Twin vaginal delivery: innovate or abdicate.

PubMed

Easter, Sarah Rae; Taouk, Laura; Schulkin, Jay; Robinson, Julian N

2017-05-01

Neonatal safety data along with national guidelines have prompted renewed interest in vaginal delivery of twins, particularly in the case of the noncephalic second twin. Yet, the rising rate of twin cesarean deliveries, coupled with the national decline in operative obstetrics, raises concerns about the availability of providers who are skilled in twin vaginal birth. Providers are key stakeholders for increasing rates of twin vaginal delivery. We surveyed a group of practicing obstetricians to explore potential barriers to the vaginal birth of twins with a focus on delivery of the noncephalic second twin. Among 107 responding providers, only 57% would deliver a noncephalic second twin by breech extraction. Providers who preferred breech extraction had a higher rate of maternal-fetal medicine subspecialty training (26.2% vs 4.3%; P<.01) and were more likely to be in an academic practice environment (36.1% vs 10.9%; P<.01) and to practice in high-volume centers that deliver >30 sets of twins annually (57.4% vs 34.8%; P=.02). Most providers (54.2%) were familiar with the findings from the recent randomized trial that demonstrated the safety of twin vaginal birth. However, knowledge of the trial was not associated statistically with a preference for breech extraction (62.3% vs 43.5%; P=.05). Providers who preferred breech extraction were more likely to agree with recent society guidelines that encourage the vaginal birth of twins (86.9% vs 63.0%; P<.01). In an adjusted analysis, the 46% of providers with a perceived need for more training were far less likely to prefer breech extraction for delivery of a noncephalic second twin (adjusted odds ratio, 0.38; 95% confidence interval, 0.16-0.95). Furthermore, 57% of providers who would not offer their patient breech extraction would be willing to consult a colleague for support with a noncephalic twin delivery. These results suggest that scientific evidence and society opinion are likely insufficient to reverse the national

Variation in vaginal breech delivery rates by hospital type.

PubMed

Gregory, K D; Korst, L M; Krychman, M; Cane, P; Platt, L D

2001-03-01

To relate vaginal breech delivery rates to the following hospital types: public, health maintenance organization, private teaching, or private nonteaching. In a retrospective study using administrative discharge data from Los Angeles County, California, we calculated the vaginal breech delivery rates of singleton breech deliveries during calendar years 1988 and 1991. Ten thousand four hundred breech deliveries were identified, 8988 (86.4%) term and 1412 (13.6%) preterm. Twelve percent (1252 of 10,400) were vaginal deliveries (10.1% term and 24.5% preterm). Term vaginal breech deliveries varied by hospital type and were more frequent in public hospitals (28.4%, 95% confidence interval [CI] 26.1%, 30.7%) and less frequent in private nonteaching hospitals (5.4%, 95% CI 4.8%, 5.9%). Term vaginal deliveries were 2.4 to 11.3 times more likely among black women and 1.3 to 6.3 times more likely for Hispanic women across all hospital types, compared with white women in private nonteaching hospitals. There was no difference in the proportion of preterm vaginal breech deliveries by hospital type (mean 24.5%). However, with the exception of public hospitals, the proportion of vaginal breech deliveries for both term and preterm deliveries varied significantly by ethnicity. The use of vaginal breech delivery varied by hospital type and patient ethnicity. Within private teaching and nonteaching hospitals, vaginal breech delivery was more likely for black women than for women of other ethnic groups. Further study is needed to understand the hospital policies or organizational factors, as well as the patient-related sociocultural and clinical factors, that contribute to those differences.

Sulfonate-modified phenylboronic acid-rich nanoparticles as a novel mucoadhesive drug delivery system for vaginal administration of protein therapeutics: improved stability, mucin-dependent release and effective intravaginal placement.

PubMed

Li, ChunYan; Huang, ZhiGang; Liu, ZheShuo; Ci, LiQian; Liu, ZhePeng; Liu, Yu; Yan, XueYing; Lu, WeiYue

Effective interaction between mucoadhesive drug delivery systems and mucin is the basis of effective local placement of drugs to play its therapeutic role after mucosal administration including vaginal use, which especially requires prolonged drug presence for the treatment of gynecological infectious diseases. Our previous report on phenylboronic acid-rich nanoparticles (PBNPs) demonstrated their strong interaction with mucin and mucin-sensitive release profiles of the model protein therapeutics interferon (IFN) in vitro, but their poor stability and obvious tendency to aggregate over time severely limited future application. In this study, sulfonate-modified PBNPs (PBNP-S) were designed as a stable mucoadhesive drug delivery system where the negative charges conferred by sulfonate groups prevented aggregation of nanoparticles and the phenylboronic acid groups ensured effective interaction with mucin over a wide pH range. Results suggested that PBNP-S were of spherical morphology with narrow size distribution (123.5 nm, polydispersity index 0.050), good stability over a wide pH range and 3-month storage and considerable in vitro mucoadhesion capability at vaginal pH as shown by mucin adsorption determination. IFN could be loaded to PBNP-S by physical adsorption with high encapsulation efficiency and released in a mucin-dependent manner in vitro. In vivo near-infrared fluorescent whole animal imaging and quantitative vaginal lavage followed by enzyme-linked immunosorbent assay (ELISA) assay of IFN demonstrated that PBNP-S could stay in the vagina and maintain intravaginal IFN level for much longer time than IFN solution (24 hours vs several hours) without obvious histological irritation to vaginal mucosa after vaginal administration to mice. In summary, good stability, easy loading and controllable release of protein therapeutics, in vitro and in vivo mucoadhesive properties and local safety of PBNP-S suggested it as a promising nanoscale mucoadhesive drug delivery

Vaginal breech delivery: results of a prospective registration study

PubMed Central

2013-01-01

Background Most countries recommend planned cesarean section in breech deliveries, which is considered safer than vaginal delivery. As one of few countries in the western world Norway has continued to practice planned vaginal delivery in selected women. The aim of this study is to evaluate prospectively registered neonatal and maternal outcomes in term singleton breech deliveries in a Norwegian hospital during a ten years period. We aim to compare maternal and neonatal outcomes in term breech pregnancies subjected either to planned vaginal or elective cesarean section. Methods A prospective registration study including 568 women with term breech deliveries (>37 weeks) consecutively registered at Sorlandet Hospital Kristiansand between 2001 and 2011. Fetal and maternal outcomes were compared according to delivery method; planned vaginal delivery versus planned cesarean section. Results Of 568 women, elective cesarean section was planned in 279 (49%) cases and vaginal delivery was planned in 289 (51%) cases. Acute cesarean section was performed in 104 of the planned vaginal deliveries (36.3%). There were no neonatal deaths. Two cases of serious neonatal morbidity were reported in the planned vaginal group. One infant had seizures, brachial plexus injury, and cephalhematoma. The other infant had 5-minutes Apgar < 4. Twenty-nine in the planned vaginal group (10.0%) and eight in the planned cesarean section group (2.9%) (p < 0.001) were transferred to the neonatal intensive care unit. However, only one infant was admitted for ≥4 days. According to follow-up data (median six years) none of these infants had long-term sequelae. Regarding maternal morbidity, blood loss was the only variable that was significantly higher in the planned cesarean section group versus in the vaginal delivery group (p < 0.001). Conclusions Strict guidelines were followed in all cases. There were no neonatal deaths. Two infants had serious neonatal morbidity in the planned

Vaginal delivery of breech presentation.

PubMed

Kotaska, Andrew; Menticoglou, Savas; Gagnon, Robert

2009-06-01

To review the physiology of breech birth; to discern the risks and benefits of a trial of labour versus planned Caesarean section; and to recommend to obstetricians, family physicians, midwives, obstetrical nurses, anaesthesiologists, pediatricians, and other health care providers selection criteria, intrapartum management parameters, and delivery techniques for a trial of vaginal breech birth. Trial of labour in an appropriate setting or delivery by pre-emptive Caesarean section for women with a singleton breech fetus at term. Reduced perinatal mortality, short-term neonatal morbidity, long-term infant morbidity, and short- and long-term maternal morbidity and mortality. Medline was searched for randomized trials, prospective cohort studies, and selected retrospective cohort studies comparing planned Caesarean section with a planned trial of labour; selected epidemiological studies comparing delivery by Caesarean section with vaginal breech delivery; and studies comparing long-term outcomes in breech infants born vaginally or by Caesarean section. Additional articles were identified through bibliography tracing up to June 1, 2008. The evidence collected was reviewed by the Maternal Fetal Medicine Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) and quantified using the criteria and classifications of the Canadian Task Force on Preventive Health Care. This guideline was compared with the 2006 American College of Obstetrician's Committee Opinion on the mode of term singleton breech delivery and with the 2006 Royal College of Obstetrician and Gynaecologists Green Top Guideline: The Management of Breech Presentation. The document was reviewed by Canadian and International clinicians with particular expertise in breech vaginal delivery. The Society of Obstetricians and Gynaecologists of Canada. SUMMARY STATEMENTS: 1. Vaginal breech birth can be associated with a higher risk of perinatal mortality and short-term neonatal morbidity than

Vaginal delivery - discharge

MedlinePlus

... slowly. Get plenty of rest. You can start sexual activity around 6 weeks after delivery, if the discharge or lochia has stopped. Women who breastfeed may have a lower sex drive than normal, along with vaginal dryness and pain ...

pH-sensitive Eudragit nanoparticles for mucosal drug delivery.

PubMed

Yoo, Jin-Wook; Giri, Namita; Lee, Chi H

2011-01-17

Drug delivery via vaginal epithelium has suffered from lack of stability due to acidic and enzymatic environments. The biocompatible pH-sensitive nanoparticles composed of Eudragit S-100 (ES) were developed to protect loaded compounds from being degraded under the rigorous vaginal conditions and achieve their therapeutically effective concentrations in the mucosal epithelium. ES nanoparticles containing a model compound (sodium fluorescein (FNa) or nile red (NR)) were prepared by the modified quasi-emulsion solvent diffusion method. Loading efficiencies were found to be 26% and 71% for a hydrophilic and a hydrophobic compound, respectively. Both hydrophilic and hydrophobic model drugs remained stable in nanoparticles at acidic pH, whereas they are quickly released from nanoparticles upon exposure at physiological pH. The confocal study revealed that ES nanoparticles were taken up by vaginal cells, followed by pH-responsive drug release, with no cytotoxic activities. The pH-sensitive nanoparticles would be a promising carrier for the vaginal-specific delivery of various therapeutic drugs including microbicides and peptides/proteins. Published by Elsevier B.V.

Antibiotic prophylaxis for operative vaginal delivery.

PubMed

Liabsuetrakul, Tippawan; Choobun, Thanapan; Peeyananjarassri, Krantarat; Islam, Q Monir

2017-08-05

Vacuum and forceps assisted vaginal deliveries are reported to increase the incidence of postpartum infections and maternal readmission to hospital compared to spontaneous vaginal delivery. Prophylactic antibiotics may be prescribed to prevent these infections. However, the benefit of antibiotic prophylaxis for operative vaginal deliveries is still unclear. To assess the effectiveness and safety of antibiotic prophylaxis in reducing infectious puerperal morbidities in women undergoing operative vaginal deliveries including vacuum or forceps deliveries, or both. We searched Cochrane Pregnancy and Childbirth's Trials Register (12 July 2017), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (12 July 2017) and reference lists of retrieved studies. All randomised trials comparing any prophylactic antibiotic regimens with placebo or no treatment in women undergoing vacuum or forceps deliveries were eligible. Participants were all pregnant women without evidence of infections or other indications for antibiotics of any gestational age undergoing vacuum or forceps delivery for any indications. Interventions were any antibiotic prophylaxis (any dosage regimen, any route of administration or at any time during delivery or the puerperium) compared with either placebo or no treatment. Two review authors assessed trial eligibility and methodological quality. Two review authors extracted the data independently using prepared data extraction forms. Any discrepancies were resolved by discussion and a consensus reached through discussion with all review authors. We assessed methodological quality of the one included trial using the GRADE approach. One trial, involving 393 women undergoing either vacuum or forceps deliveries, was included. The trial compared the antibiotic intravenous cefotetan after cord clamping compared with no treatment. This trial reported only two out of the nine outcomes specified in this review. Seven women in the group

Fetal presentation and successful twin vaginal delivery.

PubMed

Easter, Sarah Rae; Lieberman, Ellice; Carusi, Daniela

2016-01-01

Despite the demonstrated safety of a trial of labor for pregnancies with a vertex-presenting twin and clinical guidelines in support of this plan, the rate of planned cesarean delivery for twin pregnancies remains high. This high rate, as well as variation in cesarean rates for twin pregnancies across providers, may be influenced strongly by concern about delivery of the second twin, particularly when it is in a nonvertex presentation. There are limited data in the literature that has examined the impact of the position of the nonpresenting twin on successful vaginal delivery or maternal/neonatal morbidity. We hypothesized that nonvertex presentation of the second twin would be associated with lower rates of successful vaginal birth for those patients attempting labor. This institutional review board-approved, retrospective cohort study of women who labored with twin pregnancies in a single urban hospital from 2007-2011. We included women with vertex-presenting first twins at >32 weeks gestation without a contraindication to labor and excluded those with uterine scar or lethal fetal anomaly. Vaginal delivery rates were evaluated according to vertex or nonvertex presentation of the second twin at admission and again at delivery. Maternal and neonatal morbidities were evaluated separately. Logistic regression was used to control for multiple confounders. Seven hundred sixteen patients met the inclusion criteria; 349 patients (49%) underwent a trial of labor. This included 73% (296/406) of eligible vertex/vertex twins and 17% (53/310) eligible vertex/nonvertex twins (P < .01). When compared with laboring patients with vertex/vertex-presenting twins, those with vertex/nonvertex twins were younger (median age, 32 vs 33 years; P = .05), were more often multiparous (60% vs 43%; P = .02), and were less likely to have hypertension (13% vs 27%; P = .03). Eighty-five percent of patients with nonvertex second twins at admission delivered vaginally, compared with 70% of

Filled Prescriptions for Opioids After Vaginal Delivery.

PubMed

Jarlenski, Marian; Bodnar, Lisa M; Kim, Joo Yeon; Donohue, Julie; Krans, Elizabeth E; Bogen, Debra L

2017-03-01

To estimate the prevalence of filled opioid prescriptions after vaginal delivery. We conducted a retrospective cohort study of 164,720 Medicaid-enrolled women in Pennsylvania who delivered a liveborn neonate vaginally from 2008 to 2013, excluding women who used opioids during pregnancy or who had an opioid use disorder. We assessed overall filled prescriptions as well as filled prescriptions in the presence or absence of the following pain-inducing conditions: bilateral tubal ligation, perineal laceration, or episiotomy. Outcomes included a binary measure of whether a woman had any opioid prescription fill 5 days or less after delivery and, among those women, a second opioid prescription fill 6-60 days after delivery. Among women with no coded pain-inducing conditions at delivery, we used multivariable logistic regression with standard errors clustered to account for within-hospital correlation to assess the association between patient characteristics and odds of a filled opioid prescription. Twelve percent of women (n=18,131) filled an outpatient opioid prescription 5 days or less after vaginal delivery; among those women, 14% (n=2,592, or 1.6% of the total) filled a second opioid prescription 6-60 days after delivery. Of the former, 5,110 (28.2%) had one or more pain-inducing conditions. Predictors of filled opioid prescriptions with no observed pain-inducing condition at delivery included tobacco use (adjusted odds ratio [OR] 1.3, 95% confidence interval [CI] 1.2-1.4) and a mental health condition (adjusted OR 1.3, 95% CI 1.2-1.4). Having a diagnosis of substance use disorder other than opioid use disorder was not associated with filling an opioid prescription 5 days or less after delivery, but was associated with having a second opioid prescription 6-60 days after delivery (adjusted OR 1.4, 95% CI 1.2-1.6). More than 1 in 10 Medicaid-enrolled women fill an outpatient opioid prescription after vaginal delivery. National opioid-prescribing recommendations for

Advanced topical drug delivery system for the management of vaginal candidiasis.

