Generative design of large-scale fluid flow structures via steady-state diffusion-based dehomogenization.

A computationally efficient dehomogenization technique was developed based on a bioinspired diffusion-based pattern generation algorithm to convert an orientation field into explicit large-scale fluid flow channel structures. Due to the transient nature of diffusion and reaction, most diffusion-based pattern generation models were solved in both time and space. In this work, we remove the temporal dependency and directly solve a steady-state equation. The steady-state Swift-Hohenberg model was selected due to its simplistic form as a single variable equation and intuitive parameter setting for pattern geometry control. Through comparison studies, we demonstrated that the steady-state model can produce statistically equivalent solutions to the transient model with potential computational speedup. This work marks an early foray into the use of steady-state pattern generation models for rapid dehomogenization in multiphysics engineering design applications. To highlight the benefits of this approach, the steady-state model was used to dehomogenize optimized orientation fields for the design of microreactor flow structures involving hundreds of microchannels in combination with a porous gas diffusion layer. A homogenization-based multi-objective optimization routine was used to produce a multi-objective Pareto set that explored the trade-offs between flow resistance and reactant distribution variability. In total, the diffusion-based dehomogenization method enabled the generation of 200 unique and distinctly different microreactor flow channel designs. The proposed dehomogenization approach permits comprehensive exploration of numerous bioinspired solutions capturing the full complexity of the optimization and Swift-Hohenberg design space.

Microring-based programmable coherent optical neural networks.

Coherent programmable integrated photonics circuits have shown great potential as specialized hardware accelerators for deep learning tasks, which usually involve the use of linear matrix multiplication and nonlinear activation components. We design, simulate and train an optical neural network fully based on microring resonators, which shows advantages in terms of device footprint and energy efficiency. We use tunable coupled double ring structures as the interferometer components for the linear multiplication layers and modulated microring resonators as the reconfigurable nonlinear activation components. We then develop optimization algorithms to train the direct tuning parameters such as applied voltages based on the transfer matrix method and using automatic differentiation for all optical components.

Techno-economic feasibility analysis of an extreme heat flux micro-cooler.

An estimated 70% of the electricity in the United States currently passes through power conversion electronics, and this percentage is projected to increase eventually to up to 100%. At a global scale, wide adoption of highly efficient power electronics technologies is thus anticipated to have a major impact on worldwide energy consumption. As described in this perspective, for power conversion, outstanding thermal management for semiconductor devices is one key to unlocking this potentially massive energy savings. Integrated microscale cooling has been positively identified for such thermal management of future high-heat-flux, i.e., 1 kW/cm2, wide-bandgap (WBG) semiconductor devices. In this work, we connect this advanced cooling approach to the energy impact of using WBG devices and further present a techno-economic analysis to clarify the projected status of performance, manufacturing approaches, fabrication costs, and remaining barriers to the adoption of such cooling technology.

Is local methotrexate therapy effective in the treatment of cesarean scar pregnancy? A retrospective cohort study.

AIM: To evaluate the success of local methotrexate (MTX) treatment, the side-effect profile and its fertility effect in patients diagnosed with cesarean scar pregnancy. MATERIALS: This retrospective cohort study included 56 cesarean scar pregnancy patients who applied to Erciyes University Faculty of Medicine, Department of Obstetrics and Gynecology between January 2012 and January 2022 and were treated with ultrasound-guided local MTX. The results of 56 patients with cesarean scar pregnancy who underwent transvaginal ultrasound-guided single-dose local MTX treatment were evaluated. First, the contents of the sac were aspirated, and then 50 mg of MTX was injected into the gestational sac. RESULTS: The median gestational age at diagnosis was 7 weeks 2 days. The mean beta human chorionic gonadotrophin level was 31 345 ± 37 838 (range: 113-233 835 mIU/mL). Fifty-four patients were successfully treated with local MTX therapy. The interval between the first MTX injection and the normalization of beta human chorionic gonadotrophin was 55.2 ± 41.0 days. None of our patients required surgical treatment. Beta human chorionic gonadotrophin values did not decrease in one patient and she was treated with systemic MTX. Local MTX therapy could not be applied to one patient for technical reasons. Only one patient needed blood transfusion after local MTX. Thirteen patients become pregnant after treatment (76%). No systemic side effects related to MTX were observed in any of the patients. CONCLUSION: Transvaginal ultrasound-guided single-dose local MTX treatment is an effective, safe, and fertility-preserving treatment method for cesarean scar pregnancy.

