Biomedical subjects
Publications and source records attributed to A G Andreopoulos.
The great importance of controlled release for the delivery of a variety of bioactive agents is evidenced by an increasing number of patents and commercial products that employ this technology. This article reviews the different controlled-release systems and their operating mechanisms.
The controlled release of two drugs, i.e. the sodium salt of diclofenac and propranolol was studied, by using low molecular weight D,L-Poly(lactic acid) as a matrix. Tablets of the above polymer containing those drugs were immersed into buffers with various pH values and delivery was recorded as a function of time, via UV-spectroscopy. The results showed that the polymer is appropriate for such biomedical applications, as generally, it ensures complete drug delivery within 45-60 days, which is acceptable for most cases. On the other hand, the release rate depends on many parameters including the interactions among drug, matrix and the surrounding liquid, which adds complexity to the process and requires careful investigation for proper design of a controlled release system.
Poly(D,L-Lactide) of high molecular weight (Mv) was prepared by ring-opening bulk polymerization of D,L-Lactide and characterized in terms of Mv, melting point and swelling behavior in buffer solution. Samples of the polymers with low and high Mv (2000 and 22 000 respectively) loaded with various amounts of salicylic acid (SA) were immersed in a buffer solution and the release of SA was recorded. The results obtained showed that swelling of the poly(D,L-Lactide) samples obeyed Fick's law, especially for those with high molecular weight, where biodegradation proceeds slowly. The release of SA seemed to follow a simplified relationship which is linear with time, at least for the early stages of delivery. The extent of linearity is dependent on the content of the acidic SA, which probably accelerates decomposition of the high molecular weight products.
STATEMENT OF PROBLEM: The ultimate goal of denture repair is to restore the denture's original strength and avoid further fracture. The best materials and methods for repair have not been conclusively determined. PURPOSE: This study investigated the fracture force, deflection at fracture, and toughness of a heat-polymerized denture base material repaired with heat-polymerized resin, autopolymerized resin alone, or autopolymerized resin with glass fiber or wire reinforcement. MATERIAL AND METHODS: Eight groups were evaluated: 6 with autopolymerized resin repairs, 1 with heat-polymerized resin repairs, and a control group of intact specimens. The 6 autopolymerized resin groups included 1 group with no reinforcement, 1 treated with microwave irradiation after polymerization, 2 with monolayer or multilayer glass fiber reinforcement, and 2 with round or braided wire reinforcement. Each group consisted of 12 specimens. The experimental specimens were cut, and a 3-mm butt joint gap was repaired as indicated by the group assignment. A 3-point bending test was used to determine the fracture force, deflection at fracture, and toughness of the specimens. The data were analyzed with 1-way analysis of variance and the Tukey post-hoc test (alpha=.05). RESULTS: The fracture force (28.4 to 73.4 N), deflection (1.6 to 3.8 mm), and toughness (0.02 to 0.13 J) values for all repaired groups were significantly lower than those for the control group (82.79 N, 4.4 mm, and 0.16 J, respectively), with one exception: the mean fracture force of specimens reinforced with round wire (102.9 N). Failure mode was always adhesive, meaning that fracture occurred between the denture base and repair resin. CONCLUSION: Among the repair treatments tested, the most effective was microwave-irradiated, autopolymerized resin reinforced with round wire or monolayer glass fiber ribbon.
The effect of powder packing and porosity of specimens on the swelling properties of polymeric materials was studied, in various swelling liquids, such as distilled water and 0.1 N hydrochloric acid solution. Capsules, tablets and films of hydroxypropyl methylcellulose, poly(ethylene oxide) and sodium alginate were prepared, and their weight uptake after immersion into the above solutions was recorded as a function of time, in order to assess the swelling process. Measurements of some characteristics of the as-received powders were also performed in an attempt to classify the specimens prepared according to their porosity. Within the experimental conditions of this work, it was shown that the porosity of polymeric specimens is a dominant factor that controls their swelling behaviour. Increased porosity leads to fast initial rates of weight uptake and high extent of equilibrium swelling. On the other hand, dissolution and possible degradation of polymers susceptible to acid hydrolysis results in some variations from the above mentioned behaviour. With respect to the application in controlled release systems, the overall delivery rate from a polymeric specimen is expected to be a function of both swelling and disintegration characteristics of a specimen, and therefore, the weight uptake can be considered a measure of the release only in the case of polymers with low water solubility and increased stability to hydrolysis.
