMM 2. The loading of paclitaxel in PMM 2. It is hypothesized that the electrostatic repulsion between paclitaxel and collagen at pH 4 reduces the adhesion energy of PMM 2.
This study may offer insight for design of future microparticulate delivery systems by providing the experimental and theoretical tools to study the bioadhesive interaction between drug-loaded microparticles and model extracellular matrices.
MR imaging of biodegradable polymeric microparticles: A potential method of monitoring local drug delivery. Gadolinium diethylenetriamine pentaacetic acid Gd-DTPA was encapsulated into biodegradable, bioadhesive polymeric microparticles to enable noninvasive monitoring of their local intravesical delivery with MRI. The microparticles were characterized by contrast agent encapsulation and release kinetics, T 1 relaxation rates, and contrast enhancement in vivo.
MR images showed ring-shaped regions of enhancement inscribing the bladder wall, which were attributed to the microparticles that were preferentially adherent to the mucosa lining the urothelium. The images of controls exhibited no such enhancement. Contrast enhancement was observed for at least 5 days after the initial instillation, although the enhancement decreased due to microparticle degradation or mucosa renewal. The localized distribution of biodegradable, bioadhesive microparticles encapsulating Gd-DTPA was successfully visualized with MRI in vivo, allowing particle-mediated delivery to be temporally and spatially monitored noninvasively.
Particle uptake by Peyer's patches: A pathway for drug and vaccine delivery. Particle uptake by Peyer's patches offers the possibility of tailoring vaccines that can be delivered orally. However, particle uptake by the follicle-associated epithelium in the gastrointestinal tract depends on several different factors that are the physicochemical properties of the particles, the physiopathological state of the animal, the analytical method used to evaluate the uptake and finally the experimental model.
These parameters do not allow a clear idea about the optimal conditions to target the Peyer's patches. The goal of this review is to clarify the role of each factor in this uptake. Sustained delivery of growth factors from methylidene malonate 2. The incorporation of growth factors into new methylidene malonate 2. Five growth factors were used in this study: Formulation in poly methylidene malonate 2.
Once dried, formulations could be subsequently stored at 4 or 20 degrees C or immediately subjected to degradation in conditioned cell culture medium. Toxicity of blends and their degradation products were evaluated in several cell lines with MTT.
Bioactivity and biospecificity of the formulated growth factors were investigated using MTT and immunohistochemical staining. Combined ELISA and crystal violet colorimetric assays were performed to analyze growth factors release. Limited toxicities were observed for unloaded poly methylidene malonate 2. Once optimized, growth factors formulations did not reveal lower bioactivities or loss of biospecificity. To conclude, dual growth factor delivery was made possible by the mean of poly methylidene malonate 2.
These studies demonstrate the ability of methylidene malonate 2. Poly methylidene malonate 2. Bioactivity of the released paclitaxel was confirmed by assessing cytotoxicity on MBT-2, a bladder cancer cell line. Biodistribution of particles after bladder instillation was assessed by confocal microscopy and scanning electron microscopy. The efficacy of intravesical injections of conventional and microsphere paclitaxel was assessed by histology and survival rates.
After bladder instillation the microspheres adhered to the mucosa and remained in the bladder lumen for at least 48 hours. In the BBN induced bladder cancer model compared with controls the 9-week survival rate was significantly improved by 2 injections of paclitaxel bio-adhesive microparticles. Microscopic evaluation confirmed the lower incidence of carcinoma in situ and high grade transitional cell carcinoma after injections of paclitaxel bio-adhesive microparticles compared with controls and with injections of similar doses of the conventional paclitaxel formulation.
Intravesical administration of poly methylidene malonate 2. The brain tissue response to biodegradable poly methylidene malonate 2. The aim of this study was to follow the in vivo biodegradation as well as to appreciate the brain tissue response to poly methylidene malonate 2. Ninety-three adult Sprague-Dawley female rats were engaged in the study in which 54 underwent stereotactic implantation of blank gamma-sterilized PMM 2.
Twelve rats were implanted with the same 5-fluorouracil 5-FU -loaded microspheres. Seventeen controls received the suspension medium alone carboxymethylcellulose aqueous solution. The animals were sacrificed on post-operative days 1, 2, 8 and months 1, 2, 3, 6, 9, 12, 15 and The brains were dissected, frozen, cut in a freezing microtome, and the slides were processed for immunohistological evaluation and scanning electron microscopy.
During the first few days, the moderate inflammatory response to blank or loaded PMM 2. The macrophagous-microglial reaction was similar to the one typically found following any damage in the CNS. There were also no differences in GFAP reactivity between the implanted animals and the controls. Blank microspheres began to degrade between 3 and 6 months, while 5-FU microspheres degraded between 8 days and 1 month.
The polymer degradation generated in both cases a pronounced inflammatory and immunological reaction, leading to an important cell loss, a cerebral atrophy and to the death of several animals. Biocompatible poly methylidene malonate -made materials for pharmaceutical and biomedical applications.