PubMed

Johal, Himmat Singh; Garg, Tarun; Rath, Goutam; Goyal, Amit Kumar

2016-01-01

Vaginal candidiasis or vulvovaginal candidiasis (VC) is a common mucosal infection of vagina, mainly caused by Candida species. The major symptoms of VC are dyspareunia, pruritis, itching, soreness, vagina as well as vulvar erythema and edema. Most common risk factors that lead to the imbalance in the vaginal micro biota are the use of antibiotics, pregnancy, diabetes mellitus, immuno suppression as in AIDS or HIV patients, frequent sexual intercourse, spermicide and intra-uterine devices and vaginal douching. Various anti-fungal drugs are available for effective treatment of VC. Different conventional vaginal formulations (creams, gels, suppositories, powder, ointment, etc.) for VC are available today but have limited efficacy because of lesser residence time on vaginal epithelium due to self-cleansing action of vagina. So to overcome this problem, an extended and intimate contact with vaginal mucosa is desired; which can be accomplished by utilizing mucoadhesive polymers. Mucoadhesive polymers have an excellent binding capacity to mucosal tissues for considerable period of time. This unique property of these polymers significantly enhances retention time of different formulations on mucosal tissues. Currently, various novel formulations such as liposomes, nano- and microparticles, micro-emulsions, bio-adhesive gel and tablets are used to control and treat VC. In this review, we focused on current status of vaginal candidiasis, conventional and nanotechnology inspired formulation approaches.

In vitro and ex vivo evaluation of polymeric nanoparticles for vaginal and rectal delivery of the anti-HIV drug dapivirine.

PubMed

das Neves, José; Araújo, Francisca; Andrade, Fernanda; Michiels, Johan; Ariën, Kevin K; Vanham, Guido; Amiji, Mansoor; Bahia, Maria Fernanda; Sarmento, Bruno

2013-07-01

Prevention strategies such as the development of microbicides are thought to be valuable in the fight against HIV/AIDS. Despite recent achievements, there is still a long road ahead in the field, particularly at the level of drug formulation. Drug nanocarriers based on polymers may be useful in enhancing local drug delivery while limiting systemic exposure. We prepared differently surface-engineered poly(ε-caprolactone) (PCL) nanoparticles (NPs) and tested their ability to modulate the permeability and retention of dapivirine in cell monolayers and pig vaginal and rectal mucosa. NPs coated with poly(ethylene oxide) (PEO) were shown able to reduce permeability across monolayers/tissues, while modification of nanosystems with cetyl trimethylammonium bromide (CTAB) enhanced transport. In the case of coating NPs with sodium lauryl sulfate (SLS), dapivirine permeability was unchanged. All NPs increased monolayer/tissue drug retention as compared to unformulated dapivirine. This fact was associated, at least partially, to the ability of NPs to be taken up by cells or penetrate mucosal tissue. Cell and tissue toxicity was also affected differently by NPs: PEO modification decreased the in vitro (but not ex vivo) toxicity of dapivirine, while higher toxicity was generally observed for NPs coated with SLS or CTAB. Overall, presented results support that PCL nanoparticles are capable of modulating drug permeability and retention in cell monolayers and mucosal tissues relevant for vaginal and rectal delivery of microbicides. In particular, PEO-modified dapivirine-loaded PCL NPs may be advantageous in increasing drug residence at epithelial cell lines/mucosal tissues, which may potentially increase the efficacy of microbicide drugs.

Antibiotic prophylaxis for operative vaginal delivery.

PubMed

Liabsuetrakul, Tippawan; Choobun, Thanapan; Peeyananjarassri, Krantarat; Islam, Q Monir

2014-10-13

Vacuum and forceps assisted vaginal deliveries are reported to increase the incidence of postpartum infections and maternal readmission to hospital compared to spontaneous vaginal delivery. Prophylactic antibiotics may be prescribed to prevent these infections. However, the benefit of antibiotic prophylaxis for operative vaginal deliveries is still unclear. To assess the effectiveness and safety of antibiotic prophylaxis in reducing infectious puerperal morbidities in women undergoing operative vaginal deliveries including vacuum or forceps deliveries, or both. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2014). All randomised trials comparing any prophylactic antibiotic regimens with placebo or no treatment in women undergoing vacuum or forceps deliveries were eligible. Participants were all pregnant women without evidence of infections or other indications for antibiotics of any gestational age undergoing vacuum or forceps delivery for any indications. Interventions were any antibiotic prophylaxis (any dosage regimen, any route of administration or at any time during delivery or the puerperium) compared with either placebo or no treatment. Two review authors assessed trial eligibility and methodological quality. Two review authors extracted the data independently using prepared data extraction forms. Any discrepancies were resolved by discussion and a consensus reached through discussion with all review authors. For this update, we assessed methodological quality of the one included trial using the standard Cochrane criteria and the GRADE approach. We calculated the risk ratio (RR) and mean difference (MD) using a fixed-effect model and all the review authors interpreted and discussed the results. One trial, involving 393 women undergoing either vacuum or forceps deliveries, was included. This trial identified only two out of the nine outcomes specified in this review. It reported seven women with endomyometritis in the

Antibiotic prophylaxis for operative vaginal delivery.

PubMed

Liabsuetrakul, T; Choobun, T; Peeyananjarassri, K; Islam, M

2004-01-01

Vacuum and forceps assisted vaginal deliveries are reported to increase the incidence of postpartum infections and maternal readmission to hospital compared to spontaneous vaginal delivery. Prophylactic antibiotics are prescribed to prevent these infections. However, the benefit of antibiotic prophylaxis for operative vaginal deliveries is still unclear. To assess the effectiveness and safety of antibiotic prophylaxis in reducing infectious puerperal morbidities in women undergoing operative vaginal deliveries including vacuum and/or forceps deliveries. We searched the Cochrane Pregnancy and Childbirth Group trials register (November 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2003) and MEDLINE (1966 to November 2003). All randomised trials comparing any prophylactic antibiotic regimens with placebo or no treatment in women undergoing vacuum or forceps deliveries were eligible. Participants were all pregnant women without evidence of infections or other indications for antibiotics of any gestational age undergoing vacuum or forceps delivery for any indications. Interventions were any antibiotic prophylaxis (any dosage regimen, any route of administration or at any time during delivery or the puerperium) compared with either placebo or no treatment. Four reviewers assessed trial eligibility and methodological quality. Two reviewers extracted the data independently using prepared data extraction forms. Any discrepancies were resolved by discussion and a consensus reached through discussion with all reviewers. We assessed methodological quality of the included trial using the standard Cochrane criteria and the CONSORT statement of randomised controlled trials. We calculated the relative risks using a fixed effect model and all the reviewers interpreted and discussed the results. One trial, involving 393 women undergoing either vacuum or forceps deliveries, was included. This trial identified only two out of the nine

Dinoprostone vaginal insert versus intravenous oxytocin to reduce postpartum blood loss following vaginal or cesarean delivery.

PubMed

Ozalp, E; Tanir, H M; Sener, T

2010-01-01

To compare the impact of a dinoprostone vaginal insert and intravenous oxytocin in reducing blood loss of women undergoing vaginal or cesarean delivery. This study was conducted among term singleton pregnancies delivered vaginally or by elective cesarean section. In the vaginally delivered cases, active management of the third stage of labor was conducted. During cesarean delivery, 20 IU of intravenous oxytocin was administered. Women, who either delivered via the vaginal or abdominal route, were then randomly allocated to receive 10 mg vaginal dinoprostone insert for 12 hours (group I, n: 100) or intravenous oxytocin (group II, n: 100), respectively. Mean blood loss and need for additional uterotonics and postpartum hemoglobin and hematocrit levels at 24 and 36 hours after delivery did not differ between the two groups. Women allocated to the dinoprostone vaginal insert arm experienced more nausea and vomiting. Dinoprostone vaginal insert was as effective as intravenous oxytocin in the prevention of postpartum blood loss.

Successful vaginal delivery at term after vaginal reconstruction with labium minus flaps in a patient with vaginal atresia: A rare case report.

PubMed

Liu, Yu; Wang, Yi-Feng

2017-07-01

We report a case of successful vaginal delivery after vaginal reconstruction with labium minus flaps in a 23-year-old patient with congenital vaginal atresia. The patient primarily presented with amenorrhea and cyclic abdominal pain; transabdominal ultrasonography revealed an enlarged uterus due to hematometra and absence of the lower segment of the vagina. Eight years ago, she had undergone an unsuccessful attempt at canalization at a local hospital. Upon referral to our hospital, she underwent vaginal reconstruction with labium minus flaps. Four months after this procedure, she became pregnant and, subsequently, successfully and safely vaginally delivered a healthy female baby weighing 3250 g at 38 +1 weeks' gestation. The delivery did not involve perineal laceration by lateral episiotomy. To the best of our knowledge, this is the first reported case of successful vaginal delivery at term after vaginal reconstruction with labium minus flaps in a patient with vaginal atresia. © 2017 Japan Society of Obstetrics and Gynecology.

An Audit of Singleton Breech Deliveries in a Hospital with a High Rate of Vaginal Delivery

PubMed Central

Nordin, Noraihan Mohd.

2007-01-01

The term breech trial (TBT) has brought about radical changes but it is debatable whether it provides unequivocal evidence regarding the practice of breech deliveries. There is a need to publish the data of a study that was performed before the era of the TBT in a hospital where there was a high rate of breech vaginal delivery. The objectives were to ascertain the incidence, mode of delivery and fetal outcome in singleton breech deliveries. The study design was a retrospective cohort study where 165 consecutive breech and 165 controls (cephalic) were included. Statistical analysis, used were Chi squared and Fischer’s exact test. P<0.05 is taken as the level of significance. The incidence of breech deliveries was found to be 3% and has remained fairly constant but the rate of breech vaginal delivery has fallen and the CS rates have increased. Even though more breech compared to controls were significantly sectioned, majority of the breeches {n=137 (83%)} were planned for vaginal delivery and in these patients two-thirds attained vaginal delivery. There was 1 fetal death in the CS group compared to 12 deaths in the vaginally delivered breech. However, most death in the breech delivered vaginally are unavoidable. In conclusion, there is a high rate of breech vaginal delivery in this series of patients and most perinatal deaths were not related to the mode of delivery. PMID:22593649

Vernix caseosa peritonitis after vaginal delivery.

PubMed

Sadath, Shameema A; Abo Diba, Fathiya I; Nayak, Surendra; Shamali, Iman Al; Diejomaoh, Michael F

2013-01-01

Vernix caseosa peritonitis (VCP) is a very unusual complication caused by inflammatory response to amniotic fluid spilled into the maternal peritoneal cavity. Twenty-seven cases have been reported, and all occurred after cesarean section. We present a case of VCP following vaginal delivery; this may be the first case reported after vaginal delivery. Mrs. A, 28 years old, gravida 3, para 2, with one previous cesarean section, was admitted at 41 weeks gestation in active labor. Vacuum extraction was performed to deliver a healthy male baby, 4.410 kg, Apgar scores 7, 8. She developed fever, acute abdominal pain, and distension about 3 hours after delivery. A diagnosis of acute abdomen was made. Laparotomy was performed and it revealed neither uterine scar rupture nor other surgical emergencies, but 500 mL of turbid fluid and some cheesy material on the serosal surface of all viscera. Biopsies were taken. She had a course of antibiotics and her recovery was complete. Histology of the peritoneal fluid and tissue biopsy resulted in a diagnosis of VCP. Clinical diagnosis of peritonitis due to vernix caseosa should be considered in patients presenting postpartum with an acute abdomen after vaginal delivery.

Reducing high-order perineal laceration during operative vaginal delivery.

PubMed

Hirsch, Emmet; Haney, Elaine I; Gordon, Trent E J; Silver, Richard K

2008-06-01

This study was undertaken to assess the impact of a focused intervention on reducing high-order (third and fourth degree) perineal lacerations during operative vaginal delivery. The following recommendations for clinical management were promulgated by departmental lectures, distribution of pertinent articles and manuals, training of physicians, and prominent display of an instructional poster: (1) increased utilization of vacuum extraction over forceps delivery; (2) conversion of occiput posterior to anterior positions before delivery; (3) performance of mediolateral episiotomy if episiotomy was deemed necessary; (4) flexion of the fetal head and maintenance of axis traction; (5) early disarticulation of forceps; and (6) reduced maternal effort at expulsion. Peer comparison was encouraged by provision of individual and departmental statistics. Clinical data were extracted from the labor and delivery database and the medical record. One hundred fifteen operative vaginal deliveries occurred in the 3 quarters preceding the intervention, compared with 100 afterward (P = .36). High-order laceration with operative vaginal delivery declined from 41% to 26% (P = .02), coincident with increased use of vacuum (16% vs 29% of operative vaginal deliveries, P = .02); fewer high-order lacerations after episiotomy (63% vs 22%, P = .003); a nonsignificant reduction in performance of episiotomy (30% vs 23%, P = .22); and a nonsignificant increase in mediolateral episiotomy (14% vs 30% of episiotomies, P = .19). Introduction of formal practice recommendations and performance review was associated with diminished high-order perineal injury with operative vaginal delivery.

Chitosan/alginate complexes for vaginal delivery of chlorhexidine digluconate.

PubMed

Abruzzo, A; Bigucci, F; Cerchiara, T; Saladini, B; Gallucci, M C; Cruciani, F; Vitali, B; Luppi, B

2013-01-16

Chitosan/alginate complexes were prepared at different polycation/polyanion molar ratios and freeze-dried vaginal inserts were obtained for chlorhexidine digluconate local delivery in genital infections. Complex yield, FT-IR spectra, and TGA thermograms were studied to confirm the interaction between the two polyions. The influence of different complexes on physical handling, morphology, and drug distribution in the samples were evaluated by friability test, scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDS), respectively. In vitro water-uptake, mucoadhesion and release tests were performed as well as microbiological tests toward pathogenic vaginal microorganisms. The results showed that the selection of suitable chitosan/alginate molar ratio and drug loading allowed modulate insert ability to hydrate, adhere to the mucosa, and release chlorhexidine digluconate. The insert containing an excess of alginate was found to be the best performing formulation and showed good antimicrobial activity toward the pathogens Candida albicans and Escherichia coli. Copyright © 2012 Elsevier Ltd. All rights reserved.

Predictors of shoulder dystocia at the time of operative vaginal delivery.