The effect of powder packing and porosity of specimens on the swelling properties of polymeric materials was studied, in various swelling liquids, such as distilled water and 0.1 N hydrochloric acid solution. Capsules, tablets and films of hydroxypropyl methylcellulose, poly(ethylene oxide) and sodium alginate were prepared and their weight uptake after immersion into the above solutions was recorded as a function of time, in order to assess the swelling process. Measurements of some characteristics of the as received powders were also performed as an attempt to classify the specimens prepared according to their porosity. Within the experimental conditions of this work, it was shown that the porosity of polymeric specimens is a dominant factor that controls their swelling behaviour. Increased porosity leads to fast initial rates of weight uptake and high extent of equilibrium swelling. On the other hand, dissolution and possible degradation of polymers susceptible to acid hydrolysis, results in some variations from the above-mentioned behaviour. With respect to the application in controlled release systems, the overall delivery rate from a polymeric specimen is expected to be a function of both swelling and disintegration characteristics of a specimen and, therefore, the weight uptake can be considered a measure of the release only in the case of polymers with low water solubility and increased stability to hydrolysis.
Systems based on xanthan gum matrix containing 1%, 2% and 5% salicylic acid were prepared and studied as controlled release devices. Swelling of the matrix in distilled water and buffer solutions showed that the ionic strength of the liquid has a strong effect on the sorptive properties of the matrix. From the release experiments, conducted in distilled water at 37 +/- 0.5 degrees C, it was found that the drug delivery process was accomplished within the first 10 hours after immersion and salicylic acid was always released via a non-Fickian transport. The phenomenon can be described by a release exponent (n) in the area of 0.77 independently of the initial concentration of salicylic acid in the xanthan matrix. These results can be interpreted taking into consideration the dimensional and physical changes of the polymeric matrix during swelling.
STATEMENT OF PROBLEM: Facial prostheses worn over an extended time are exposed to various environmental factors, including sebaceous oils (sebum) and perspiration. PURPOSE: This study investigated the physical properties of tensile strength and modulus, elongation, tear strength, hardness, weight, and color change, of a silicone facial elastomer after immersion for 6 months in simulated sebum and perspiration at 37 degrees C. MATERIAL AND METHODS: Specimens made of Episil silicone elastomer were immersed in simulated alkaline or acidic perspiration as well as in sebum. Tensile and tear tests were conducted according to ISO specifications no. 37 and 39, respectively, in a Monsanto testing machine. Shore A hardness measurements were run according to ASTM D 2240. Weight changes were followed at 5, 15, 30, and 180 days, and color changes were determined in the CIE LAB system using a tristimulus colorimeter. RESULTS: An improvement of mechanical properties for specimens immersed in acidic perspiration was attributed to facilitation of the propagation of cross-linking reaction during aging of the silicone samples. Some weight increase was observed for the specimens immersed into the aqueous solution, whereas for those immersed in sebum, weight loss was recorded, probably because of extraction of some compounds. In this latter case, the color change was lower than that corresponding to simulated perspiration. CONCLUSION: The silicone specimens aged for a period, which simulates 1.5 years of clinical service, showed minimal changes with respect to the properties studied.
A new biodegradable delivery system based on poly(lactic acid) has been formulated, with potential applications in sustained antibiotic release against bone infection. The in vitro release of a new quinolone (pefloxacin) from low molecular weight poly(D,L-lactic acid) Mw = 2 x 10(3) lasted for 56 d whereas the in vivo delivery lasted 33 d. In both cases, the release rate is controlled by the drug diffusion and the polymer degradation, which seems to be the predominant factor. For the release experiments, discs were prepared from poly (D,L-lactide) Mw = 2 x 10(4) with drug loadings of 2% and 10% w/w. It was concluded that pefloxacin concentration remains higher than the Minimum Inhibitory Concentration (MIC) against the major causative bacteria of bone infection. The results indicate that the two different types of poly(lactic acid) can be used effectively in an implantable antibiotic release system.
The effect of an ampholytic surfactant on the swelling properties of polymeric materials was studied, using various swelling liquids. Tablets were prepared consisting of hydroxypropyl methylcellulose, poly(oxyethylene) and sodium alginate. Tego betain was the non-ionic surfactant used as an additive in a series of samples made of the above polymers. Those tablets were immersed in distilled water, phosphate buffer and 0.1 N HCl, and their weight uptake was recorded as a function of time, in order to assess the swelling process. Measurements of the contact angle of the above systems were also carried out for estimating their wetting properties. The results of this study showed a selectivity among polymers, surfactant and surrounding liquid. Clearly, an enhancement of the swelling capacity of hydroxypropyl methylcellulose tablets due to the surfactant was recorded. An unclear effect was observed in the case of poly(oxyethylene), whereas for sodium alginate, the dominant factor is its water solubility that controls swelling behaviour.