In the past 20 years, mainly with the sponsorship of Laboratoires UPSA France and, afterwards, its spin-off company Virsol France , several authors have studied methylidene malonate-based polymers used in drug delivery approaches and in the development of novel biomaterials. The present paper aims at summing up the preparation of methylidene malonate monomers, and essentially a novel asymmetric diester structure: Their polymeric and copolymeric derivatives and a few of their applications which were reported in the literature are also presented.
It encompasses the manufacturing of particulate systems such as nano- and macroparticles designed for the delivery of hydrophilic or hydrophobic drugs and biomolecules.
This review article also describes their use as biomaterials of interest in the fields of tissue repair, as drug reservoirs or ophthalmology, as implants. Copolymers based on these monomers offer a large range of properties and could be used as new surfactants, micellar vectors, or particulate systems for gene delivery.
Therefore, this review, certainly the first dedicated exclusively to methylidene malonate-based materials, highlights the great biomedical and pharmaceutical technology potential of these new materials. A 1-hr in vivo enzyme inhibition assay based on esterase activity has good potential for marine toxicity assessment.
A test was developed for the rotifer Brachionus plicatilis based on the nonfluorescent substrate fluorescein diacetate FDA , which is metabolized by esterases to a fluorescent product. Enzyme inhibition, as determined by reduced fluorescence, can be scored visually or quantified using a fluorometer.
The 1-hr esterase inhibition test has sensitivity comparable to that of hr rotifer acute tests for several compounds. The toxicity of six compounds was examined using the quantified assay. The resulting IC20s were within a factor of 3 of the hour LC50s. IC20 values ranged from 0. Electrophoretic analysis of rotifer homogenates suggested that a single C esterase acetylesterase was responsible for FDA metabolism in B.
Several other aquatic species are capable of metabolizing FDA, including Brachionus calyciflorus, Mysidopsis bahia, Menidia beryllina, Pimephales promelas, Ceriodaphnia dubia, Daphnia pulex, Artemia salina, and Ophryotrocha sp. The esterase inhibition test is an attractive tool for assessing aquatic toxicity because of its speed, simplicity, sensitivity, and applicability to a broad range of aquatic species. Biodegradable poly D,L-lactic acid PLA50 nanoparticles coated with either a readily digestible protein, albumin, or a non-digestible polymer, polyvinyl alcohol, were prepared by the solvent evaporation technique.
PLA50 degradation was determined using size exclusion chromatography as well as the enzymatic detection of lactate in bulk solution. In pepsin-rich simulated gastric fluid, similar behaviour was observed for both nanoparticle systems: In pancreatin-rich simulated intestinal fluid, however, the degradation of the PLA50 matrix was different, depending on the agent coating the nanoparticles: Thus, a direct relationship between degradability of the coating agent and subsequent PLA50 degradation in simulated intestinal fluid was established.
Controlled vaccine release in the gut-associated lymphoid tissues. Orally administered biodegradable microspheres target the Peyer's patches. Microspheres prepared from various polymers were evaluated for their usefulness as carriers for the targeted delivery of vaccine antigens to the gut-associated lymphoid tissues. Following oral administration to mice, microspheres consisting of polystyrene, poly methyl methacrylate , poly hydroxybutyrate , poly dl-lactide , poly l-lactide , and of poly dl-lactide-co-glycolide with various ratios of lactide to glycolide were absorbed into the Peyer's patches of the small intestine.
In contrast, no or very little uptake was observed with microspheres consisting of ethyl cellulose, cellulose acetate hydrogen phthalate or cellulose triacetate. Poly dl-lactide-co-glycolide microspheres containing a toxoid vaccine of staphylococcal enterotoxin B were prepared and characterized for their size distribution, surface morphology and toxoid release kinetics in an aqueous environment.
Oral immunization with these microspheres effectively delivered and released the vaccine in the gutassociated lymphoid tissue as determined by their ability to induce a disseminated mucosal IgA anti-toxin antibody response.
Nanoparticles as carriers for oral peptide absorption: Studies on particle uptake and fate. Previous work from our laboratories has provided quantitative proof of the importance of the gut associated lymphoid tissue GALT in the processes involved in the uptake of polystyrene nanoparticles delivered orally, and has confirmed the role of the Peyer's patches in the uptake of particles through the small intestine.
In more recent work discussed here the role of lymphoid tissue in the large intestine has been demonstrated, a significant amount of the total uptake occurring in this region of the gut. Adsorption of poloxamers and onto 50 nm polystyrene nanoparticles inhibited uptake in the small intestine and reduced uptake from the large intestine, suggesting reduction in adhesion to GALT and other epithelial tissues in the presence of the poloxamer coating but also indirectly suggesting differences in the surface characteristics of lymphoid tissue at different sites in the gut.
