Renewable poly(δ-decalactone) based block copolymer micelles as drug delivery vehicle: in vitro and in vivo evaluation

Polymers from natural resources are attracting much attention in various fields including drug delivery as green alternatives to fossil fuel based polymers. In this quest, novel block copolymers based on renewable poly(δ-decalactone) (PDL) were evaluated for their drug delivery capabilities and compared with a fossil fuel based polymer i.e. methoxy-poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-b-PCL). Using curcumin as a hydrophobic drug model, micelles of PDL block copolymers with different orientation i.e. AB (mPEG-b-PDL), ABA (PDL-b-PEG-b-PDL), ABC (mPEG-b-PDL-b-poly(pentadecalactone) and (mPEG-b-PCL) were prepared by nanoprecipitation method. The size, drug loading and curcumin stability studies results indicated that mPEG-b-PDL micelles was comparable to its counterpart mPEG-b-PCL micelles towards improved delivery of curcumin. Therefore, mixed micelles using these two copolymers were also evaluated to see any change in size, loading and drug release. Drug release studies proposed that sustained release can be obtained using poly(pentadecalactone) as crystalline core whereas rapid release can be achieved using amorphous PDL core. Further, mPEG-b-PDL micelles were found to be non-haemolytic, up to the concentration of 40?mg/mL. In vivo toxicity studies on rats advised low-toxic behaviour of these micelles up to 400?mg/kg dose, as evident by histopathological and biochemical analysis. In summary, it is anticipated that mPEG-b-PDL block copolymer micelles could serve as a renewable alternative for mPEG-b-PCL copolymers in drug delivery applications.     

Calcium phosphate formation and ion dissolution rates in silica gel-PDLLA composites

Sol-gel derived silicas are potential biomaterials both for tissue regeneration and drug delivery applications. In this study, both SiO(2) and calcium and phosphate-containing SiO(2) (CaPSiO(2)) are combined with poly-(DL-lactide) to form a composite. The main properties studied are the ion release rates of biologically important ions (soluble SiO(2) and Ca(2+)) and the formation of bone mineral-like calcium phosphate (CaP) on the composite surface. These properties are studied by varying the quality, content and granule size of silica gel in the composite, and porosity of the polymer. The results indicate that release rates of SiO(2) and Ca(2+) depend mostly on the formed CaP layer, but in some extent also on the granule size of silicas and polymer porosity. The formation of the bone mineral-like CaP is suggested to be induced by a thin SiO(-) layer on the composite surface. However, due to absence of active SiO(2) or CaPSiO(2) granules on the outermost surface, the suitable nanoscale dimensions do not contribute the nucleation and growth and an extra source for calcium is needed instead. The result show also that all composites with varying amount of CaPSiO(2) (10-60 wt%) formed bone mineral-like CaP on their surfaces, which provides possibilities to optimise the mechanical properties of composites.     

The long-term effect of systemic tetracycline used as an adjunct to non-surgical treatment of advanced periodontitis

AIM: In the present study both the short- and the long-term effects were evaluated of a treatment that, during the phase of basic therapy, included administration of systemic tetracycline and non-surgical intervention. MATERIAL AND METHODS: 35 adult human subjects with advanced periodontitis, 19 females and 16 males, aged between 24 and 60 years, were included in a test group. 80 age- and sex-matched adult periodontitis subjects were recruited for a control group (42 females and 38 males). A baseline examination included assessment of the following parameters: number of teeth, plaque, bleeding on probing, probing attachment level, probing pocket depth. In radiographs, the distance between the cemento-enamel junction and the alveolar bone crest was determined at all interproximal sites. The subjects were given oral hygiene instruction. The members of the test group were provided with tablets with 250 mg of tetracycline hydrochloride and were instructed to take 1 tablet 4x per day for a period of 3 weeks. No antibiotic was given to the subjects in the control group. During the 3-week interval, all participants received 4-6 sessions of non-surgical periodontal therapy. All subjects were subsequently enrolled in a maintenance care program and were provided with supportive periodontal therapy (SPT) 3-4x per year. Clinical re-examinations were performed after 1, 3, 5 and 13 years. RESULTS: The present investigation demonstrated that tetracycline administered during a 3-week period concomitant with non-surgical treatment enhanced the outcome of mechanical therapy. At the re-examination 1 year after active therapy, there was in the test group an average gain in probing attachment that was almost 3x higher than the gain that occurred in an age and sex matched Control group. Re-examinations after 3, 5, and 13 years of SPT disclosed that this short-term benefit was not maintained in the longer perspective. CONCLUSION: The beneficial effect of systemically administered tetracycline on probing attachment level occurred in the first year post-therapy. Annual rates of probing attachment level change from 1 to 13 years did not differ between groups.     