A novel hardmask-to-substrate pattern transfer method for creating 3D, multi-level, hierarchical, high aspect-ratio structures for applications in microfluidics and cooling technologies.

This letter solves a major hurdle that mars photolithography-based fabrication of micro-mesoscale structures in silicon. Conventional photolithography is usually performed on smooth, flat wafer surfaces to lay a 2D design and subsequently etch it to create single-level features. It is, however, unable to process non-flat surfaces or already etched wafers and create more than one level in the structure. In this study, we have described a novel cleanroom-based process flow that allows for easy creation of such multi-level, hierarchical 3D structures in a substrate. This is achieved by introducing an ultra-thin sacrificial silicon dioxide hardmask layer on the substrate which is first 3D patterned via multiple rounds of lithography. This 3D pattern is then scaled vertically by a factor of 200-300 and transferred to the substrate underneath via a single shot deep etching step. The proposed method is also easily characterizable-using features of different topographies and dimensions, the etch rates and selectivities were quantified; this characterization information was later used while fabricating specific target structures. Furthermore, this study comprehensively compares the novel pattern transfer technique to already existing methods of creating multi-level structures, like grayscale lithography and chip stacking. The proposed process was found to be cheaper, faster, and easier to standardize compared to other methods-this made the overall process more reliable and repeatable. We hope it will encourage more research into hybrid structures that hold the key to dramatic performance improvements in several micro-mesoscale devices.

Dienogest reduces endometrioma volume and endometriosis-related pain symptoms.

This study aimed to evaluate the efficacy and adverse effects of dienogest for the treatment of endometriomas. Dienogest (2 mg/day) was administered to patients with endometrioma continuously through the 6-month study period. The patients were prospectively examined on the efficacy and side effects at baseline, at third months, and sixth months of the treatment. Twenty-four out of 30 patients were able to complete the study. The mean volume of the endometrioma decreased significantly from 112.63 ± 161.31 cm³ at baseline to 65.47 ± 95.69 cm³ at a 6-month follow-up (-41%) (p = .005). The VAS score for pelvic pain decreased significantly from 7.50 to 3.00 (p < .001) at the sixth months of treatment. The most common side effects were menstrual irregularities. Laboratory parameters did not change during the study. Dienogest considered being effective for 6 months of use in decreasing the size of endometrioma, reducing endometriosis-associated pain with a favourable safety and tolerability profile.Impact statementWhat is already known on this subject? Laparoscopic excisional surgery for endometrioma is currently the most valid approach in the treatment of endometriomas. However, there are concerns about ovarian reserve damage during surgery.What do the results of this study add? Dienogest considered being effective in decreasing the size of endometrioma, reducing endometriosis-associated pain with a favourable safety and tolerability profile. Long-term use of dienogest in younger patients with endometriomas who are yet to give birth may reduce the possibility of surgery by reducing the size of the endometriomas and may preserve ovarian reserve.What are the implications of these findings for clinical practice and/or further research? Dienogest may reduce the incidence of infectious complications such as pelvic abscess after oocyte retrieval and the surgical procedures in infertile patients with endometrioma.

Use of infragluteal folds as a full-thickness skin graft donor site for construction of the neovagina in cases of Mullerian agenesis.

AIM: The aims of this study were to present the results of using infragluteal folds as a skin graft donor site in cases of Mullerian agenesis undergoing full-thickness skin graft vaginoplasty and to evaluate the outcomes of the surgical technique. METHODS: Demographics and clinical parameters of 24 consecutive Mullerian agenesis patients refusing any dilatational procedure and undergoing neovaginal construction using infragluteal folds skin grafts from May 2004 to July 2015 were analyzed. RESULTS: The mean age of the patients was 21.5 ± 5.7 years. Five patients had nonfunctional rudimentary uterus, one patient had unilateral ovarian agenesis, one patient had unilateral renal agenesis, and one had undergone a previous vaginoplasty. There were no serious complications needing surgical or medical intervention. The depth of the neovagina in patients with a follow-up period of more than 6 months (n = 17) varied from 7 to 12 cm. Of these patients, the sexually active ones (n = 8) did not complain of dyspareunia or vaginal dryness during sexual intercourse. The resulting scars were satisfactory and acceptable for all patients. CONCLUSION: It has been our practice to use infragluteal folds as a skin graft donor site for full-thickness skin graft vaginoplasty. We believe that the results of this study demonstrate that this area is versatile and an excellent alternative to the groins and lower abdomen. Further clinical and histomorphological investigations are necessary for strong statements and results.