We have demonstrated, therefore, both an increase and a decrease in absorption of nanoparticles from the gastro-intestinal tract and some, albeit serendipitous, control of the site of uptake and absorption, which should provide pointers for the future development of systems with optimal uptake characteristics.
Uptake of PMMA nanoparticles from the gastrointestinal tract after oral administration to rats: Modification of the body distribution after suspension in surfactant solutions and in oil vehicles. The animals were sacrificed after 30 min, 1, 2, 4, 8 h, 1, and 4 days, the blood was collected, and different organs and tissues were removed.
The gastrointestinal GI -tract was separated into stomach, small intestine, and colon. The contents of those parts were collected and the remaining GI-tract sections thoroughly rinsed. The radioactivity in the above organs, tissues, and GI-tract contents were determined using a scintillation counter. The radioactivity concentrations were highest in the GI-tract content and decreased rather rapidly between 2 h and 1 day. These concentration did not correlate totally to those in the GI-tract contents.
The highest concentrations in the body were observed between 15 and 60 min but remained at considerable levels for 4 days. No significant difference appeared between saline without surfactants and peanut oil.
Binding and uptake of biodegradable poly-DL-lactide micro- and nanoparticles in intestinal epithelia. The use of biodegradable particles as oral delivery vehicles for macromolecular drugs was investigated. We evaluated the binding, uptake and absorption of poly-dl-lactide PLA micro- and nanoparticles in Caco-2 monolayers and in ileal tissue and gut associated lymphoid tissue GALT of anaesthetised rats and rabbits. Nanoparticles were found to be absorbed better than microparticles.
Overall, little discrimination in uptake patterns was evident between Peyer's patch PP and non-PP tissue while rat ileum showed a greater uptake capacity than rabbit. Our results show that uptake of PLA particles was low capacity, size-dependent and predominantly transcellular in all systems.
The affinity of PLA particles for intestinal epithelia and GALT needs to be greatly enhanced in order to achieve improved oral bioavailability of macromolecules. Evaluation of nano- and microparticle uptake by the gastrointestinal tract. Numerous papers over the last two decades have demonstrated that particle uptake by the gastrointestinal tract is a reality. In addition, polymeric nano- and microparticles have proved to be useful delivery systems to enhance oral bioavailability of poorly absorbed drugs or to induce mucosal immune response.
However, despite the amount of data available, no set criteria are available for the design of a good particulate carrier for oral delivery of peptides or antigens. This is partly due to the publication of conflicting and confusing data. The source of discrepancy is actually multiparametric e. The purpose of this review is to discuss the advantages and the limitations of the methodologies and the models used to evaluate gastrointestinal uptake of nano- and microparticles.
To study the uptake of biodegradable microparticles in Caco-2 cells. Biodegradable microparticles of polylactic polyglycolic acid co-polymer PLGA The microparticle uptake in Caco-2 cells was studied by confocal microscopy and also by quantitating the 6-coumarin content of the microparticles taken up by the cells.
The effects of microparticle concentration, and incubation time and temperature on microparticle cell uptake were also studied. The study demonstrated that the Caco-2 cell microparticle uptake significantly depends upon the microparticle diameter. Similarly in terms of number the uptake of 0. The efficiency of uptake of 0.
The Caco-2 cell microparticle 0. The uptake of microparticles increased with incubation time, reaching a steady state at two hours. In some ways, this is self-evidently true. All children, except those with specific sensory or cognitive disabilities, will learn to speak without apparently having any tuition. In contrast, many people do not become proficient writers and readers. The two kinds of language use also clearly involve different perceptual skills.
There is in addition the matter of the different ages at which speech and literacy normally develop. Until quite recently, as Olson implies, it was also commonly asserted by researchers that the two modes of speech and writing were different in their nature.
Speech is usually spontaneous and its sound fades rapidly, while writing is commonly planned and may be drafted; and as a product it may persist for centuries, and can be read and re-read many times.
It was also argued that the two modes are commonly associated with different kinds of communicative function. For these various reasons, it was concluded that the different modes necessarily require the use of rather different compositional and comprehension skills.
Again, there is certainly some truth in these claims. But in recent times the general validity of this bi-modal view of speech and writing as very distinct language modes has been questioned. Olson briefly mentions some reasons why this is so, and others can be found.
Speech can also be recorded, so it need not fade rapidly, and can be replayed for multiple hearings. Moreover, with the advent of information technology new ways of using language are emerging which make it difficult to continue to argue that the two modes are completely distinct in nature, or in the skills they require for their use. Consider, for example, the use of email, conferencing and other similar kinds of computer-based communication.
We will be looking at those kinds of language use, and at multimodal communication, in section 4.
2.1.1 Oral and literate modes
In vitro and in vivo Evaluation of Poly(Methylidene Malonate ) Microparticles Behavior for Oral Administration. Denture status 55 Intervention urgency Section 2: Oral health self- assessment Self-assessment of oral health and risks Oral. Significant oral injury will still occur in spite of preventive activities. Sports during which protective equipment for the head is worn, which may thus.