PubMed

Palatnik, Anna; Grobman, William A; Hellendag, Madeline G; Janetos, Timothy M; Gossett, Dana R; Miller, Emily S

2016-11-01

It remains uncertain whether clinical factors known prior to delivery can predict which women are more likely to experience shoulder dystocia in the setting of operative vaginal delivery. We sought to identify whether shoulder dystocia can be accurately predicted among women undergoing an operative vaginal delivery. This was a case-control study of women undergoing a low or outlet operative vaginal delivery from 2005 through 2014 in a single tertiary care center. Cases were defined as women who experienced a shoulder dystocia at the time of operative vaginal delivery. Controls consisted of women without a shoulder dystocia at the time of operative vaginal delivery. Variables previously identified to be associated with shoulder dystocia that could be known prior to delivery were abstracted from the medical records. Bivariable analyses and multivariable logistic regression were used to identify factors independently associated with shoulder dystocia. A receiver operating characteristic curve was created to evaluate the predictive value of the model for shoulder dystocia. Of the 4080 women who met inclusion criteria, shoulder dystocia occurred in 162 (4.0%) women. In bivariable analysis, maternal age, parity, body mass index, diabetes, chorioamnionitis, arrest disorder as an indication for an operative vaginal delivery, vacuum use, and estimated fetal weight >4 kg were significantly associated with shoulder dystocia. In multivariable analysis, parity, diabetes, chorioamnionitis, arrest disorder as an indication for operative vaginal delivery, vacuum use, and estimated fetal weight >4 kg remained independently associated with shoulder dystocia. The area under the curve for the generated receiver operating characteristic curve was 0.73 (95% confidence interval, 0.69-0.77), demonstrating only a modest ability to predict shoulder dystocia before performing an operative vaginal delivery. While risk factors for shoulder dystocia at the time of operative vaginal delivery

Development and in vivo safety assessment of tenofovir-loaded nanoparticles-in-film as a novel vaginal microbicide delivery system.

PubMed

Machado, Alexandra; Cunha-Reis, Cassilda; Araújo, Francisca; Nunes, Rute; Seabra, Vítor; Ferreira, Domingos; das Neves, José; Sarmento, Bruno

2016-10-15

Topical pre-exposure prophylaxis (PrEP) with antiretroviral drugs holds promise in preventing vaginal transmission of HIV. However, significant biomedical and social issues found in multiple past clinical trials still need to be addressed in order to optimize protection and users' adherence. One approach may be the development of improved microbicide products. A novel delivery platform comprising drug-loaded nanoparticles (NPs) incorporated into a thin polymeric film base (NPs-in-film) was developed in order to allow the vaginal administration of the microbicide drug candidate tenofovir. The system was optimized for relevant physicochemical features and characterized for biological properties, namely cytotoxicity and safety in a mouse model. Tenofovir-loaded poly(lactic-co-glycolic acid) (PLGA)/stearylamine (SA) composite NPs with mean diameter of 127nm were obtained with drug association efficiency above 50%, and further incorporated into an approximately 115μm thick, hydroxypropyl methylcellulose/poly(vinyl alcohol)-based film. The system was shown to possess suitable mechanical properties for vaginal administration and to quickly disintegrate in approximately 9min upon contact with a simulated vaginal fluid (SVF). The original osmolarity and pH of SVF was not affected by the film. Tenofovir was also released in a biphasic fashion (around 30% of the drug in 15min, followed by sustained release up to 24h). The incorporation of NPs further improved the adhesive potential of the film to ex vivo pig vaginal mucosa. Cytotoxicity of NPs and film was significantly increased by the incorporation of SA, but remained at levels considered tolerable for vaginal delivery of tenofovir. Moreover, histological analysis of genital tissues and cytokine/chemokine levels in vaginal lavages upon 14days of daily vaginal administration to mice confirmed that tenofovir-loaded NPs-in-film was safe and did not induce any apparent histological changes or pro-inflammatory response. Overall

Thromboprophylaxis after vaginal delivery: a district general hospital experience.

PubMed

Potdar, N; Jabbar, B; Burrell, S J

2006-01-01

The Confidential Enquiries into Maternal Deaths (RCOG 2001) recommends risk assessment and appropriate thromboprophylaxis after vaginal delivery. This study examines the risk group and the need for thromboprophylaxis after vaginal delivery in our local population and the cost implications for the same. It is a retrospective study of women who delivered in the month of November 2003. There were 307 deliveries, of these 251 (81.7%) were vaginal deliveries. Confidential Enquiries into Maternal Deaths (CEMD) risk classification was possible for 243 women. A total of 170 women were low risk, 66 (27.16%) moderate risk and 7 (2.88%) high risk. The costs of thromboprophylaxis for the year in our unit were calculated as pound7,339.71 for unfractionated heparin (UFH) 5,000 IU twice daily and pound7,098.27 for 40 mg enoxaparin once daily. A total of 30% of our District General Hospital population were classified as moderate or high risk for thromboprophylaxis after vaginal delivery. It is less expensive to use enoxaparin compared with unfractionated heparin for thromboprophylaxis.

Prenatal attitudes toward vaginal delivery and actual delivery mode: Variation by race/ethnicity and socioeconomic status.

PubMed

Attanasio, Laura B; Hardeman, Rachel R; Kozhimannil, Katy B; Kjerulff, Kristen H

2017-12-01

Researchers documenting persistent racial/ethnic and socioeconomic status disparities in chances of cesarean delivery have speculated that women's birth attitudes and preferences may partially explain these differences, but no studies have directly tested this hypothesis. We examined whether women's prenatal attitudes toward vaginal delivery differed by race/ethnicity or socioeconomic status, and whether attitudes were differently related to delivery mode depending on race/ethnicity or socioeconomic status. Data were from the First Baby Study, a cohort of 3006 women who gave birth to a first baby in Pennsylvania between 2009 and 2011. We used regression models to examine (1) predictors of prenatal attitudes toward vaginal delivery, and (2) the association between prenatal attitudes and actual delivery mode. To assess moderation, we estimated models adding interaction terms. Prenatal attitudes toward vaginal delivery were not associated with race/ethnicity or socioeconomic status. Positive attitudes toward vaginal delivery were associated with lower odds of cesarean delivery (AOR=0.60, P < .001). However, vaginal delivery attitudes were only related to delivery mode among women who were white, highly educated, and privately insured. There are racial/ethnic differences in chances of cesarean delivery, and these differences are not explained by birth attitudes. Furthermore, our findings suggest that white and high-socioeconomic status women may be more able to realize their preferences in childbirth. © 2017 Wiley Periodicals, Inc.

Simulation training and resident performance of singleton vaginal breech delivery.

PubMed

Deering, Shad; Brown, Jill; Hodor, Jonathon; Satin, Andrew J

2006-01-01

To determine whether simulation training improves resident competency in the management of a simulated vaginal breech delivery. Without advance notice or training, residents from 2 obstetrics and gynecology residency programs participated in a standardized simulation scenario of management of an imminent term vaginal breech delivery. The scenario used an obstetric birth simulator and human actors, with the encounters digitally recorded. Residents then received a training session with the simulator on the proper techniques for vaginal breech delivery. Two weeks later they were retested using a similar simulation scenario. A physician, blinded to training status, graded the residents' performance using a standardized evaluation sheet. Statistical analysis included the Wilcoxon signed rank test, McNemar chi2, regression analysis, and paired t test as appropriate with a P value of less than .05 considered significant. Twenty residents from 2 institutions completed all parts of the study protocol. Trained residents had significantly higher scores in 8 of 12 critical delivery components (P < .05). Overall performance of the delivery and safety in performing the delivery also improved significantly (P = .001 for both). Simulation training improved resident performance in the management of a simulated vaginal breech delivery. Performance of a term breech vaginal delivery is well suited for simulation training, because it is uncommon and inevitable, and improper technique may result in significant injury. II-2.

Reoccurrence of retained placenta at vaginal delivery: an observational study.

PubMed

Nikolajsen, Sys; Løkkegaard, Ellen Christine Leth; Bergholt, Thomas

2013-04-01

To estimate the prevalence and validate the diagnosis of retained placenta in nulliparous women and the risk of reoccurrence at subsequent vaginal delivery. Nested cohort study. Department of Gynecology and Obstetrics, university-affiliated teaching hospital. 10 334 nulliparous singleton pregnancies who delivered vaginally at the hospital during 2000-2009. Data from a computerized database information system were used to identify 287 women who had an ICD-10 diagnosis of retained placenta and 572 randomly selected controls matched by the date of first delivery. At chart review the diagnosis was confirmed by: (1) excessive bleeding <30 minutes after delivery without placental separation, (2) placenta not separated 30 minutes after delivery or (3) confirmation of retained placental tissue >2 hours postpartum. Confirmation of the diagnosis and prevalence of retained placenta. Risk of reoccurrence in a subsequent vaginal delivery. The prevalence of retained placenta increased from 2.8 to 7.0% after confirmation according to the set criteria. Of the selected women, 48.4% had a subsequent vaginal delivery. Of these women, 25.3% (23/91) with a previous retained placenta and 5.3% (11/206) without previously retained placenta, experienced retained placenta in subsequent delivery. This corresponds to an adjusted odds ratio of 5.5 (95% confidence interval 2.6-12.7) in the multivariate analysis for recurrence of retained placenta in a subsequent vaginal delivery. The use of the ICD-10 diagnosis of retained placenta underestimated the prevalence. The risk of reoccurrence of retained placenta is significantly increased in a subsequent vaginal delivery. © 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica © 2012 Nordic Federation of Societies of Obstetrics and Gynecology.

Drivers of Vaginal Drug Delivery System Acceptability from Internet-Based Conjoint Analysis.

PubMed

Primrose, Rachel J; Zaveri, Toral; Bakke, Alyssa J; Ziegler, Gregory R; Moskowitz, Howard R; Hayes, John E

2016-01-01

Vaginal microbicides potentially empower women to protect themselves from HIV and other sexually transmitted infections (STIs), especially when culture, religion, or social status may prevent them from negotiating condom use. The open literature contains minimal information on factors that drive user acceptability of women's health products or vaginal drug delivery systems. By understanding what women find to be most important with regard to sensory properties and product functionality, developers can iteratively formulate a more desirable product. Conjoint analysis is a technique widely used in market research to determine what combination of elements influence a consumer's willingness to try or use a product. We applied conjoint analysis here to better understand what sexually-active woman want in a microbicide, toward our goal of formulating a product that is highly acceptable to women. Both sensory and non-sensory attributes were tested, including shape, color, wait time, partner awareness, messiness/leakage, duration of protection, and functionality. Heterosexually active women between 18 and 35 years of age in the United States (n = 302) completed an anonymous online conjoint survey using IdeaMap software. Attributes (product elements) were systematically presented in various combinations; women rated these combinations of a 9-point willingness-to-try scale. By coupling systematic combinations and regression modeling, we can estimate the unique appeal of each element. In this population, a multifunctional product (i.e., broad spectrum STI protection, coupled with conception) is far more desirable than a microbicide targeted solely for HIV protection; we also found partner awareness and leakage are potentially strong barriers to use.

Drivers of Vaginal Drug Delivery System Acceptability from Internet-Based Conjoint Analysis

PubMed Central

Primrose, Rachel J.; Zaveri, Toral; Bakke, Alyssa J.; Ziegler, Gregory R.; Moskowitz, Howard R.; Hayes, John E.

2016-01-01

Vaginal microbicides potentially empower women to protect themselves from HIV and other sexually transmitted infections (STIs), especially when culture, religion, or social status may prevent them from negotiating condom use. The open literature contains minimal information on factors that drive user acceptability of women’s health products or vaginal drug delivery systems. By understanding what women find to be most important with regard to sensory properties and product functionality, developers can iteratively formulate a more desirable product. Conjoint analysis is a technique widely used in market research to determine what combination of elements influence a consumer’s willingness to try or use a product. We applied conjoint analysis here to better understand what sexually-active woman want in a microbicide, toward our goal of formulating a product that is highly acceptable to women. Both sensory and non-sensory attributes were tested, including shape, color, wait time, partner awareness, messiness/leakage, duration of protection, and functionality. Heterosexually active women between 18 and 35 years of age in the United States (n = 302) completed an anonymous online conjoint survey using IdeaMap software. Attributes (product elements) were systematically presented in various combinations; women rated these combinations of a 9-point willingness-to-try scale. By coupling systematic combinations and regression modeling, we can estimate the unique appeal of each element. In this population, a multifunctional product (i.e., broad spectrum STI protection, coupled with conception) is far more desirable than a microbicide targeted solely for HIV protection; we also found partner awareness and leakage are potentially strong barriers to use. PMID:26999009

Characterisation of the vaginal Lactobacillus microbiota associated with preterm delivery.

PubMed

Petricevic, Ljubomir; Domig, Konrad J; Nierscher, Franz Josef; Sandhofer, Michael J; Fidesser, Maria; Krondorfer, Iris; Husslein, Peter; Kneifel, Wolfgang; Kiss, Herbert

2014-05-30

The presence of an abnormal vaginal microflora in early pregnancy is a risk factor for preterm delivery. There is no investigation on vaginal flora dominated by lactic acid bacteria and possible association with preterm delivery. We assessed the dominant vaginal Lactobacillus species in healthy pregnant women in early pregnancy in relation to pregnancy outcome. We observed 111 low risk pregnant women with a normal vaginal microflora 11 + 0 to 14 + 0 weeks of pregnancy without subjective complaints. Vaginal smears were taken for the identification of lactobacilli using denaturing gradient gel electrophoresis (DGGE). Pregnancy outcome was recorded as term or preterm delivery (limit 36 + 6 weeks of gestation). The diversity of Lactobacillus species in term vs. preterm was the main outcome measure. L. iners alone was detected in 11 from 13 (85%) women who delivered preterm. By contrast, L. iners alone was detected in only 16 from 98 (16%) women who delivered at term (p < 0.001). Fifty six percent women that delivered at term and 8% women that delivered preterm had two or more vaginal Lactobacillus spp. at the same time. This study suggests that dominating L. iners alone detected in vaginal smears of healthy women in early pregnancy might be associated with preterm delivery.

Vaginal distribution and retention of a multiparticulate drug delivery system, assessed by gamma scintigraphy and magnetic resonance imaging.

PubMed

Mehta, Samata; Verstraelen, Hans; Peremans, Kathelijne; Villeirs, Geert; Vermeire, Simon; De Vos, Filip; Mehuys, Els; Remon, Jean Paul; Vervaet, Chris

2012-04-15

promising novel vaginal drug delivery system, resulting in complete coverage of the vaginal mucosa and long retention time. Copyright © 2012 Elsevier B.V. All rights reserved.

Mucoadhesive drug delivery systems

PubMed Central

Shaikh, Rahamatullah; Raj Singh, Thakur Raghu; Garland, Martin James; Woolfson, A David; Donnelly, Ryan F.