Comparison of systemic and local methotrexate treatments in cesarean scar pregnancies: time to change conventional treatment and follow-up protocols.

OBJECTIVE: The aim of this study was to compare the use of systemic and local methotrexate in the treatment of cesarean scar pregnancy. STUDY DESIGN: In this retrospective cohort study, we collected the data of 44 patients with cesarean scar pregnancy. The patients were grouped according to treatment modality: Group 1, local methotrexate injection (n=17) and Group 2, systemic methotrexate (n=27). The groups were compared with respect to side effects, recovery time, reproductive outcome, and treatment cost. RESULTS: The mean gestational age at diagnosis (6.4±0.93 vs. 5.4±0.80 weeks, p=0.001), pretreatment serum ß-human chorionic gonadotrophin level [27,970 (11,010-39,421) vs. 7606 (4725-16,996) mIU/mL, p=0.001], and lesion size (2.74±1.36 and 1.28±0.55cm, p=0.001) were higher in Group 1. All patients were cured by primary therapy without additional surgery. The mean times for ß-human chorionic gonadotrophin normalization, the uterine-mass disappearance, were significantly shorter in Group 1 than in Group 2 (6.17±1.55 vs. 8.11±2.0 weeks, p=0.001 and 10.47±4.14 vs. 13.40±4.44 weeks, p=0.002, respectively). The cost of treatment was similar between groups (281.133±112.123$ vs. 551.134±131.792$, p=0.76). The total pregnancy rates were not different between groups (5/16, 31.4% vs. 6/11, 54.6%, p=0.301). One recurrent cesarean scar pregnancy occurred after systemic methotrexate. Oral ulcers, the most common side effect, were seen in seven patients in Group 2. CONCLUSION: Even though treatment success and reproductive outcomes are similar, local methotrexate is superior to systemic methotrexate with regard to recovery time, side effects, and treatment costs, even in patients with unfavorable pretreatment prognostic predictors.

Acute intestinal obstruction due to a non-involuted uterus after cesarean section: case report.

The involution of the uterus is influenced by a number of factors such as advanced childbearing age, electrolyte disturbances, multiparity, repeated cesarean sections, and vaginal infections. The authors report the management of a clinical case of a 41-year-old female who presented with acute intestinal obstruction due to a non-involuted uterus after cesarean section.

Serum biochemical markers of central nerve system damage in children with acute elemental mercury intoxication.

OBJECTIVE: Acute mercury intoxication among children can occur through unintentional exposure, and neurotoxicity is one of the main findings in acute exposures. In this study, we aimed to study the central nerve system markers, namely neuron-specific enolase (NSE), S100B, and glutamate receptor (GRIA 1) levels and discuss the mechanisms of central nerve system damage and whether these parameters could be used as markers of acute elemental mercury intoxication neurotoxicity. MATERIALS AND METHODS: This is a case-control study which includes 169 children with acute elemental mercury intoxication, who were exposed to mercury in the school laboratory from a broken jar, and 45 sex- and age-matched controls without mercury exposure. Patient group were divided into three subgroups according to the neurological examination performed during the admission. Neuropathy Group included the children with neurological symptoms including peripheral neuropathy and decreased muscle strength (n = 39) (with or without dilated pupils). Dilated Pupil Group included the children who had mid-dilated/dilated pupils (n = 52). Asymptomatic Exposure Group included the children who did not have any neurological symptoms (n = 78). Serum NSE, S100B, GRIA 1, blood, and urine mercury levels were determined. RESULTS: NSE, S100B, GRIA 1, and blood mercury levels were significantly higher in exposed group than the nonexposed subjects (Median values NSE 22.4 ng/mL, 17.2 ng/mL; S100B 0.09 ng/mL, 0.08 ng/mL; GRIA 1 70.6 pg/mL, 54.1 pg/mL, and blood mercury 15.2 µg/L, 0.23 µg/L for exposed and nonexposed groups, respectively). GRIA 1 levels found to differ between exposed and nonexposed groups and it has also been found to be increased in the subgroups with positive neurological findings compared to that in neurological finding negative groups. S100B levels were found to be increased in exposed and having neurological symptom groups. There was not a significant difference between exposed-not having neurological symptom patients and control group. NSE levels were found to be higher in all subgroups when compared to those in controls, however there was not a significant difference between the subgroups. CONCLUSION: Serum NSE, GRIA 1, and S100B were increased with mercury exposure. GRIA 1 and S100B levels were observed to have the power to discriminate neurological symptom positive and negative groups. The increase in S100B levels are thought to be protecting the neurons and preventing further NSE elevations.