Metabolic fates in humans of linamarin in cassava flour ingested as stiff porridge.

Insufficiently processed products from cassava roots may contain residual amounts of cyanogenic glucosides, mainly linamarin. The fate of orally ingested linamarin was studied following a meal of cassava porridge prepared from cassava flour from southern Tanzania with 82 mg cyanide equivalents (3035 micromol) of linamarin per kg dry weight. Following ingestion of amounts of porridge containing 243-571 micromol linamarin by 15 healthy adults a mean (range) of 21% (1-47%) of the linamarin ingested was excreted in the urine within 24 hours and a mean of 1% in the next 24 hours. Serum thiocyanate, the main cyanide metabolite, increased in all subjects from a mean (+/-SD) of 34+/-26 to 78+/-28 micromol/litre (P < 0.001). In a second group of seven subjects we found that the ingestion of porridge with a mean (range) of 431 micromol (203-669%) of linamarin resulted in a mean linamarin excretion of 127 micromol/litre and an excess thiocyanate excretion of 118 micromol/litre and that 216 micromol was unaccounted for. We conclude that less than one-half of orally ingested linamarin is converted to cyanide and hence thiocyanate, about one-quarter is excreted unchanged and another quarter is metabolized into an as yet unknown compound.     

Cyanide concentrations in blood after cigarette smoking, as determined by a sensitive fluorimetric method

Using the sensitive fluorimetric method described here, we evaluated the determination of blood cyanide as a method for monitoring exposure to tobacco smoke. The mean concentration of cyanide in blood from eight nonsmokers was 0.098 (SD 0.036) mumol/L. The concentration of cyanide in blood of smokers who had refrained from smoking for at least 2 h before sampling peaked immediately after the subjects smoked a cigarette, then rapidly declined, with a half-life of about 4 min. Its rapid disappearance from blood makes cyanide an unsuitable marker of exposure to tobacco smoke. Because the ability of patients with hepatic dysfunction to detoxify cyanide has been presumed to be impaired, we monitored the concentrations of cyanide in the blood of four patients with severe hepatic insufficiency who smoked a cigarette. The rate of elimination of cyanide from blood after smoking was only slightly less in these patients than in the controls, and the difference was not statistically significant.     

Foreign field hospitals in the recent sudden-onset disasters in Iran, Haiti, Indonesia, and Pakistan

INTRODUCTION: Foreign field hospitals (FFHs) may provide care for the injured and substitute for destroyed hospitals in the aftermath of sudden-onset disasters. PROBLEM: In the aftermath of sudden-onset disasters, FFHs have been focused on providing emergency trauma care for the initial 48 hours following the sudden-onset disasters, while they tend to be operational much later. In addition, many have remained operational even later. The aim of this study was to assess the timing, activities, and capacities of the FFHs deployed after four recent sudden-onset disasters, and also to assess their adherence to the essential criteria for FFH deployment of the World Health Organization (WHO). METHODS: Secondary information on the sudden-onset disasters in Bam, Iran in 2003, Haiti in 2004, Aceh, Indonesia in 2004, and Kashmir, Pakistan in 2005, including the number of FFHs deployed, their date of arrival, country of origin, length of stay, activities, and costs was retrieved by searching the Internet. Additional information was collected on-site in Iran, Indonesia, and Pakistan through direct observation and key informant interviews. RESULTS: Basic information was found for 43 FFHs in the four disasters. The first FFH was operational on Day 3 in Bam and Kashmir, and on Day 8 in Aceh. The first FFHs were all from the militaries of neighboring countries. The daily cost of a bed was estimated to be US$2,000. The bed occupancy rate generally was < 50%. None of the 43 FFHs met the first WHO/Pan-American Health Organization (PAHO) essential requirement if the aim is to provide emergency trauma care, while 15% followed the essential requirement if follow-up trauma and medical care is the aim of deployment. DISCUSSION: A striking finding was the lack of detailed information on FFH activities. None of the 43 FFHs arrived early enough to provide emergency medical trauma care. The deployment of FFHs following sudden-onset disasters should be better adapted to the main needs and the context and more oriented toward substituting for pre-existing hospitals, rather than on providing immediate trauma care.     