2011-01-01

Mucoadhesion is commonly defined as the adhesion between two materials, at least one of which is a mucosal surface. Over the past few decades, mucosal drug delivery has received a great deal of attention. Mucoadhesive dosage forms may be designed to enable prolonged retention at the site of application, providing a controlled rate of drug release for improved therapeutic outcome. Application of dosage forms to mucosal surfaces may be of benefit to drug molecules not amenable to the oral route, such as those that undergo acid degradation or extensive first-pass metabolism. The mucoadhesive ability of a dosage form is dependent upon a variety of factors, including the nature of the mucosal tissue and the physicochemical properties of the polymeric formulation. This review article aims to provide an overview of the various aspects of mucoadhesion, mucoadhesive materials, factors affecting mucoadhesion, evaluating methods, and finally various mucoadhesive drug delivery systems (buccal, nasal, ocular, gastro, vaginal, and rectal). PMID:21430958

The immediate effect of vaginal and caesarean delivery on anal sphincter measurements.

PubMed

Karcaaltincaba, Deniz; Erkaya, Salim; Isik, Hatice; Haberal, Ali

2016-08-01

This study evaluated the effects of vaginal and caesarean delivery on internal and external anal sphincter muscle thickness using translabial ultrasonography (TL-US). This prospective cohort study enrolled nulliparous women who either had vaginal or caesarean deliveries. The thickness of the hypoechoic internal anal sphincter (IAS) and hyperechoic external anal sphincter (EAS) at the 12, 3, 6, and 9 o'clock positions at the distal level were measured before delivery and within 24-48 h after delivery. A total 105 consecutive women were enrolled in the study: 60 in the vaginal delivery group and 45 in the caesarean delivery group. The IAS muscle thickness at the 12 o'clock position in the vaginal delivery group was significantly thicker before compared with after delivery (mean ± SD: 2.31 ± 0.74 mm versus 1.81 ± 0.64 mm, respectively). The EAS muscle thickness at the 12 o'clock position in the vaginal delivery group was significantly thicker before compared with after delivery (mean ± SD: 2.42 ± 0.64 mm versus 1.97 ± 0.85, respectively). There was significant muscle thinning of both the IAS and EAS at the 12 o'clock position after vaginal delivery, but not after caesarean delivery. © The Author(s) 2016.

[Progress in research of relationship between vaginal Lactobacillus and preterm delivery].

PubMed

He, Y N; Xiong, H Y; Zheng, Y J

2017-03-10

The vaginal flora in most healthy women is dominated by Lactobacillus species. The absence of Lactobacillus species in vaginal flora might lead to a series of symptoms, especially in pregnant women causing adverse pregnancy outcomes, such as preterm delivery. This review focuses on the progress in the research of the relationship between vaginal Lactobacillus and preterm delivery, providing reference for the reduction of the incidence of preterm delivery.

Designing and developing suppository formulations for anti-HIV drug delivery.

PubMed

Ham, Anthony S; Buckheit, Robert W

2017-08-01

Despite a long history of use for rectal and vaginal drug delivery, the current worldwide market for suppositories is limited primarily due to a lack of user acceptability. Therefore, virtually no rational pharmaceutical development of antiviral suppositories has been performed. However, suppositories offer several advantages over other antiviral dosage forms. Current suppository designs have integrated active pharmaceutical ingredients into existing formulation designs without optimization. As such, emerging suppository development has been focused on improving upon the existing classical design to enhance drug delivery and is poised to open suppository drug delivery to a broader range of drugs, including antiretroviral products. Thus, with continuing research into rational suppository design and development, there is significant potential for antiretroviral suppository drug delivery.

Osmolarity as a contributing factor in topical drug delivery

NASA Astrophysics Data System (ADS)

Funke, Claire; Szeri, Andrew J.

2017-11-01

Gels and dissolvable solids are drug delivery platforms being evaluated for application of active pharmaceutical ingredients, termed microbicides, which act topically against infection by sexually transmitted HIV. In previous work, we have investigated how dilution by naturally produced fluid from the vaginal mucosa affects drug transport into the vaginal wall. We expand on this work by no longer assuming a constant flux and instead developing a relation for fluid transport based on osmolarity - thus allowing fluid to pass both into and out of epithelial cells. This relation shows that varying the osmolarity of the applied solution can have a significant effect on the amount of drug delivered to its target while holding the applied amount constant. This effect is modulated by a dimensionless group that relates the rates of solute and solvent transport. Ultimately, our goal is to develop a tool to understand better how to manipulate solution osmolarity in order to improve drug delivery within safety parameters for mucosal tissue.

Spray-Dried Thiolated Chitosan-Coated Sodium Alginate Multilayer Microparticles for Vaginal HIV Microbicide Delivery.

PubMed

Meng, Jianing; Agrahari, Vivek; Ezoulin, Miezan J; Purohit, Sudhaunshu S; Zhang, Tao; Molteni, Agostino; Dim, Daniel; Oyler, Nathan A; Youan, Bi-Botti C

2017-05-01

It is hypothesized that novel thiolated chitosan-coated multilayer microparticles (MPs) with enhanced drug loading are more mucoadhesive than uncoated MPs and safe in vivo for vaginal delivery of topical anti-HIV microbicide. Formulation optimization is achieved through a custom experimental design and the alginate (AG) MPs cores are prepared using the spray drying method. The optimal MPs are then coated with the thiolated chitosan (TCS) using a layer-by-layer method. The morphological analysis, in situ drug payload, in vitro drug release profile, and mucoadhesion potential of the MPs are carried out using scanning electron microscopy, solid-state 31 P NMR spectroscopy, UV spectroscopy, fluorescence imaging and periodic acid Schiff method, respectively. The cytotoxicity and preclinical safety of MPs are assessed on human vaginal (VK2/E6E7) and endocervical (End1/E6E7) epithelial cell lines and in female C57BL/6 mice, respectively. The results show that the MPs are successfully formulated with an average diameter ranging from 2 to 3 μm with a drug loading of 7-12% w/w. The drug release profile of these MPs primarily follows the Baker-Lonsdale and Korsmeyer-Peppas models. The MPs exhibit high mucoadhesion (20-50 folds) compared to native AGMPs. The multilayer MPs are noncytotoxic. Histological and immunochemical analysis of the mice genital tract shows neither signs of damage nor inflammatory cell infiltrate. These data highlight the potential use of TCS-coated AG-based multilayer MPs templates for the topical vaginal delivery of anti-HIV/AIDS microbicides.

A randomized trial of planned cesarean or vaginal delivery for twin pregnancy.

PubMed

Barrett, Jon F R; Hannah, Mary E; Hutton, Eileen K; Willan, Andrew R; Allen, Alexander C; Armson, B Anthony; Gafni, Amiram; Joseph, K S; Mason, Dalah; Ohlsson, Arne; Ross, Susan; Sanchez, J Johanna; Asztalos, Elizabeth V

2013-10-03

Twin birth is associated with a higher risk of adverse perinatal outcomes than singleton birth. It is unclear whether planned cesarean section results in a lower risk of adverse outcomes than planned vaginal delivery in twin pregnancy. We randomly assigned women between 32 weeks 0 days and 38 weeks 6 days of gestation with twin pregnancy and with the first twin in the cephalic presentation to planned cesarean section or planned vaginal delivery with cesarean only if indicated. Elective delivery was planned between 37 weeks 5 days and 38 weeks 6 days of gestation. The primary outcome was a composite of fetal or neonatal death or serious neonatal morbidity, with the fetus or infant as the unit of analysis for the statistical comparison. A total of 1398 women (2795 fetuses) were randomly assigned to planned cesarean delivery and 1406 women (2812 fetuses) to planned vaginal delivery. The rate of cesarean delivery was 90.7% in the planned-cesarean-delivery group and 43.8% in the planned-vaginal-delivery group. Women in the planned-cesarean-delivery group delivered earlier than did those in the planned-vaginal-delivery group (mean number of days from randomization to delivery, 12.4 vs. 13.3; P=0.04). There was no significant difference in the composite primary outcome between the planned-cesarean-delivery group and the planned-vaginal-delivery group (2.2% and 1.9%, respectively; odds ratio with planned cesarean delivery, 1.16; 95% confidence interval, 0.77 to 1.74; P=0.49). In twin pregnancy between 32 weeks 0 days and 38 weeks 6 days of gestation, with the first twin in the cephalic presentation, planned cesarean delivery did not significantly decrease or increase the risk of fetal or neonatal death or serious neonatal morbidity, as compared with planned vaginal delivery. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00187369; Current Controlled Trials number, ISRCTN74420086.).

Implementation of a protocol to reduce occurrence of retained sponges after vaginal delivery.

PubMed

Lutgendorf, Monica A; Schindler, Lynnett L; Hill, James B; Magann, Everett F; O'Boyle, John D

2011-06-01

Retained sponges (gossypiboma) following vaginal delivery are an uncommon occurrence. Although significant morbidity from such an event is unlikely, there are many reported adverse effects, including symptoms of malodorous discharge, loss of confidence in providers and the medical system, and legal claims. To report a protocol intended to reduce the occurrence of retained sponges following vaginal delivery. After identification of limitations with existing delivery room protocols, we developed a sponge count protocol to reduce occurrence of retained vaginal sponges. We report our experience at Naval Medical Center Portsmouth, a large tertiary care military treatment facility with our efforts to implement a sponge count protocol to reduce retained sponges following vaginal delivery. With appropriate pre-implementation training, protocols which incorporate post-delivery vaginal sweep and sponge counts are well accepted by the health care team and can be incorporated into the delivery room routine.

Risk factors for cesarean section and instrumental vaginal delivery after successful external cephalic version.

PubMed

de Hundt, Marcella; Vlemmix, Floortje; Bais, Joke M J; de Groot, Christianne J; Mol, Ben Willem; Kok, Marjolein

2016-01-01

Aim of this article is to examine if we could identify factors that predict cesarean section and instrumental vaginal delivery in women who had a successful external cephalic version. We used data from a previous randomized trial among 25 hospitals and their referring midwife practices in the Netherlands. With the data of this trial, we performed a cohort study among women attempting vaginal delivery after successful ECV. We evaluated whether maternal age, gestational age, parity, time interval between ECV and delivery, birth weight, neonatal gender, and induction of labor were predictive for a vaginal delivery on one hand or a CS or instrumental vaginal delivery on the other hand. Unadjusted and adjusted odds ratios were calculated with univariate and multivariate logistic regression analysis. Among 301 women who attempted vaginal delivery after a successful external cephalic version attempt, the cesarean section rate was 13% and the instrumental vaginal delivery rate 6%, resulting in a combined instrumental delivery rate of 19%. Nulliparity increased the risk of cesarean section (OR 2.7 (95% CI 1.2-6.1)) and instrumental delivery (OR 4.2 (95% CI 2.1-8.6)). Maternal age, gestational age at delivery, time interval between external cephalic version and delivery, birth weight and neonatal gender did not contribute to the prediction of failed spontaneous vaginal delivery. In our cohort of 301 women with a successful external cephalic version, nulliparity was the only one of seven factors that predicted the risk for cesarean section and instrumental vaginal delivery.

Development and characterization of polymer-coated liposomes for vaginal delivery of sildenafil citrate.

PubMed

Refai, Hanan; Hassan, Doaa; Abdelmonem, Rehab

2017-11-01

Vaginal administration of sildenafil citrate has shown recently to develop efficiently the uterine lining with subsequent successful embryo implantation following in vitro fertilization. The aim of the present study was to develop sildenafil-loaded liposomes coated with bioadhesive polymers for enhanced vaginal retention and improved drug permeation. Three liposomal formulae were prepared by thin-film method using different phospholipid:cholesterol ratios. The optimal liposomal formulation was coated with bioadhesive polymers (chitosan and HPMC). A marked increase in liposomal size and zeta potential was observed for all coated liposomal formulations. HPMC-coated liposomes showed the greater bioadhesion and higher entrapment efficiency than chitosan-coated formulae. The in vitro release studies showed prolonged release of sildenafil from coated liposomes as compared to uncoated liposomes and sildenafil solution. Ex vivo permeation study revealed the enhanced permeation of coated relative to uncoated liposomes. Chitosan-coated formula demonstrated highest drug permeation and was thus selected for further investigations. Transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR) confirmed the successful coating of the liposomes by chitosan. Histopathological in vivo testing proved the efficacy of chitosan-coated liposomes to improve blood flow to the vaginal endometrium and to increase endometrial thickness. Chitosan-coated liposomes can be considered as potential novel drug delivery system intended for the vaginal administration of sildenafil, which would prolong system's retention at the vaginal site and enhance the permeation of sildenafil to uterine blood circulation.

In vitro evaluation of mucoadhesive vaginal tablets of antifungal drugs prepared with thiolated polymer and development of a new dissolution technique for vaginal formulations.

PubMed

Baloglu, Esra; Ay Senyıgıt, Zeynep; Karavana, Sinem Yaprak; Vetter, Anja; Metın, Dilek Yesim; Hilmioglu Polat, Suleyha; Guneri, Tamer; Bernkop-Schnurch, Andreas

2011-01-01

The main objective of this work was to develop antifungal matrix tablet for vaginal applications using mucoadhesive thiolated polymer. Econazole nitrate (EN) and miconazole nitrate (MN) were used as antifungal drugs to prepare the vaginal tablet formulations. Thiolated poly(acrylic acid)-cysteine (PAA-Cys) conjugate was synthesized by the covalent attachment of L-cysteine to PAA with the formation of amide bonds between the primary amino group of L-cysteine and the carboxylic acid group of the polymer. Vaginal mucoadhesive matrix tablets were prepared by direct compression technique. The investigation focused on the influence of modified polymer on water uptake behavior, mucoadhesive property and release rate of drug. Thiolated polymer increased the water uptake ratio and mucoadhesive property of the formulations. A new simple dissolution technique was developed to simulate the vaginal environment for the evaluation of release behavior of vaginal tablets. In this technique, daily production amount and rate of the vaginal fluid was used without any rotational movement. The drug release was found to be slower from PAA-Cys compared to that from PAA formulations. The similarity study results confirmed that the difference in particle size of EN and MN did not affect their release profile. The release process was described by plotting the fraction released drug versus time and n fitting data to the simple exponential model: M(t)/M(∞)=kt(n). The release kinetics were determined as Super Case II for all the formulations prepared with PAA or PAA-Cys. According to these results the mucoadhesive vaginal tablet formulations prepared with PAA-Cys represent good example for delivery systems which prolong the residence time of drugs at the vaginal mucosal surface.

Optical instrument for measurement of vaginal coating thickness by drug delivery formulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Henderson, Marcus H.; Peters, Jennifer J.; Walmer, David K.

2005-03-01

An optical device has been developed for imaging the human vaginal epithelial surfaces, and quantitatively measuring distributions of coating thickness of drug delivery formulations - such as gels - applied for prophylaxis, contraception or therapy. The device consists of a rigid endoscope contained within a 27-mm-diam hollow, polished-transparent polycarbonate tube (150 mm long) with a hemispherical cap. Illumination is from a xenon arc. The device is inserted into, and remains stationary within the vagina. A custom gearing mechanism moves the endoscope relative to the tube, so that it views epithelial surfaces immediately apposing its outer surface (i.e., 150 mm longmore » by 360 deg. azimuthal angle). Thus, with the tube fixed relative to the vagina, the endoscope sites local regions at distinct and measurable locations that span the vaginal epithelium. The returning light path is split between a video camera and photomultiplier. Excitation and emission filters in the light path enable measurement of fluorescence of the sited region. Thus, the instrument captures video images simultaneously with photometric measurement of fluorescence of each video field [{approx}10 mm diameter; formulations are labeled with 0.1% w/w United States Pharmacoepia (USP) injectable sodium fluorescein]. Position, time and fluorescence measurements are continuously displayed (on video) and recorded (to a computer database). The photomultiplier output is digitized to quantify fluorescence of the endoscope field of view. Quantification of the thickness of formulation coating of a surface sited by the device is achieved due to the linear relationship between thickness and fluorescence intensity for biologically relevant thin layers (of the order of 0.5 mm). Summary measures of coating have been developed, focusing upon extent, location and uniformity. The device has begun to be applied in human studies of model formulations for prophylaxis against infection with HIV and other sexually

Optical instrument for measurement of vaginal coating thickness by drug delivery formulations

NASA Astrophysics Data System (ADS)

Henderson, Marcus H.; Peters, Jennifer J.; Walmer, David K.; Couchman, Grace M.; Katz, David F.