Increased serum interleukin-33 levels in patients with Graves' disease.

OBJECTIVE: Interleukin-33 (IL-33), a 30 kDa cytokine, is a member of IL-1 family. It is considered to be an autoimmune biomarker associated with T helper 2 (Th 2) response. γ-interferon is also produced by T helper 1 (Th 1) cells to induce cellular responses. γ-interferon is a 143-amino acid residue glycoprotein with several biological functions including potent anti-viral activity, stimulation of macrophage activity, modulation of Major Histocompatibilty Complex class I/class II expression, and regulation of a diversity of specific immune responses. The aim of this study was to investigate the serum levels of IL-33 and γ-interferon in different thyroid disorders. METHODS: Twenty patients with Graves' disease, 21 patients with Hashimoto hypothyroidism, 21 euthyroid Hashimoto patients, and 27 control subjects were recruited to this study. Blood samples were drawn and IL-33 and γ-interferon tests were analyzed from 89 participants. Serum IL-33 and γ-interferon analyses were performed by enzyme-linked immunosorbent assay. RESULTS: There was no statistically significant difference between groups for serum γ-interferon levels. Serum IL-33 concentrations were significantly higher in Graves' disease group compared to the other groups (p<0.000) There was a positive correlation between serum IL-33 and free triiodothyronine (fT3) and thyroxine (fT4). Also, negative correlation between serum IL-33 and thyroid-stimulating hormone (TSH) was statistically significant (p<0.000). CONCLUSIONS: The correlation of serum IL-33 with thyroid hormone levels may be a useful indicator for Graves' disease. These findings may help to make evident the pathophysiologic processes of the autoimmune thyroid diseases and improve therapeutic methods. .

Management of hepatic artery aneurysms.

BACKGROUND: Hepatic artery aneurysm (HAA) is a rare clinical entity that can lead to potentially life threatening complications. We reported our personal experience of 4 cases, in which we used different procedures. METHODS: The first case had a pseudo-aneurysm involving the right hepatic artery. The second case had a pseudo-aneurysm, which was localized distal to the accidentally ligated right hepatic artery from the previous cholecystectomy operation. The third case had multiple aneurysms with accompanying dissecting abdominal aortic aneurysm. The fourth case had a pseudo-aneurysm originating from the proper hepatic artery. A covered stent was successfully placed in the case 1. In the second case, the right hepatic artery was ligated distal to the aneurysm. In the third case, vascular structures were not appropriate for vascular reconstruction, and a covered stent placement and embolization were unsuccessful. In the fourth case, ligation of the proper hepatic artery and cholecystectomy was performed. RESULTS: The third case with multiple aneurysms died from multi-organ failure due to sepsis. The remaining cases (case 1, 2, and 4) are disease free and alive. CONCLUSION: HAAs are more commonly observed clinical entities, and their treatment should be handled for each patient separately. Computerized tomography-Angiography and intraoperative Doppler ultrasound are useful radio-diagnostics for determination of aneurysm and planning the operative procedure (Fig. 5, Ref. 15).

Removal of ascites up to 7.5 liters on one occasion and 45 liters in total may be safe in patients with severe ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) is a serious and potentially lethal complication of ovulation induction. We report herein a case with OHSS treated by serial vaginal paracentesis. A 31-year-old patient was hospitalized due to severe OHSS after in vitro fertilization (IVF)-embryo transfer. Transvaginal drainage was performed with a standard 17-gauge IVF needle connected to a vacuum pump through a drainage set in nine courses. We removed 45 liters of ascitic fluid in total and 7.5 liters of ascitic fluid in one course, leading to improvement of the patient's condition and laboratory parameters. In conclusion, removal of ascites up to 7.5 liters on one occasion and 45 liters in total by serial vaginal paracentesis may be performed in patients with severe OHSS.

Plasma viscosity, an early cardiovascular risk factor in women with subclinical hypothyroidism.

OBJECTIVE: It is controversial, if subclinical hypothyroidism increases cardiovascular risk. Plasma viscosity is a hemorheological parameter, which is accepted as an early cardiovascular risk factor. We investigated the alterations in plasma viscosity in women with subclinical hypothyroidism. DESIGN: 40 female patients with subclinical hypothyroidism and 31 age- and weight-matched healthy women were included. Free thyroxine (FT4), thyroid stimulating hormone (TSH), lipid parameters, fibrinogen, C-reactive protein (CRP) levels, hematocrit and plasma viscosity were measured in all subjects. MAIN OUTCOME: Plasma viscosity, total cholesterol and low density lipoprotein were significantly increased and high density lipoprotein was significantly decreased in patients with subclinical hypothyroidism. No significant correlation was found among the parameters. CONCLUSION: Increased plasma viscosity in patients' group suggests that cardiovascular risk might be increased in patients with subclinical hypothyroidism. As far as we could reach, this is the first study concerning plasma viscosity in subclinical hypothyroidism.