Poly(D,L lactic acid) was prepared by bulk polymerization of D,L lactide, both under atmospheric pressure and in vacuum. The obtained polymeric products were characterized in terms of molecular weight, Mw, melting point, calorimetric response and swelling behaviour. All products were amorphous. Their molecular weights were determined by viscosimetry and ranged from 2x10(3) to 9x10(4). Similarly, the melting points ranged from 90 to 210 degrees C. Swelling experiments, with specimens immersed in buffer solutions, showed that hydrolytic degradation started in a few days for the low Mw material, whereas for the higher molecular weight products it took much longer and probably followed a two-stage mechanism. This study suggests that the high molecular weight material could be an interesting carrier for the preparation of controlled release products, in cases where prolonged delivery is necessary.
Biomedical silicone elastomers have been studied for their potential application as carriers for controlled release of drugs, since these materials display a unique combination of properties, which might be favorable to the above use. A two component silicone gel system was used and various cross-linker ratio was applied, in order to produce networks with varying crosslink density. Swelling experiments in toluene were run in order to evaluate the network characteristics. The silicone elastomer was loaded with salicylic acid and propranolol hydrochloride and their delivery in distilled water was followed. The results showed that release is almost of zero order for high loading of salicylic acid, while delivery seems to be diffusion controlled up to a certain limit. The administered drug concentrations are relatively low if silicone discs are used, due to the hydrophobic nature of this material. On the other hand, when membranes are used with a thickness of 0.1-0.2 mm, then the delivery rate is much higher depending of course on the hydrophilic character of the drug.
Hydrogels were prepared from 2-hydroxyethyl methacrylate and ethylene glycol dimethacrylate as cross-linking agent. Two different polymerization techniques were followed, namely bulk polymerization initiated by dibenzoyl peroxide and solution polymerization, in water, using a redox initiator system. Differences in the water desorption from swollen samples between the two types of the above products were recorded and attributed to the fact that those hydrogels were obtained in glassy or rubbery state, according to the polymerization technique. Also, the delivery of salicylic acid from samples of the above types was studied, and a faster release with higher ultimate delivery was displayed by the solution polymerization hydrogels.
Compounds of a silicone elastomer suitable for preparing maxillofacial prostheses, reinforced with various amounts of silica powder, have been studied for their mechanical response and wetting properties in terms of contact angle. Tensile strength and elongation at break showed an increase with increasing silica volume fraction up to 35%, whereas the Young modulus displayed small dependence on the silica content and the resistance to tear increased continuously with filler volume fraction (Vf). The wetting properties assessed via the contact angle, seemed to degrade with increasing silica Vf, but a dependence on the elastomer network density has also been recorded.
The fracture of acrylic resin dentures is an unresolved problem in prosthodontics. In this study one brand of denture base acrylic resin was used to make specimens in the form of strips and maxillary denture bases. The specimens were cut and repaired with one type of an autopolymerizing adhesive resin and metal wires. The mechanical properties of the repaired specimens were measured, and the efficiency of each method was evaluated. The statistical results of this study revealed that geometric characteristics of a maxillary denture combined with the shape and pretreatment of reinforcement were the controlling factors for the overall mechanical behavior. Furthermore this study revealed that data with clinical significance can only be obtained by testing specimens similar to the original items used in dental practice.
The effect of various treatments on the properties of an acrylic matrix was studied, in terms of its swelling properties in buffer solution. The release of two types of drugs from those matrices and their bioadhesive character were also considered. Calcium stearate and sodium lauryl sulfate were used as additives for the matrix treatment. 2-Hydroxyethyl methacrylate was also used as a reactive agent for the acrylic resin treatment. The main function of the above chemicals is the modification of the hydrophilic/hydrophobic character of the matrix. This investigation showed that controlled release systems can be designed by adjusting the matrix properties via additives or chemical reaction.
A new biodegradable delivery system based on low molecular weight poly(lactic acid) has been formulated, with potential application in the sustained antibiotic release against bone infection. The in vitro release of two new quinolones (ofloxacin and ciprofloxacin) from the biodegradable matrix showed that the delivery of ofloxacin from the matrix lasted fifty-six days, whereas that of ciprofloxacin lasted fifty-one days. In both cases, release is controlled by the drug diffusion and the matrix degradation, the latter being the most critical factor. The obtained concentration levels are well above the Minimum Inhibitory Concentration (MIC) against the major causative bacteria of osteomyelitis. This fact in combination with the good reproducibility of measurements indicated that the system studied could be of value for the preparation of implantable controlled release systems for treatment of diseases in the bone system.
The release of newer quinolones (such as pefloxacin, ofloxacin, and ciprofloxacin) from biodegradable poly(D, L lactic acid) has been investigated. The in vitro study showed that drug delivery takes place for about two months and a maximum in concentration was recorded after fifteen days. The release from poly(lactic acid) slabs seemed to give high drug doses that are adequate for the treatment of infections caused by common pathogens.