2005-03-01

An optical device has been developed for imaging the human vaginal epithelial surfaces, and quantitatively measuring distributions of coating thickness of drug delivery formulations—such as gels—applied for prophylaxis, contraception or therapy. The device consists of a rigid endoscope contained within a 27-mm-diam hollow, polished-transparent polycarbonate tube (150mm long) with a hemispherical cap. Illumination is from a xenon arc. The device is inserted into, and remains stationary within the vagina. A custom gearing mechanism moves the endoscope relative to the tube, so that it views epithelial surfaces immediately apposing its outer surface (i.e., 150mm long by 360° azimuthal angle). Thus, with the tube fixed relative to the vagina, the endoscope sites local regions at distinct and measurable locations that span the vaginal epithelium. The returning light path is split between a video camera and photomultiplier. Excitation and emission filters in the light path enable measurement of fluorescence of the sited region. Thus, the instrument captures video images simultaneously with photometric measurement of fluorescence of each video field [˜10mm diameter; formulations are labeled with 0.1%w/w United States Pharmacoepia (USP) injectable sodium fluorescein]. Position, time and fluorescence measurements are continuously displayed (on video) and recorded (to a computer database). The photomultiplier output is digitized to quantify fluorescence of the endoscope field of view. Quantification of the thickness of formulation coating of a surface sited by the device is achieved due to the linear relationship between thickness and fluorescence intensity for biologically relevant thin layers (of the order of 0.5mm). Summary measures of coating have been developed, focusing upon extent, location and uniformity. The device has begun to be applied in human studies of model formulations for prophylaxis against infection with HIV and other sexually transmitted pathogens.

Circulating maternal cortisol levels during vaginal delivery and elective cesarean section.

PubMed

Stjernholm, Ylva Vladic; Nyberg, Annie; Cardell, Monica; Höybye, Charlotte

2016-08-01

Maternal S-cortisol levels increase throughout pregnancy and peak in the third trimester. Even higher levels are seen during the physical stress of delivery. Since analgesia for women in labor has improved, it is possible that maternal stress during labor is reduced. The aim of this study was to compare maternal S-cortisol during vaginal delivery and elective cesarean section. Twenty healthy women with spontaneous vaginal delivery and healthy women (n = 20) undergoing elective cesarean section were included in the study. S-cortisol was measured during three stages of spontaneous vaginal delivery (tvd1, tvd2 and tvd3), as well as before and after elective cesarean section (tcs1 and tcs2). In the vaginal delivery group, mean S-cortisol at tvd1 was 1325 ± 521 nmol/L, at tvd2 1559 ± 591 nmol/L and at tvd3 1368 ± 479 nmol/L. In the cesarean section group, mean S-cortisol at tcs1 was 906 ± 243 nmol/L and at tcs2 831 ± 257 nmol/L. S-cortisol was higher in the vaginal delivery group at the onset of labor as compared to the cesarean section preoperative group (p = 0.006). There were also significant differences between S-cortisol levels postpartum as compared to postoperatively (p < 0.001). Maternal S-cortisol was higher during vaginal delivery compared to elective cesarean section, indicating higher stress levels. A reduction in the hydrocortisone dose at childbirth in women with adrenal insufficiency should be considered, particularly in women undergoing an elective cesarean section.

Vaginal Cleansing Before Cesarean Delivery: A Systematic Review and Meta-analysis.

PubMed

Caissutti, Claudia; Saccone, Gabriele; Zullo, Fabrizio; Quist-Nelson, Johanna; Felder, Laura; Ciardulli, Andrea; Berghella, Vincenzo

2017-09-01

To assess the efficacy of vaginal cleansing before cesarean delivery in reducing postoperative endometritis. MEDLINE, Ovid, EMBASE, Scopus, Clinicaltrials.gov, and Cochrane Library were searched from their inception to January 2017. Selection criteria included all randomized controlled trials comparing vaginal cleansing (ie, intervention group) with a control group (ie, either placebo or no intervention) in women undergoing cesarean delivery. Any method of vaginal cleansing with any type of antiseptic solution was included. The primary outcome was the incidence of endometritis. Meta-analysis was performed using the random-effects model of DerSimonian and Laird to produce summary treatment effects in terms of relative risk (RR) with 95% CI. Sixteen trials (4,837 women) on vaginal cleansing immediately before cesarean delivery were identified as relevant and included in the review. In most of the included studies, 10% povidone-iodine was used as an intervention. The most common way to perform the vaginal cleansing was the use of a sponge stick for approximately 30 seconds. Women who received vaginal cleansing before cesarean delivery had a significantly lower incidence of endometritis (4.5% compared with 8.8%; RR 0.52, 95% CI 0.37-0.72; 15 studies, 4,726 participants) and of postoperative fever (9.4% compared with 14.9%; RR 0.65, 95% CI 0.50-0.86; 11 studies, 4,098 participants) compared with the control group. In the planned subgroup analyses, the reduction in the incidence of endometritis with vaginal cleansing was limited to women in labor before cesarean delivery (8.1% compared with 13.8%; RR 0.52, 95% CI 0.28-0.97; four studies, 440 participants) or those with ruptured membranes (4.3% compared with 20.1%; RR 0.23, 95% CI 0.10-0.52; three studies, 272 participants). Vaginal cleansing immediately before cesarean delivery in women in labor and in women with ruptured membranes reduces the risk of postoperative endometritis. Because it is generally inexpensive and a

Drugs Approved for Vaginal Cancer

Cancer.gov

This page lists cancer drugs approved by the Food and Drug Administration (FDA) to prevent vaginal cancer. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

Vaginal delivery among women who underwent labor induction with vaginal dinoprostone (PGE2) insert: a retrospective study of 1656 women in China.

PubMed

Zhao, Lei; Lin, Ying; Jiang, Ting-Ting; Wang, Ling; Li, Min; Wang, Ying; Sun, Guo-Qiang; Xiao, Mei

2017-12-21

This study aimed to qualify relevant factors for vaginal delivery among women who underwent labor induction with vaginal dinoprostone (PGE2) insert in a Chinese tertiary maternity hospital. A retrospective study was conducted in Hubei Maternal and Child Health Hospital. A total of 1656 pregnancies that underwent labor induction with vaginal dinoprostone insert between January and August 2016 were finally included in this study. Data were analyzed using univariate and multivariable regression modeling. Of 1656 women with PGE2-induced labor at term, 396 (23.91%) gave birth by cesarean section, 1260 (76.09%) had a vaginal delivery among which 921 (55.61%) delivered vaginally within 24 h. Multivariable regression analysis showed that maternal age (p < .001, OR = 0.89, 95%CI 0.85-0.93), parity (multiparous versus nulliparous, p < .001, OR = 8.74, 95%CI 4.36-17.50), baseline fetal heart rate (p = .009, OR = 0.98, 95%CI 0.96-0.99), and birth weight (p < .001, OR = 0.37, 95%CI 0.28-0.51) were significantly correlated with vaginal delivery. Moreover, body mass index (p < .001, OR = 1.11, 95%CI 1.05-1.19), parity (multiparous versus nulliparous, p < .001, OR = 6.57, 95%CI 2.37-18.23), baseline fetal heart rate (p = .004, OR = 0.96, 95%CI 0.94-0.99), and birth weight (p < .001, OR = 0.34, 95%CI 0.21-0.54) were independent predictors of vaginal delivery within 24-h. Our findings suggested a vaginal delivery rate of 76.09% when dinoprostone vaginal insert was used for labor induction, which was markedly higher than the overall annual vaginal delivery rate of 65.1% in China during 2014. Maternal age, parity, baseline fetal heart rate, and birth weight were significant factors for vaginal delivery. This study enables us to better understand the efficiency of dinoprostone and the potential predictors of vaginal delivery in dinoprostone-induced labor, which may be helpful to guide the clinical use of dinoprostone and therefore provide better

Novel engineered systems for oral, mucosal and transdermal drug delivery.

PubMed

Li, Hairui; Yu, Yuan; Faraji Dana, Sara; Li, Bo; Lee, Chi-Ying; Kang, Lifeng

2013-08-01

Technological advances in drug discovery have resulted in increasing number of molecules including proteins and peptides as drug candidates. However, how to deliver drugs with satisfactory therapeutic effect, minimal side effects and increased patient compliance is a question posted before researchers, especially for those drugs with poor solubility, large molecular weight or instability. Microfabrication technology, polymer science and bioconjugate chemistry combine to address these problems and generate a number of novel engineered drug delivery systems. Injection routes usually have poor patient compliance due to their invasive nature and potential safety concerns over needle reuse. The alternative non-invasive routes, such as oral, mucosal (pulmonary, nasal, ocular, buccal, rectal, vaginal), and transdermal drug delivery have thus attracted many attentions. Here, we review the applications of the novel engineered systems for oral, mucosal and transdermal drug delivery.

Administration of oral and vaginal prebiotic lactoferrin for a woman with a refractory vaginitis recurring preterm delivery: appearance of lactobacillus in vaginal flora followed by term delivery.

PubMed

Otsuki, Katsufumi; Tokunaka, Mayumi; Oba, Tomohiro; Nakamura, Masamitsu; Shirato, Nahoko; Okai, Takashi

2014-02-01

Lactoferrin (LF) is one of the prebiotics present in the human body. A 38-year-old multiparous woman with poor obstetrical histories, three consecutive preterm premature rupture of membrane at the 19th, 23rd and 25th week of pregnancy, was referred to our hospital. She was diagnosed as having refractory vaginitis. Although estriol vaginal tablets were used for 4 months, the vaginitis was not cured. We administrated vaginal tablets and oral agents of prebiotic LF, resulting in a Lactobacillus predominant vaginal flora. When she was pregnant, she continued to use the LF, and the Lactobacillus in the vaginal flora was continuously observed during pregnancy. An elective cesarean section was performed at the 38th week of pregnancy. When the administration of LF was discontinued after the delivery, Lactobacillus in the vaginal flora was disappeared. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

Broad Ligament Haematoma Following Normal Vaginal Delivery.

PubMed

Ibrar, Faiza; Awan, Azra Saeed; Fatima, Touseef; Tabassum, Hina

2017-01-01

A 37-year-old, patient presented in emergency with history of normal vaginal delivery followed by development of abdominal distention, vomiting, constipation for last 3 days. She was para 4 and had normal vaginal delivery by traditional birth attendant at peripheral hospital 3 days back. Imaging study revealed a heterogeneous complex mass, ascites, pleural effusion, air fluid levels with dilatation gut loops. Based upon pelvic examination by senior gynaecologist in combination with ultrasound; a clinical diagnosis of broad ligament haematoma was made. However, vomiting and abdominal distention raised suspicion of intestinal obstruction. Due to worsening abdominal distention exploratory laparotomy was carried out. It was pseudo colonic obstruction and caecostomy was done. Timely intervention by multidisciplinary approach saved patient life with minimal morbidity.

Women's Psychological Adjustment Following Emergency Cesarean versus Vaginal Delivery.

ERIC Educational Resources Information Center

Padawer, Jill A.; And Others

1988-01-01

Investigated psychological adjustment and satisfaction in women who had given birth vaginally or by cesarean section. Cesarean mothers reported significantly less satisfaction with the delivery than did vaginal mothers; however no differences were found in postpartum psychological adjustment as measured by depression, anxiety, and confidence in…

Effect of Rotation on Perineal Lacerations in Forceps-Assisted Vaginal Deliveries

PubMed Central

Bradley, Megan S.; Kaminski, Robert J.; Streitman, David C.; Dunn, Shannon L.; Krans, Elizabeth E.

2013-01-01

Objective To determine the difference in the rates of severe perineal lacerations between forceps-assisted vaginal deliveries in the occiput-posterior (OP) position compared with forceps-assisted vaginal deliveries in which the fetal head was rotated to occiput anterior (OA) prior to delivery. Methods We studied a retrospective cohort of 148 women who had a forceps-assisted vaginal delivery from 2008–2011 at the University of Pittsburgh. Mild perineal lacerations were defined as first or second degree, and severe lacerations were defined as third or fourth degree. Chi-square and t tests were used for bivariate and logistic regression was used for multivariable analyses. P<.05 was considered statistically significant. Results Of 148 forceps-assisted deliveries, 81 delivered OA after either manual or forceps rotation, 10 delivered in the OP or occiput-transverse position after an unsuccessful rotation, and 57 delivered OP without attempted rotation. No significant differences were found between demographic, obstetric and neonatal characteristics of the groups. Overall, 86 (67.7%) women had mild lacerations and 41 (32.3%) had severe lacerations. A significantly greater rate of severe perineal lacerations were found in the OP nonrotated compared with the rotated group (43.4% compared with 24.3%; P=.02). In multivariable analyses, adjusted for age, race, insurance, body mass index, gestational age, parity, episiotomy and neonatal weight, forceps-assisted vaginal delivery in the OP position without rotation remained significantly more likely to be associated with severe lacerations (OR 3.67; 95% CI 1.42–9.47). Conclusion Forceps-assisted vaginal delivery after rotation of an OP position to an OA position is associated with less severe maternal perineal trauma than forceps-assisted delivery in the OP position. PMID:23743462

Effect of rotation on perineal lacerations in forceps-assisted vaginal deliveries.

PubMed

Bradley, Megan S; Kaminski, Robert J; Streitman, David C; Dunn, Shannon L; Krans, Elizabeth E

2013-07-01

To determine the difference in the rates of severe perineal lacerations between forceps-assisted vaginal deliveries in the occiput-posterior position compared with forceps-assisted vaginal deliveries in which the fetal head was rotated to occiput-anterior before delivery. We studied a retrospective cohort of 148 women who had a forceps-assisted vaginal delivery from 2008 to 2011 at the University of Pittsburgh. Mild perineal lacerations were defined as first or second degree, and severe lacerations were defined as third or fourth degree. χ and t tests were used for bivariate and logistic regression was used for multivariable analyses. P<.05 was considered statistically significant. Of 148 forceps-assisted deliveries, 81 delivered occiput-anterior after either manual or forceps rotation, 10 delivered in the occiput-posterior or occiput-transverse position after an unsuccessful rotation, and 57 delivered occiput-posterior without attempted rotation. No significant differences were found among demographic, obstetric, and neonatal characteristics of the groups. Overall, 86 (67.7%) women had mild lacerations and 41 (32.3%) had severe lacerations. A significantly greater rate of severe perineal lacerations was found in the occiput-posterior nonrotated compared with the rotated group (43.4% compared with 24.3%; P=.02). In multivariable analyses, adjusted for age, race, insurance, body mass index, gestational age, parity, episiotomy, and birth weight, forceps-assisted vaginal delivery in the occiput-posterior position without rotation remained significantly more likely to be associated with severe lacerations (odds ratio 3.67, 95% confidence interval 1.42-9.47). Forceps-assisted vaginal delivery after rotation of an occiput-posterior position to an occiput-anterior position is associated with less severe maternal perineal trauma than forceps-assisted delivery in the occiput-posterior position. II.