Role of plasma viscosity and plasma homocysteine level on hyperinsulinemic obese female subjects.

Obesity is associated with atherosclerotic risk factors, including reduced blood flow, endothelial dysfunction, lipid disorders and hyperinsulinemia. In recent years, several studies have demonstrated that elevated homocysteine is a risk factor for atherosclerosis. This study was aimed at determining whether any relationship between plasma viscosity and homocysteine levels in patients with normo and hyperinsulinemic obese patients. Obese women (n=75) and healthy, age-matched non-obese women (n=70) was included in our study. Plasma viscosity, tHcy, insulin level, total-C, LDL-C, HDL-C, triglyceride and glucose level were significantly higher in obese subjects than in non-obese subjects. Obese subjects were also divided into two groups, according to the basal insulin levels as normo and hyper insulinemic. Hyperinsulinemic obese subjects had significantly higher PV level compared with normoinsulinemic subjects. When correlation analyses were performed normoinsulinemic obese subjects, significant correlations were found between PV and total-C (r: 0.776) and insulin level (r: 0.752), BMI (r: 0.580), HOMA-IR (r: 0.510). PV was positively correlated with total-C (r: 0.485), insulin level (r: 0.624), BMI (r: 0.624) and HOMA-IR ratio (r: 0.707), in hyperinsulinemic obese subjects. Hcy was positively correlated BMI in both groups. In conclusion that, it is point out that elevated homocysteine and increased PV are two factors that may act separately and probably do not affect each other.

Bladder weight in perimenopausal women aged 50-55.

This study aimed to determine whether the preliminary factor for the manifestation of lower urinary tract symptoms (LUTS) in perimenopausal women is age-dependent morphological changes in the bladder or hypoestrogenism. The bladder weights and the effects of bladder weight changes on LUTS were evaluated in three groups of women within and age range of 50-55 years: premenopausal (n = 29), short-term menopausal (less than 5 years) (n = 38) and long-term menopausal (5 years and more) (n = 31). The comparison of LUTS among the groups was made using the International Prostate Symptom Score (IPSS) questionnaire; the ultrasonographically determined bladder weights of all the women and the duration of menopause were evaluated for the presence of any correlation for their ages. The relation between the bladder weights and the symptom scores was also tested. The bladder weight of women with longer duration of menopause was found to be significantly decreased compared with that of women with shorter-duration menopause within the same age group (p < 0.05). There was significant correlation between the increased duration of menopause and the decrease in the bladder weight (r = 0.2, p = 0.015). When all the women were taken into account, there was no correlation between the ages and bladder weights (r = 0.03; p = 0.76). There was no significant difference among the groups in terms of symptom scores evaluated as single scores, total symptom scores, total irritative and obstructive scores (p > 0.05 for each). The symptom scores had no correlation with the bladder weights or the ages of patients (p > 0.05 for each). In this age group of women the duration of hypoestrogenism does not seem to cause a difference in the symptom scores. To observe a possible significant difference, it is necessary to evaluate older women or women with a longer duration of hypoestrogenism. These findings suggest the cause for the decreased bladder weight to be the higher duration of hypoestrogenism rather than the older age.

Plasma viscosity as a cardiovascular risk marker in patients with proteinuria.

