The controlled release of drugs from emulsified, sol gel processed silica microspheres

Controlled release silica sol gels are room temperature processed, porous, resorbable materials with generally good compatibility. Many molecules including drugs, proteins and growth factors can be released from sol gels and the quantity and duration of the release can vary widely. Processing parameters render these release properties exquisitely versatile. The synthesis of controlled release sol gels typically includes acid catalyzed hydrolysis to form a sol with the molecules included. This is then followed by casting, aging and drying. Additional steps such as grinding and sieving are required to produce sol gel granules of a desirable size. In this study, we focus on the synthesis of sol gel microspheres by using a novel process with only two steps. The novelty is related to acid–base catalysis of the sol prior to emulsification. Sol gel microspheres containing either vancomycin (antibiotic) or bupivacaine (analgesic) were successfully synthesized using this method. Both drugs showed controlled, load dependent and time dependent release from the microspheres. The in vitro release properties of sol gel microspheres were remarkably different from those of sol gel granules produced by grinding and sieving. In contrast to a fast, short-term release from granules, the release from microspheres was slower and of longer duration. In addition, the degradation rate of microspheres was significantly slower than that of the granules. Using various mathematical models, the data reveal that the release from sol gel powder is governed by two distinct phases of release. In addition, the release from emulsified microspheres is delayed, a finding that can be attributed to differences in surface properties of the particles produced by emulsification and those produced by casting and grinding. The presented results represent an excellent data set for designing and implementing preclinical studies

Differential alkaline phosphatase responses of rat and human bone marrow derived mesenchymal stem cells to 45S5 bioactive glass

Bioactive glass is used as both a bone filler and as a coating on implants, and has been advocated as a potential osteogenic scaffold for tissue engineering. Rat-derived mesenchymal stem cells (MSCs) show elevated levels of alkaline phosphatase activity when grown on 45S5 bioactive glass as compared to standard tissue culture plastic. Similarly, exposure to the dissolution products of 45S5 elevates alkaline phosphatase activity and other osteogenic markers in these cells. We investigated whether human MSCs grown under the same laboratory conditions as rat MSCs would exhibit similar responses. In general, human MSCs produce markedly less alkaline phosphatase activity than rat MSCs, regardless of cell culture conditions, and do not respond to the growth factor BMP-2 in the same way as rat MSCs. In our experiments there was no difference in alkaline phosphatase activity between human MSCs grown on 45S5 bioactive glass or tissue culture plastic, in samples from five different orthopaedic patients, regardless of culture media composition. Neither was there any consistent effect of 45S5 dissolution products on human MSCs from three different donors. These results suggest that the positive effects of bioactive glass on bone growth in human patients are not mediated by accelerated differentiation of mesenchymal stem cells

Solution mediated effect of bioactive glass in poly (lactic-co-glycolic acid)-bioactive glass composites on osteogenesis of marrow stromal cells

A previous study demonstrated that the incorporation of bioactive glass (BG) into poly (lactic-co-glycolic acid) (PLGA) can promote the osteoblastic differentiation of marrow stromal cells (MSC) on PLGA by promote the formation of a calcium phosphate rich layer on its surface. To further understand the mechanisms underlying the osteogenic effect of PLGA-BG composite scaffolds, we tested whether solution-mediated factors derived from composite scaffolds/hybrids can promote osteogenesis of marrow stromal cells. The dissolution product from PLGA-30%BG scaffold stimulated osteogenesis of MSC, as was confirmed by increased mRNA expression of osteoblastic markers such as osteocalcin (OCN), alkaline phosphatase (ALP), and bone sialoprotein (BSP). The three-dimensional structure of the scaffolds may contribute to the production of cell derived factors which promoted distant MSC differentiation. Thus PLGABG composites demonstrates significant potential as a bone replacement material

REMOTE INFLUENCE OF HUMAN PHYSIOLOGY BY A RITUAL HEALING TECHNIQUE

Two experiments tested the hypothesis that remote calming effects of a traditional healing ritual can be objectively measured using indicators of electrodermal activity, heart rate and blood volume. A total of 14 sessions were conducted in the initial study and 16 sessions were conducted in the replication. In both experiments, the authors exchanged roles as experimenter, healer and patient. Healers were instructed to try to calm the remote patient using a set of traditional ritual magic strategies, or to exert no influence (as a control). The patient created a doll in his or her likeness and provided mementos, pictures and an autobiographical sketch. The healer used these materials to form a sympathetic connection with the patient who was located in another building in an isolated toom. During the experiments, there were no other connections between the healer and the patient. Each session consisted of a randomized counterbalanced sequence of five calming and five control epochs of one minute each. No performance feedback was provided to the healer or patient during the session. The combined results of both experiments showed significant effects for changes in blood volume (p = .00002), heart rate (p = .001) and electrodermal activity (p = .013), suggesting that traditional magic healing rituals caused significant relaxation of the vascular system and arousal of electrodermal activity. These rituals appear to be helpful in focusing mental intention in laboratory investigations of direct mental interactions with living systems

REMOTE INFLUENCE OF HUMAN PHYSIOLOGY BY A RITUAL HEALING TECHNIQUE

Two experiments tested the hypothesis that remote calming effects of a traditional healing ritual can be objectively measured using indicators of electrodermal activity, heart rate and blood volume. A total of 14 sessions were conducted in the initial study and 16 sessions were conducted in the replication. In both experiments, the authors exchanged roles as experimenter, healer and patient. Healers were instructed to try to calm the remote patient using a set of traditional ritual magic strategies, or to exert no influence (as a control). The patient created a doll in his or her likeness and provided mementos, pictures and an autobiographical sketch. The healer used these materials to form a sympathetic connection with the patient who was located in another building in an isolated toom. During the experiments, there were no other connections between the healer and the patient. Each session consisted of a randomized counterbalanced sequence of five calming and five control epochs of one minute each. No performance feedback was provided to the healer or patient during the session. The combined results of both experiments showed significant effects for changes in blood volume (p = .00002), heart rate (p = .001) and electrodermal activity (p = .013), suggesting that traditional magic healing rituals caused significant relaxation of the vascular system and arousal of electrodermal activity. These rituals appear to be helpful in focusing mental intention in laboratory investigations of direct mental interactions with living systems