Risk factors for the breakdown of perineal laceration repair after vaginal delivery.

PubMed

Williams, Meredith K; Chames, Mark C

2006-09-01

The purpose of this study was to identify risk factors that are associated with the breakdown of perineal laceration repair in the postpartum period. We conducted a retrospective, case-control study to review perineal laceration repair breakdown in patients who were delivered between September 1995 and February 2005 at the University of Michigan. Bivariate analysis with chi-square test and t-test and stepwise logistic regression analysis were performed. Fifty-nine cases and 118 control deliveries were identified from a total of 14,124 vaginal deliveries. Risk factors were longer second stage of labor (142 vs 87 minutes; P = .001), operative vaginal delivery (odds ratio, 3.6; 95% CI, 1.8-7.3), mediolateral episiotomy (odds ratio, 6.9; 95% CI, 2.6-18.7), third- or fourth-degree laceration (odds ratio, 3.1; 95% CI, 1.5-6.4), and meconium-stained amniotic fluid (odds ratio, 3.0; 95% CI, 1.1-7.9). Previous vaginal delivery was protective (odds ratio, 0.38; 95% CI, 0.18-0.84). Logistic regression showed the most significant factor to be an interaction between operative vaginal delivery and mediolateral episiotomy (odd ratio, 6.36; 95% CI, 2.18-18.57). The most significant events were mediolateral episiotomy, especially in conjunction with operative vaginal delivery, third- and fourth-degree lacerations, and meconium.

Microneedles as the technique of drug delivery enhancement in diverse organs and tissues.

PubMed

Rzhevskiy, Alexey S; Singh, Thakur Raghu Raj; Donnelly, Ryan F; Anissimov, Yuri G

2018-01-28

Microneedles is the technique of drug delivery enhancement, which was primarily designed for facilitating percutaneous drug delivery. Started from the development of simple solid microneedles, providing microporation of stratum corneum and therefore enhancement of topical drug delivery, for two decades the technique has progressed in various modifications such as hollow, coated, dissolving and hydrogel forming microneedles. In their turn, the modifications have resulted in new mechanisms of drug delivery enhancement and followed by the expansion of applicability range in terms of targeted tissues and organs. Thus, in addition to percutaneous drug delivery, microneedles have been considered as an efficient technique facilitating ocular, oral mucosal, gastrointestinal, ungual and vaginal drug administration. It is anticipated that the technique of microneedle-assisted drug delivery will soon become relevant for majority of organs and tissues. Copyright © 2017 Elsevier B.V. All rights reserved.

[Assessment of vacuum-assisted vaginal delivery in a frank breech presentation].

PubMed

Bleu, G; Deruelle, P; Demetz, J; Michel, S; Dufour, P; Depret, S; Subtil, D

2015-02-01

After verification of the eligibility criteria and with an obstetrician familiar with the specific maneuvers likely to be needed, vaginal delivery of breech presentations is possible. If problems arise during the active pushing phase of labor, vacuum extraction has been described in the literature for this uncommon condition with limited series. The aim of this study is to assess retrospectively vacuum extraction in frank breech presentation in our center. This retrospective study of trials of vaginal delivery of fetuses in breech presentation at term compares cases according to whether they did or did not use a vacuum extraction. During a two-year period, 83 patients, whom had trials of vaginal delivery in breech presentations, reached the active pushing/bearing down stage after complete cervical dilatation. Vacuum assistance was applied in six of these (7.2 %). The failure rate for vaginal delivery was significantly higher in the group with compared to without vacuum extraction (33.3 % versus 6.5 %, P<0.05). Moreover, the mean pH at birth was significantly lower in the group with vacuum extraction (7.12±0.11 versus 7.20±0.08, P<0.05), and these infants more frequently had deep cutaneous injuries (66.7 % versus 26.0 %, P<0.05). In fetuses in breech presentation, when vaginal delivery failed, it seems to be safer for the fetuses to perform caesarean section rather than attempt vacuum extraction. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Transient swelling, spreading, and drug delivery by a dissolved anti-HIV microbicide-bearing film

NASA Astrophysics Data System (ADS)

Tasoglu, Savas; Rohan, Lisa C.; Katz, David F.; Szeri, Andrew J.

2013-03-01

There is a widespread agreement that more effective drug delivery vehicles with more alternatives, as well as better active pharmaceutical ingredients (APIs), must be developed to improve the efficacy of microbicide products. For instance, in tropical regions, films are more appropriate than gels due to better stability of drugs at extremes of moisture and temperature. Here, we apply fundamental fluid mechanical and physicochemical transport theory to help better understand how successful microbicide API delivery depends upon properties of a film and the human reproductive tract environment. Several critical components of successful drug delivery are addressed. Among these are: elastohydrodynamic flow of a dissolved non-Newtonian film; mass transfer due to inhomogeneous dilution of the film by vaginal fluid contacting it along a moving boundary (the locally deforming vaginal epithelial surface); and drug absorption by the epithelium. Local rheological properties of the film are dependent on local volume fraction of the vaginal fluid. We evaluated this experimentally, delineating the way that constitutive parameters of a shear-thinning dissolved film are modified by dilution. To develop the mathematical model, we integrate the Reynolds lubrication equation with a mass conservation equation to model diluting fluid movement across the moving vaginal epithelial surface and into the film. This is a complex physicochemical phenomenon that is not well understood. We explore time- and space-varying boundary flux model based upon osmotic gradients. Results show that the model produces fluxes that are comparable to experimental data. Further experimental characterization of the vaginal wall is required for a more precise set of parameters and a more sophisticated theoretical treatment of epithelium.

W/O/W multiple emulsions containing nitroimidazole derivates for vaginal delivery.

PubMed

Ozer, Ozgen; Ozyazici, Mine; Tedajo, Muriel; Taner, Memduh S; Köseoglu, Kamil

2007-03-01

The aim of our study was to formulate a stable multiple emulsions containing two nitroimidazole derivates, metronidazole (MT) and ornidazole (OR), for vaginal therapy. MT and OR were located internal and external phases of multiple emulsion, respectively, and the in vitro release studies were realized in phosphate (pH 7) and lactate buffer (pH 4.5) solutions to investigate better the effect of pH and location of active substance on the release. The imaging studies were realized in rabbits following labeling MT and OR with Technethium-99m ((99m)Tc) to evaluate the in vivo absorption characteristics. The percentage of MT and OR released from the multiple emulsions in alkaline media were 3.2- and 2.8-fold greater than that observed in acidic media, respectively, when they were introduced in the internal phase of the multiple emulsions. The absorption rate of MT from vaginal epithelium was faster than OR. We observed that especially in alkaline medium a high release was found that was convenient for the vaginal infections seen in the alkaline pH. We concluded that W/O/W multiple emulsions were locally effective in vagina and they could be introduced as a new drug carrier system for vaginal delivery.

Maternal and fetal outcomes after uterine fundal pressure in spontaneous and assisted vaginal deliveries.

PubMed

Furrer, Romana; Schäffer, Leonhard; Kimmich, Nina; Zimmermann, Roland; Haslinger, Christian

2016-10-01

This study aimed to evaluate maternal and fetal outcomes after uterine fundal pressure (UFP) in spontaneous and assisted vaginal deliveries. In a retrospective cohort study, 9743 singleton term deliveries with cephalic presentation were analyzed from 2004 to 2013. Spontaneous and assisted vaginal deliveries were analyzed separately with and without the application of UFP. Odds ratios were adjusted in a multivariate logistic regression analysis. Prevalence of UFP was 8.9% in spontaneous and 12.1% in assisted vaginal deliveries. UFP was associated with a higher incidence of shoulder dystocia in both spontaneous (adjusted odds ratio [adj. OR] 2.44, confidence interval [CI] 95% 1.23-4.84) and assisted vaginal deliveries (adj. OR 6.88 CI 95% 3.50-13.53). Fetal acidosis (arterial umbilical pH<7.2) was seen more often after the application of UFP in spontaneous vaginal deliveries (adj. OR 3.18, CI 95% 2.64-3.82) and assisted vaginal deliveries (adj. OR 1.59 CI 95% 1.17-2.16). The incidence of 5'-Apgar<7 (adj. OR 2.19 CI 95% 1.04-4.6) and 10'-Apgar<7 (adj. OR 3.04 CI 95% 1.17-7.88) was also increased after the application of UFP in spontaneous deliveries. A higher incidence of anal sphincter tears (AST) (adj. OR 46.25 CI 95% 11.78-181.6) in the UFP group of spontaneous deliveries was observed. UFP is associated with increased occurrence of shoulder dystocia and fetal acidosis. In spontaneous deliveries, the risk for lower Apgar scores after 5 and 10 min is increased, as well as the risk for AST.

Studies and methodologies on vaginal drug permeation.

PubMed

Machado, Rita Monteiro; Palmeira-de-Oliveira, Ana; Gaspar, Carlos; Martinez-de-Oliveira, José; Palmeira-de-Oliveira, Rita

2015-09-15

The vagina stands as an important alternative to the oral route for those systemic drugs that are poorly absorbed orally or are rapidly metabolized by the liver. Drug permeation through the vaginal tissue can be estimated by using in vitro, ex vivo and in vivo models. The latter ones, although more realistic, assume ethical and biological limitations due to animal handling. Therefore, in vitro and ex vivo models have been developed to predict drug absorption through the vagina while allowing for simultaneous toxicity and pathogenesis studies. This review focuses on available methodologies to study vaginal drug permeation discussing their advantages and drawbacks. The technical complexity, costs and the ethical issues of an available model, along with its accuracy and reproducibility will determine if it is valid and applicable. Therefore every model shall be evaluated, validated and standardized in order to allow for extrapolations and results presumption, and so improving vaginal drug research and stressing its benefits. Copyright © 2015 Elsevier B.V. All rights reserved.

Neuraxial labor analgesia for vaginal delivery and its effects on childhood learning disabilities.

PubMed

Flick, Randall P; Lee, Kunmoo; Hofer, Ryan E; Beinborn, Charles W; Hambel, Ellen M; Klein, Melissa K; Gunn, Paul W; Wilder, Robert T; Katusic, Slavica K; Schroeder, Darrell R; Warner, David O; Sprung, Juraj

2011-06-01

In prior work, children born to mothers who received neuraxial anesthesia for cesarean delivery had a lower incidence of subsequent learning disabilities compared with vaginal delivery. The authors speculated that neuraxial anesthesia may reduce stress responses to delivery, which could affect subsequent neurodevelopmental outcomes. To further explore this possibility, we examined the association between the use of neuraxial labor analgesia and development of childhood learning disabilities in a population-based birth cohort of children delivered vaginally. The educational and medical records of all children born to mothers residing in the area of 5 townships of Olmsted County, Minnesota from 1976 to 1982 and remaining in the community at age 5 years were reviewed to identify those with learning disabilities. Cox proportional hazards regression was used to compare the incidence of learning disabilities between children delivered vaginally with and without neuraxial labor analgesia, including analyses adjusted for factors of either potential clinical relevance or that differed between the 2 groups in univariate analysis. Of the study cohort, 4684 mothers delivered children vaginally, with 1495 receiving neuraxial labor analgesia. The presence of childhood learning disabilities in the cohort was not associated with use of labor neuraxial analgesia (adjusted hazard ratio, 1.05; 95%confidence interval, 0.85-1.31; P = 0.63). The use of neuraxial analgesia during labor and vaginal delivery was not independently associated with learning disabilities diagnosed before age 19 years. Future studies are needed to evaluate potential mechanisms of the previous finding indicating that the incidence of learning disabilities is lower in children born to mothers via cesarean delivery under neuraxial anesthesia compared with vaginal delivery.

Association between vaginal birth after cesarean delivery and primary cesarean delivery rates.

PubMed

Rosenstein, Melissa G; Kuppermann, Miriam; Gregorich, Steven E; Cottrell, Erika K; Caughey, Aaron B; Cheng, Yvonne W

2013-11-01

To estimate the association between vaginal birth after cesarean delivery (VBAC) rates and primary cesarean delivery rates in California hospitals. Hospital VBAC rates were calculated using birth certificate and discharge data from 2009, and hospitals were categorized by quartile of VBAC rate. Multivariable logistic regression analysis was performed to estimate the odds of cesarean delivery among low-risk nulliparous women with singleton pregnancies at term in vertex presentation (nulliparous term singleton vertex) by hospital VBAC quartile while controlling for many patient-level and hospital-level confounders. There were 468,789 term singleton births in California in 2009 at 255 hospitals, 125,471 of which were low-risk nulliparous term singleton vertex. Vaginal birth after cesarean delivery rates varied between hospitals, with a range of 0-44.6%. Rates of cesarean delivery among low-risk nulliparous term singleton vertex women declined significantly with increasing VBAC rate. When adjusted for maternal and hospital characteristics, low-risk nulliparous term singleton vertex women who gave birth in hospitals in the highest VBAC quartile had an odds ratio of 0.55 (95% confidence interval 0.46-0.66) of cesarean delivery compared with women at hospitals with the lowest VBAC rates. Each percentage point increase in a hospital's VBAC rate was associated with a 0.65% decrease in the low-risk nulliparous term singleton vertex cesarean delivery rate. Hospitals with higher rates of VBAC have lower rates of primary cesarean delivery among low-risk nulliparous women with singleton pregnancies at term in vertex presentation. II.

Effect of epidural anaesthesia on clinician-applied force during vaginal delivery.

PubMed

Poggi, Sarah H; Allen, Robert H; Patel, Chirag; Deering, Shad H; Pezzullo, John C; Shin, Young; Spong, Catherine Y

2004-09-01

Epidural anesthesia (EA) is used in 80% of vaginal deliveries and is linked to neonatal and maternal trauma. Our objectives were to determine (1) whether EA affected clinician-applied force on the fetus and (2) whether this force influenced perineal trauma. After informed consent, multiparas with term, cephalic, singletons were delivered by 1 physician wearing a sensor-equipped glove to record force exerted on the fetal head. Those with EA were compared with those without for delivery force parameters. Regression analysis was used to identify predictors of vaginal laceration. The force required for delivery was greater in patients with EA (n = 27) than without (n = 5) (P < .01). Clinical parameters, including birth weight (P = .31) were similar between the groups. Clinician force was similar in those with no versus first- versus second-degree laceration (P = .5). Only birth weight was predictive of laceration (P = .02). Epidural use resulted in greater clinician force required for vaginal delivery of the fetus in multiparas, but this force was not associated with perineal trauma.

Maternal and neonatal copeptin levels at cesarean section and vaginal delivery.