Initial outcome and long-term effect of surgical and non-surgical treatment of advanced periodontal disease

AIM: A clinical trial was performed to determine (i) the initial outcome of non-surgical and surgical access treatment in subjects with advanced periodontal disease and (ii) the incidence of recurrent disease during 12 years of maintenance following active therapy. MATERIAL AND METHODS: Each of the 64 subjects included in the trial showed signs of (i) generalized gingival inflammation, (ii) had a minimum of 12 non-molar teeth with deep pockets (> or =6 mm) and with > or =6 mm alveolar bone loss. They were randomly assigned to 2 treatment groups; one surgical (SU) and one non-surgical (SRP). Following a baseline examination, all patients were given a detailed case presentation which included oral hygiene instruction. The subjects in SU received surgical access therapy, while in SRP non-surgical treatment was provided. After this basic therapy, all subjects were enrolled in a maintenance care program and were provided with meticulous supportive periodontal therapy (SPT) 3-4 times per year. Sites that at a recall appointment bled on gentle probing and had a PPD value of > or =5 mm were exposed to renewed subgingival instrumentation. Comprehensive re-examinations were performed after 1, 3, 5 and 13 years of SPT. If a subject between annual examinations exhibited marked disease progression (i.e., additional PAL loss of > or =2 mm at > or =4 teeth), he/she was exited from the study and given additional treatment. RESULTS: It was observed that (i) surgical therapy (SU) was more effective than non-surgical scaling and root planing (SRP) in reducing the overall mean probing pocket depth and in eliminating deep pockets, (ii) more SRP-treated subjects exhibited signs of advanced disease progression in the 1-3 year period following active therapy than SU-treated subjects. CONCLUSION: In subjects with advanced periodontal disease, surgical therapy provides better short and long-term periodontal pocket reduction and may lead to fewer subjects requiring additional adjunctive therapy.     

Gas‐foamed poly(lactide‐co‐glycolide) and poly(lactide‐co‐glycolide) with bioactive glass fibres demonstrate insufficient bone repair in lapine osteochondral defects

Deep osteochondral defects may leave voids in the subchondral bone, increasing the risk of joint structure collapse. To ensure a stable foundation for the cartilage repair, bone grafts can be used for filling these defects. Poly(lactide‐co‐glycolide) (PLGA) is a biodegradable material that improves bone healing and supports bone matrix deposition. We compared the reparative capacity of two investigative macroporous PLGA‐based biomaterials with two commercially available bone graft substitutes in the bony part of an intra‐articular bone defect created in the lapine femur. New Zealand white rabbits (n = 40) were randomized into five groups. The defects, 4 mm in diameter and 8 mm deep, were filled with neat PLGA; a composite material combining PLGA and bioactive glass fibres (PLGA–BGf); commercial beta‐tricalcium phosphate (β‐TCP) granules; or commercial bioactive glass (BG) granules. The fifth group was left untreated for spontaneous repair. After three months, the repair tissue was evaluated with X‐ray microtomography and histology. Relative values comparing the operated knee with its contralateral control were calculated. The relative bone volume fraction (?BV/TV) was largest in the β‐TCP group (p ≤ 0.012), which also showed the most abundant osteoid. BG resulted in improved bone formation, whereas defects in the PLGA–BGf group were filled with fibrous tissue. Repair with PLGA did not differ from spontaneous repair. The PLGA, PLGA–BGf, and spontaneous groups showed thicker and sparser trabeculae than the commercial controls. We conclude that bone repair with β‐TCP and BG granules was satisfactory, whereas the investigational PLGA‐based materials were only as good as or worse than spontaneous repair.