Plasma viscosity is a major determinant of capillary blood flow. It has been suggested that alteration in plasma viscosity contributes to impaired blood flow and to increased cardiovascular risk. The aim of this study was to investigate the plasma viscosity levels and its possible role in the cardiovascular risk in patients with low grade nephrotic proteinuria. 20 patients with low-grade nephrotic proteinuria (mean age: 35+/-5 years) and 20 healthy controls (mean age: 33+/-4 years) were participated in the study. Plasma viscosity was measured by Harkness capillary viscometer. Biochemical analysis were measured by commercial enzymatic kits. Plasma viscosity, plasma levels of creatinine, fibrinogen and triglyceride were increased in patients with proteinuria than in the healthy controls (p<0.001, p<0.001, p<0.001, and p<0.001, respectively). The plasma levels of total protein and albumin were significantly lower in patients with low grade nephrotic proteinuria than in healthy controls (p<0.001 and p<0.001, respectively). Plasma viscosity was negatively correlated with plasma albumin (r= -0.835, p<0.001) and total protein (r= -0.862, p<0.001) in proteinuric patients. When the correlation analyses were performed a significant positive correlation was found between plasma viscosity and fibrinogen (r=0.636, p<0.001). In the stepwise multiple regression analysis plasma viscosity was found to be related with plasma total protein (t= -6.456, p<0.001) in the patients. When the stepwise multiple regression analysis were performed in healthy controls, the significant relationship was only found between plasma viscosity and fibrinogen (t= +2.202, p<0.01). These results suggested that altered plasma composition associated with low-grade nephrotic proteinuria may be involving the determination of plasma viscosity. Thus, the plasma viscosity in patients with low-grade nephrotic proteinuria may have a prognostic value in assessing cardiovascular risk in this group.

Impaired plasma viscosity via increased cholesterol levels in peripheral occlusive arterial disease [correction of disase].

The aim of this study was to investigate the relationship between plasma viscosity and lipoprotein and apolipoprotein pattern in normo- and hypercholesterolemic patients with peripheral occlusive arterial disease (POAD). 40 patients with POAD have been selected (8 females and 32 males, mean age: 54+/-3.2 years) with clinically evident superficial femoral occlusive artery disease. They were separated into two groups as normocholesterolemic (plasma total cholesterol <200 mg/dl) and hypercholesterolemic (plasma total cholesterol >200 mg/dl). Plasma total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides, total protein, and albumin levels were determined by enzymatic methods using commercial kits. Levels of apolipoprotein AI (apo AI), and apolipoprotein B (apo B) were measured using a immunoturbidometric method. Plasma viscosity (PV) was measured by capillary viscometer. Classifying the patients with PAOD according to the cholesterol levels; hypercholesterolemic (mean total-cholesterol: 227.90+/-26.97 mg/dl) patients had significantly higher LDL-C, PV and triglyceride levels compared with nornocholesterolemic patients (p<0.001, p<0.001, p<0.001, respectively). HDL-C and apo B were significantly lower in hypercholesterolemic patients than in normocholesterolemic patients (p<0.001, p<0.001, respectively). PV was positively correlated with total cholesterol (r=0.485, p<0.05), atherogenic index (r=0.624, p<0.01), total-C/HDL-C ratio (r=0.624, p<0.05), and LDL-C/HDL-C ratio (r=0.707, p<0.001) in hypercholesterolemic patients with POAD. PV was higher in hypercholesterolemic patients with POAD than in normocholesterolemic patients with POAD. We suggest that POAD patients should be regarded as a heterogenous group with lipid and lipoprotein parameters in order to assess the microcirculation in the affected limb. In case of dyslipidemia in POAD patients an elevated plasma viscosity should be considered as coexisting risk factor.

Formulation and in vitro/in vivo evaluation of terbutaline sulphate incorporated in PLGA (25/75) and L-PLA microspheres.

Terbutaline sulphate (TBS) is widely used in the treatment of bronchial asthma, chronic bronchitis and emphysema. Because of its short biological half life and dosing schedule, a long acting TBS formulation is required to improve patient compliance. The objective of this study was to develop a TBS containing biodegradable microsphere formulation. Poly(D,L-lactide-co-glycolide) (PLGA) and poly(L-lactic acid) (L-PLA) were chosen as matrix materials. A solvent evaporation method was used for preparation of microspheres. Surface morphology, particle size distribution and encapsulation efficiency were investigated. In vitro release studies were performed in pH 7.4 phosphate buffer. In vitro distribution of microspheres were studied in the Swiss albino male mice. All microspheres were spherical in shape and had a porous surface with mean diameters of 9-21 microm. The encapsulation efficiency was influenced by the polymer type, but not the molecular weight. About 90% of the initial amount was trapped in PLGA microspheres, and the remainder was on the surface. In the case of L-PLA, 50% of the total drug was associated with the surface of microspheres. The In vitro release pattern was biphasic characterized by an initial burst phase followed by a slower phase. The L-PLA microspheres released approximately 92% of the initial payload in 72 h. On the other hand, TBS release was increased with an increase in the molecular weight of PLGA. Biodistribution of L-PLA microspheres was characterized by an initially high uptake (35%) by the lungs. All these results suggest that L-PLA and PLGA microspheres have the potential to be used for passive lung targeting.