PubMed

Foda, Ashraf A; Abdel Aal, Ibrahim A

2012-12-01

The objective of the study was to measure the copeptin levels in maternal serum and umbilical cord serum at cesarean section and vaginal delivery in normotensive pregnancy and pre-eclamptic women. This was a prospective study at Mansoura University Hospital, Egypt. Ninety cases were included. They were divided into six groups: (1) normal pregnancy near term, as a control group, (2) primiparas who had vaginal delivery, (3) primiparas who had vaginal delivery and mild preeclampsia, (4) elective repeat cesarean section, (5) intrapartum cesarean section for indications other than fetal distress, and (6) intrapartum cesarean section for fetal distress. Serum copeptin concentrations were quantified with an enzyme-linked immunosorbent assay (ELISA). Mean, standard deviation, and paired t-test were used to test for significant change in quantitative data. The vaginal delivery groups had higher levels of maternal serum copeptin than the elective cesarean section group (P<0.01). Higher maternal serum copeptin levels were found in cases with pre-eclampsia as compared with the normotensive cases. The maternal copeptin levels during intrapartum cesarean section were higher than that during elective repeat cesarean section. There was a significant correlation between maternal copeptin levels and the duration of the first stage. In the presence of fetal distress, umbilical cord serum copeptin levels were significantly higher than other groups. Vaginal delivery can be very painful and stressful, and is accompanied by a marked increase of maternal serum copeptin. Increased maternal levels of serum copeptin were found in cases with pre-eclampsia as compared with the normotensive cases, and it may be helpful in assessing the disease. Intrauterine fetal distress is a strong stimulus to the release of copeptin into the fetal circulation. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Maternal and neonatal outcomes of hospital vaginal deliveries in Tibet

PubMed Central

Miller, S; Tudor, C; Nyima; Thorsten, VR; Sonam; Droyoung; Craig, S; Le, P; Wright, LL; Varner, MW

2007-01-01

Introduction To determine the outcomes of vaginal deliveries in three study hospitals in Lhasa, Tibet Autonomous Region (TAR), People's Republic of China (PRC), at high altitude (3,650 m). Methods Prospective observational study of 1,121 vaginal deliveries. Results Pre-eclampsia/gestational hypertension (PE/GH) was the most common maternal complication 18.9% (n=212), followed by postpartum hemorrhage (blood loss ≥ 500 ml) 13.4%. There were no maternal deaths. Neonatal complications included: low birth weight (10.2%), small for gestational age (13.7%), preterm delivery (4.1%) and low Apgar (3.7%). There were 11 stillbirths (9.8/1,000 live births) and 19 early neonatal deaths (17/1,000 live births). Conclusion This is the largest study of maternal and newborn outcomes in Tibet. It provides information on the outcomes of institutional vaginal births among women delivering infants at high altitude. There was a higher incidence of PE/GH and low birth weight; rates of PPH were not increased compared to those at lower altitudes. PMID:17481630

Retention of Vaginal Breech Delivery Skills Taught in Simulation.

PubMed

Stone, Heather; Crane, Joan; Johnston, Kathy; Craig, Catherine

2018-02-01

The optimal frequency of conducting simulation training for high-acuity, low-frequency events in obstetrics and gynaecology residency programs is unknown. This study evaluated retention over time of vaginal breech delivery skills taught in simulation, by comparing junior and senior residents. In addition, the residents' subjective comfort level to perform this skill clinically was assessed. This prospective cohort study included 22 obstetrics and gynaecology residents in a Canadian residency training program. Digital recordings were completed for pre-training, immediate post-training, and delayed (10-26 weeks later) post-training intervals of a vaginal breech delivery simulation, with skill assessment by a blinded observer using a binary checklist. Residents also completed questionnaires to assess their subjective comfort level at each interval. Junior and senior residents had significant improvements in vaginal breech delivery skills from the pre-training assessment to both the immediate post-training assessment (junior, P <0.001; senior, P <0.001) and the delayed post-training assessment (P <0.001 and P = 0.001, respectively). There was a significant decline in skills between the immediate and delayed post-training sessions for junior and senior residents (P = 0.003 and P <0.001, respectively). Both junior and senior residents gained more comfort immediately after the training (P <0.001 and P <0.001, respectively), without a significant change between immediate post-training and delayed post-training comfort levels (P = 0.19 and P = 0.11, respectively). Residents retained vaginal breech delivery skills taught in simulation 10-26 weeks later, although a decline in skills occurred over this time period. Comfort level was positively affected and retained. These results will aid in determining the frequency of simulation teaching for high-acuity, low-frequency events in a residency simulation curriculum. Copyright © 2018 Society of

Safety of vaginal delivery among dichorionic diamniotic twins over 10 years in a UK teaching hospital.

PubMed

Rzyska, Ewelina; Ajay, Bini; Chandraharan, Edwin

2017-01-01

To determine whether vaginal delivery among dichorionic diamniotic twins remains a safe option following full implementation of the European Working Time Directive in the UK. A retrospective study was conducted using data for women with dichorionic diamniotic twin pregnancies who attended a teaching hospital in London, UK, for delivery between January 4, 2000, and December 23, 2010. Among 892 women, 474 (53.1%) attempted vaginal delivery, 220 (46.4%) of whom achieved spontaneous vaginal delivery of both twins. Instrumental vaginal delivery was performed among 89 women (18.8%), and 165 (34.8%) women underwent emergency cesarean delivery. Delivery of the second twin by emergency cesarean (n=31) was predominantly for fetal distress (13 [41.9%]) or abnormal lie (10 [32.3%]). A 5-minute Apgar score of 9 or 10 was recorded for 384 (83.7%) of 459 first twins and 369 (82.9%) of 445 second twins, irrespective of the mode of delivery. Vaginal delivery among dichorionic diamniotic twins had a good success rate and a low intrapartum emergency cesarean delivery rate. Training in cardiotocography and intrapartum procedures might further reduce the need for emergency cesarean delivery. © 2016 International Federation of Gynecology and Obstetrics.

Delivery mode and neonatal outcome after a trial of external cephalic version (ECV): a prospective trial of vaginal breech versus cephalic delivery.

PubMed

Reinhard, Joscha; Sänger, Nicole; Hanker, Lars; Reichenbach, Lena; Yuan, Juping; Herrmann, Eva; Louwen, Frank

2013-04-01

To examine the delivery mode and neonatal outcome after a trial of external cephalic version (ECV) procedures. This is an interim analysis of an ongoing larger prospective off-centre randomised trial, which compares a clinical hypnosis intervention against neuro-linguistic programming (NLP) of women with a singleton breech foetus at or after 37(0/7) (259 days) weeks of gestation and normal amniotic fluid index. Main outcome measures were delivery mode and neonatal outcome. On the same day after the ECV procedure two patients (2 %), who had unsuccessful ECVs, had Caesarean sections (one due to vaginal bleeding and one due to pathological CTG). After the ECV procedure 40.4 % of women had cephalic presentation (n = 38) and 58.5 % (n = 55) remained breech presentation. One patient remained transverse presentation (n = 1; 1.1 %). Vaginal delivery was observed by 73.7 % of cephalic presentation (n = 28), whereas 26.3 % (n = 10) had in-labour Caesarean sections. Of those, who selected a trial of vaginal breech delivery, 42.4 % (n = 14) delivered vaginally and 57.6 % (n = 19) delivered via Caesarean section. There is a statistically significant difference between the rate of vaginal birth between cephalic presentation and trial of vaginal breech delivery (p = 0.009), however, no difference in neonatal outcome was observed. ECV is a safe procedure and can reduce not only the rate of elective Caesarean sections due to breech presentation but also the rate of in-labour Caesarean sections even if a trial of vaginal breech delivery is attempted.

Spray-dried powders enhance vaginal siRNA delivery by potentially modulating the mucus molecular sieve structure.

PubMed

Wu, Na; Zhang, Xinxin; Li, Feifei; Zhang, Tao; Gan, Yong; Li, Juan

2015-01-01

Vaginal small interfering RNA (siRNA) delivery provides a promising strategy for the prevention and treatment of vaginal diseases. However, the densely cross-linked mucus layer on the vaginal wall severely restricts nanoparticle-mediated siRNA delivery to the vaginal epithelium. In order to overcome this barrier and enhance vaginal mucus penetration, we prepared spray-dried powders containing siRNA-loaded nanoparticles. Powders with Pluronic F127 (F127), hydroxypropyl methyl cellulose (HPMC), and mannitol as carriers were obtained using an ultrasound-assisted spray-drying technique. Highly dispersed dry powders with diameters of 5-15 μm were produced. These powders showed effective siRNA protection and sustained release. The mucus-penetrating properties of the powders differed depending on their compositions. They exhibited different potential of opening mesh size of molecular sieve in simulated vaginal mucus system. A powder formulation with 0.6% F127 and 0.1% HPMC produced the maximum increase in the pore size of the model gel used to simulate vaginal mucus by rapidly extracting water from the gel and interacting with the gel; the resulting modulation of the molecular sieve effect achieved a 17.8-fold improvement of siRNA delivery in vaginal tract and effective siRNA delivery to the epithelium. This study suggests that powder formulations with optimized compositions have the potential to alter the steric barrier posed by mucus and hold promise for effective vaginal siRNA delivery.

Neonatal morbidity associated with vaginal delivery of noncephalic second twins.

PubMed

Schmitz, Thomas; Korb, Diane; Battie, Catherine; Cordier, Anne-Gaël; de Carne Carnavalet, Céline; Chauleur, Céline; Equy, Véronique; Haddad, Bassam; Lemercier, Delphine; Poncelet, Christophe; Rigonnot, Luc; Goffinet, François

2018-04-01

Management of noncephalic second twin delivery rests on the results of population-based retrospective studies of twin births that have shown higher neonatal mortality and morbidity for second twins with noncephalic, compared with cephalic, presentations after vaginal delivery of the first twin. Because these studies are flawed by data of questionable validity, do not report the obstetrical practices at delivery, and do not allow collection of potential confounding variables, we performed a national prospective study specially designed to evaluate the management of twins' delivery. We sought to assess neonatal mortality and morbidity according to second twin presentation after vaginal birth of the first twin. The Jumeaux Mode d'Accouchement study was a nationwide prospective population-based cohort study of twin deliveries performed in 176 maternity units in France from February 2014 through March 2015. The primary outcome was a composite of intrapartum mortality and neonatal mortality and morbidity. Neonatal outcomes of second twins born ≥32 weeks of gestation after vaginal delivery of the first cephalic or breech twin were compared according to the noncephalic or cephalic second twin presentation. Multivariable logistic regression models controlled for potential confounders. Subgroup analyses were conducted according to the breech or transverse presentation of the noncephalic second twin, and gestational age at delivery, before or after 37 weeks of gestation. Among 3903 second twins enrolled in the study, 2384 (61.1%) were in cephalic and 1519 (38.9%) in noncephalic presentations, of whom 999 (25.6%) were in breech and 520 (13.3%) in transverse presentation. Composite neonatal mortality and morbidity did not differ between the noncephalic and cephalic group (47/1519 [3.1%] vs 59/2384 [2.5%]; adjusted odds ratio, 1.23; 95% confidence interval, 0.81-1.85). No significant difference between groups was shown for the primary outcome in subgroup analyses according to

Vaginal inserts based on chitosan and carboxymethylcellulose complexes for local delivery of chlorhexidine: preparation, characterization and antimicrobial activity.

PubMed

Bigucci, Federica; Abruzzo, Angela; Vitali, Beatrice; Saladini, Bruno; Cerchiara, Teresa; Gallucci, Maria Caterina; Luppi, Barbara

2015-01-30

The aim of this work was to prepare vaginal inserts based on chitosan/carboxymethylcellulose polyelectrolyte complexes for local delivery of chlorhexidine digluconate. Complexes were prepared with different chitosan/carboxymethylcellulose molar ratios at a pH value close to pKa interval of the polymers and were characterized in terms of physico-chemical properties, complexation yield and drug loading. Then complexes were used to prepare inserts as vaginal dosage forms and their physical handling, morphology, water-uptake ability and drug release properties as well as antimicrobial activity toward Candida albicans and Escherichia coli were evaluated. Results confirmed the ionic interaction between chitosan and carboxymethylcellulose and the influence of the charge amount on the complexation yield. Complexes were characterized by high values of drug loading and showed increasing water-uptake ability with the increase of carboxymethylcellulose amount. The selection of appropriate chitosan/carboxymethylcellulose molar ratios allowed to obtain cone-like shaped solid inserts, easy to handle and able to hydrate releasing the drug over time. Finally, the formulated inserts showed antimicrobial activity against common pathogens responsible for vaginal infections. Copyright © 2014 Elsevier B.V. All rights reserved.

Planned vaginal delivery versus Caesarean section for breech presentation in Ile-Ife, Nigeria.

PubMed

Orji, E O; Ajenifuja, K O

2003-11-01

The optimum mode of breech delivery remains a matter of controversy among obstetricians worldwide. To determine whether term breech babies born by planned vaginal delivery are at higher risk of neonatal mortality and morbidity than those born by planned caesarean delivery. A hospital based non-experimental comparison of outcome of breech delivery. Ife State Hospitals Complex, Ile-Ife. Two hundred and fourty four singleton breech deliveries occurring at term. They include low 5-minute Apgar score, birth trauma, maternal and perinatal morbidity and mortality. The perinatal mortality was not significantly different in both groups: OR 2.7 (95% C.I. 0.3-26.8). The low 5-minute Apgar scores were higher in the planned vaginal delivery OR 9.0 (95% C.I. 1-73.4), but the traumatic morbidity was not (OR 1.8, 95% C.I. 0.2-20.1). Maternal morbidity occurred more in the planned Caesarean delivery group OR 0.4 (95% C.I. 0.2-0.9). Given appropriate selection criteria and management protocol, the outcome from elective caesarean section might not be better than from planned vaginal delivery.

Management of patients with placenta accreta in association with fever following vaginal delivery

PubMed Central

Zhong, Liuying; Chen, Dunjin; Zhong, Mei; He, Yutian; Su, Chunhong

2017-01-01

Abstract This study aims to analyze the clinical characteristics and to manage patients with retained placenta left in situ accompanied by fever following vaginal delivery. Twenty-one patients with retained placenta in association with fever following vaginal delivery were enrolled and managed at the maternity department of our university hospital between 2012 and 2014. All patients had risk factors for development of placenta accreta: previous cesarean sections (4/21), previous curettage (15/21), or uterine malformations (7/21). Placenta accreta was diagnosed following vaginal delivery in all patients, and manual removal of the placenta was attempted in 20 of 21 patients. The placenta left in situ was partial in 19 patients and was complete in 2 patients. All patients were managed with a multidisciplinary approach. Mifepristone was administrated to 16 patients. Fourteen patients received uterine artery embolization. Eleven patients were treated with ultrasound-guided curettage within 24 hours following delivery. Seven patients needed delayed-hysterectomy due to development of complications. Intrauterine operations during labor are not recommended if placenta accreta occurs in the fundus and/or in the cornual region of the uterus. Antibiotic treatment, interventional therapy, and ultrasound-guided curettage within 24 hours following vaginal delivery are the recommended conservative management strategies. PMID:28272244

Spontaneous Caecal Perforation Associated with Ogilvie's Syndrome Following Vaginal Delivery - A Case Report.

PubMed

E, Harish; Vk, Sundeep; Kola, Sivasai Krishnaprasad; Kg, Dharma Kumar

2014-06-01

Acute pseudo-obstruction of the large bowel, Ogilvie's syndrome, can occur in the postpartum period following caesarean section which can result in caecal dilatation and may progress to perforation. This is quiet rare following normal vaginal delivery. Only two previous reports have been found in the English literature. We report a case of Ogilvie's syndrome with caecal perforation following normal vaginal delivery.

Comparison of Breast Crawl Between Infants Delivered by Vaginal Delivery and Cesarean Section.

PubMed

Heidarzadeh, Mohammad; Hakimi, Sevil; Habibelahi, Abbas; Mohammadi, Marzieh; Shahrak, Shakiba Pourasad

2016-05-12

Exclusive breastfeeding is the single most cost-effective intervention to reduce infant mortality. Breast crawl (BC) is deemed a natural way for the baby to behave immediately after delivery. BC is the method that may help initiation of breastfeeding in the most natural way. The aim of this study is to compare successful BC between neonates born through vaginal delivery and those born through cesarean section (CS) and factors associated with a positive outcome. Participants were mothers who delivered their babies during the period of October 2012 to December 2013 in Alzahra Hospital in Tabriz, through cesarean or vaginal delivery. Infants were placed prone on their mothers' abdomen after delivery. Data show that babies delivered through vaginal delivery had significantly more success in BC than babies born through the cesarean delivery (88.01% versus 11.21%). Moreover, babies in the CS group used significantly less time to achieve BC (45 versus 28 minutes). There is a remarkable difference in completion and length of time used to achieve BC between infants with regard to the delivery mode. Encouraging BC in all dyads, especially in cesarean births, may unduly delay the infant's first breastfeed.

Risk of Intrapartum Cervical Lacerations in Vaginal Singleton Deliveries in Women With Cerclage

PubMed Central

Suzuki, Shunji

2015-01-01

Background We examined the obstetric outcomes of singleton vaginal deliveries in women with cerclage at our institute to confirm the risk of intrapartum cervical lacerations in vaginal deliveries of women with cerclage. Methods Data on all Japanese singleton vaginal deliveries at ≥ 34 weeks’ gestation managed at the Japanese Red Cross Katsushika Maternity Hospital between 2008 and 2014 were collected. Results During the study period, cervical cerclage was performed in 95 of 9,490 (1.0%) women with singleton pregnancy at 12 - 22 weeks of singleton pregnancy who delivered at ≥ 34 weeks’ gestation. The incidence of intrapartum cervical lacerations and postpartum hemorrhage ≥ 1,000 mL in the women with cerclage were higher significantly than that in the women without cerclage (cervical lacerations: crude odds ratio (OR): 26.9, 95% confidence interval (CI): 14 - 51, P < 0.01; postpartum hemorrhage: crude OR: 2.86, 95% CI: 1.6 - 4.9, P < 0.01). Using a multivariate analysis, cerclage was independently associated with the increased incidence of intrapartum cervical lacerations (P < 0.01). Conclusions Cervical cerclage is an independent risk factor of intrapartum cervical lacerations in vaginal deliveries. PMID:26251687

A Comparison of Vaginal Pressures and Abdominal Muscle Thickness According to Childbirth Delivery Method during the Valsalva Maneuver

PubMed Central

Kim, Haroo; Kak, Hwang-Bo; Kim, Boin

2014-01-01

[Purpose] The purpose of this study was to compare the effect of childbirth delivery method on vaginal pressure and abdominal thickness during the Valsalva maneuver (VAL). [Subjects] Thirty healthy female volunteers (26–39 years of age) were selected for this research. Their delivery histories were: nulliparous 10, vaginal delivery 10, and Cesarean delivery 10. None of the participants had a history of incontinence. [Methods] In the crook-lying position, a perineometer probe was inserted into the vagina and the transducer was placed transversely on the right side of the body during the Valsalva maneuver. [Results] There were significant differences in the thickness of the transverses abdominis (TrA) between in all the groups rest and the Valsalva maneuver, and there were significant differences in the internus oblique (IO) in the nulliparous group. During the Valsalva maneuver, there were significant differences in the TrA between the nulliparous group and the vaginal delivery group, and there were significant differences in the IO between the nulliparous delivery group and the vaginal delivery group, and between the nulliparous group and the Cesarean section group. Delivery history changed vaginal pressure, and there were significant differences between the nulliparous group and the vaginal delivery group, and between the nulliparous group and the Cesarean delivery group. [Conclusion] Pregnancy and delivery method may affect pelvic floor and abdominal muscles during the Valsalva maneuver. PMID:24707104

Comparison of Apgar scores in breech presentations between vaginal and cesarean delivery

PubMed Central

Fajar, Jonny Karunia; Andalas, Mohd; Harapan, Harapan

2017-01-01

Objective: The mode of delivery in breech presentation (BP) is controversial. Several studies have reported the advantages and disadvantages of delivery mode in BP. The aim of this study was to compare the Apgar scores in BPs between vaginal and cesarean delivery. Materials and Methods: A retrospective study was conducted at Dr. Zainoel Abidin General Hospital from January 2010 to December 2012. Data on the mode of delivery and Apgar scores at 1 and 5 min for infants with a BP were extracted from the medical records. Logistic regression was employed to assess the correlation between mode of delivery and Apgar scores. In addition, a meta-analysis was conducted to summarize findings from other regions. Results: A total of 205 (3.9%) BPs among 5252 deliveries between January 2010 and December 2012 were analyzed for this study. There were 26% (52 cases) vaginal and 74% (153 cases) cesarean deliveries. The mode of delivery for BP had a significant association with Apgar score at 1 min (odds ratio [OR] 95% confidence interval [CI] = 6.462 [2.476–16.870], P = 0.0001) and 5 min (OR 95% CI = 7.727 [1.416–42.175], P = 0.018). Our meta-analysis showed that the delivery mode had a significant association with Apgar score in BP (OR: 3.69; 95% CI: 2.18–6.26, P = 0.0001). Conclusions: There was a significant association between Apgar scores in BPs and mode of delivery. Our results suggest better outcomes for cesarean than vaginal delivery in BPs. PMID:28757760

Perinatal and maternal morbidity and mortality after attempted operative vaginal delivery at midpelvic station

PubMed Central

Muraca, Giulia M.; Sabr, Yasser; Lisonkova, Sarka; Skoll, Amanda; Brant, Rollin; Cundiff, Geoffrey W.; Joseph, K.S.

2017-01-01

BACKGROUND: Increased use of operative vaginal delivery (i.e., forceps or vacuum application), of which 20% occurs at midpelvic station, has been advocated to reduce the rate of cesarean delivery. We aimed to quantify severe perinatal and maternal morbidity and mortality associated with attempted midpelvic operative vaginal delivery. METHODS: We studied all term singleton deliveries in Canada between 2003 and 2013, by attempted midpelvic operative vaginal or cesarean delivery with labour (with and without prolonged second stage). The primary outcomes were composite severe perinatal morbidity and mortality (e.g., convulsions, assisted ventilation, severe birth trauma and perinatal death), and composite severe maternal morbidity and mortality (e.g., severe postpartum hemorrhage, shock, sepsis, cardiac complications, acute renal failure and death). RESULTS: The study population included 187 234 deliveries. Among women with dystocia and prolonged second stage of labour, midpelvic operative vaginal delivery was associated with higher rates of severe perinatal morbidity and mortality compared with cesarean delivery (forceps, adjusted odds ratio [AOR] 1.81, 95% confidence interval [CI] 1.24 to 2.64; vacuum, AOR 1.81, 95% CI 1.17 to 2.80; sequential instruments, AOR 3.19, 95% CI 1.73 to 5.88), especially with higher rates of severe birth trauma. Rates of severe maternal morbidity and mortality were not significantly different after operative vaginal delivery, although rates of obstetric trauma were higher (forceps, AOR 4.51, 95% CI 4.04 to 5.02; vacuum, AOR 2.70, 95% CI 2.35 to 3.09; sequential instruments, AOR 4.24, 95% CI 3.46 to 5.19). Among women with fetal distress, similar associations were seen for severe birth trauma and obstetric trauma, although vacuum was associated with lower rates of severe maternal morbidity and mortality (AOR 0.52, 95% CI 0.33 to 0.80). Associations tended to be stronger among women without a prolonged second stage. INTERPRETATION: Midpelvic

The Costs and Their Determinant of Cesarean Section and Vaginal Delivery: An Exploratory Study in Chongqing Municipality, China

PubMed Central

He, Zhifei; Cheng, Zhaohui; Wu, Tailai; Zhou, Yan; Chen, Junguo; Fu, Qian

2016-01-01

Objectives. This study aims to analyze the cesarean section (CS) rates and vaginal delivery rates in tertiary hospitals of China, explore the costs of two different deliveries, and examine the relative influencing factors of the costs in both CS and vaginal deliveries. Methods. 30,168 anonymized obstetric medical cases were selected from three sample tertiary hospitals in Chongqing Municipality from 2011 to 2013. Chi-square test was used to compare the distributions of CS and vaginal deliveries under different indicators. Mann–Whitney test and Kruskal-Wallis test were adopted to analyze the differences under different items. Multiple linear regression was used to determine the influencing factors of the costs of different delivery modes. Results. (1) The rates of CS were 69%, 65.5%, and 59.2% in the three sample tertiary hospitals in Chongqing from 2011 to 2013. (2) The costs and the length of stay of CS were greater than those of vaginal delivery, which had significant differences (P < 0.005). (3) The areas, length of stay, age, medical insurance, and modes of delivery were the influencing factors of both CS and vaginal delivery costs. Discussion. The high CS rates in China must be paid significant attention. The indicators of two modes of delivery should be regulated strictly. CS rate reduction and saving medical resources will be the benefits if vaginal delivery is chosen by pregnant women. PMID:27995142

The optimal mode of delivery for the haemophilia carrier expecting an affected infant is vaginal delivery.

PubMed

Ljung, R

2010-05-01

The optimal mode of delivery of a haemophilia carrier expecting a child is still a matter of uncertainty and debate. The aim of this commentary/review is to suggest that normal vaginal delivery should be the recommended mode of delivery for the majority of carriers, based on review of studies on obstetric aspects of haemophilia. About 2.0-4.0% of all haemophilia boys born in countries with a good standard of health care will suffer from ICH during the neonatal period. This is an average figure including all modes of delivery and regardless of whether the carrier status of the mother or the haemophilia status of the foetus was known or not at the time of delivery. On the basis of current literature, one may conclude that the risk of serious bleeding in the neonate affected with haemophilia is small in conjunction with normal vaginal delivery. It should be possible to further reduce the low frequency of complications if appropriate precautions are taken when planning the delivery in pregnant woman with known carrier status, if the sex of the foetus is known and, even more, when the haemophilia status of the foetus is known. Instrumental delivery such as use of vacuum extraction and foetal scalp monitors must be avoided at delivery of carriers.

The frequent shift to intermediate flora in preterm delivery cases after abnormal vaginal flora screening

PubMed Central

Honda, Hiroshi; Yokoyama, Takanori; Akimoto, Yumiko; Tanimoto, Hirotoshi; Teramoto, Mitsue; Teramoto, Hideki

2014-01-01

The effect of screening and treatment for abnormal vaginal flora on the reduction of preterm deliveries remains controversial. We evaluated whether this screening and treatment reduces the preterm delivery rate for general-population pregnant women. Pregnant women of the Intervention group (n = 574) underwent the screening test and the treatment of vaginal metronidazole during the early second trimester, and those of the Control group (n = 1,161) did not. We compared the preterm delivery rate between these two groups. We also compared the profiles of vaginal flora of the preterm delivery cases with those of the pregnant women with a normal course. There was no significant difference in the preterm delivery rate between these two groups. However, in the preterm delivery cases, a frequent shift to intermediate flora was observed not before but after the screening in the Intervention group. This shift may explain why most of the previous studies failed in regard to the prevention of preterm deliveries. PMID:24762852

Intrapartum ultrasound: A useful method for evaluating labor progress and predicting operative vaginal delivery

PubMed Central

Ahn, Ki Hoon

2014-01-01

The last step of a successful pregnancy is the safe delivery of the fetus. An important question is if the delivery should vaginal or operative. In addition to the use of conventional antenatal ultrasound, the use of intrapartum ultrasound to evaluate fetal head station, position, cervical ripening, and placental separation is promising. This review evaluates and summarizes the usefulness of intrapartum ultrasound for the evaluation of labor progress and predicting successful operative vaginal delivery. PMID:25469329

Vaginal ring delivery of selective progesterone receptor modulators for contraception

PubMed Central

Jensen, Jeffrey T.

2013-01-01

Vaginal ring delivery of selective progesterone receptor modulators (SPRMs) are under development to address limitations of current hormonal methods that affect use and effectiveness. This method would be appropriate for use in women with contraindications to, or preferences to avoid, estrogens. A contraceptive vaginal ring (CVR) also eliminates the need for daily dosing, and therefore might improve the effectiveness of contraception. The principle contraceptive effect of SPRMs is the suppression of ovulation. One limiting factor of chronic SPRM administration is the development of benign endometrial thickening characterized as PRM-associated endometrial changes. Ulipristal acetate is approved for use as an emergency contraceptive pill, but no SPRM is approved for regular contraception. The Population Council is developing an ulipristal acetate CVR for regular contraception. The CVR studied is of a matrix design composed of micronized UPA mixed in a silicone rubber matrix The target product is a ring designed for continuous use over 3 months delivering near steady-state drug levels that will suppress ovulation. Results from Phase 1–2 studies demonstrate that suppression of ovulation occurs with UPA levels above 6–7 ng/mL. PMID:23040126

Expanding the domain of drug delivery for HIV prevention: exploration of the transdermal route.

PubMed

Puri, Ashana; Sivaraman, Arunprasad; Zhang, Wei; Clark, Meredith R; Banga, Ajay K

2017-01-01

Constant efforts for HIV prevention using antiretroviral drugs, pre- and postexposure prophylactic agents, and microbicides are being made by researchers. Drug-delivery systems such as oral tablets and coitally dependent vaginal gels are short acting, require daily application, and are associated with user adherence issues, whereas the coitally independent systems such as injectables and biodegradable implants are long acting, lasting several months, during which time the termination of prophylaxis is impractical in case of adverse effects. An effective drug-delivery system to be used for an intermediate duration, if available, would be an attractive alternative option for users in terms of adherence. Transdermal delivery systems, overcoming most of the limitations of the other routes of administration and aiming to provide sustained delivery of drugs through skin, may be explored for HIV prevention. Passive and physical enhancement techniques may be designed strategically to improve the transdermal delivery of HIV preventive agents.

Comparison of Reproductive Outcomes following Retained Products of Conception after Vaginal Delivery versus First-Trimester Abortion.

PubMed

Melcer, Yaakov; Smorgick, Noam; Schneider, David; Pansky, Moty; Halperin, Reuvit; Ben-Ami, Ido

2015-01-01

To compare the reproductive outcomes of women with pathologically confirmed retained products of conception (RPOC) following spontaneous vaginal delivery versus first-trimester pregnancy termination. We retrospectively reviewed all cases of women who underwent uterine re-evacuation due to pathologically confirmed RPOC between January 1, 2000 and December 31, 2010. Reproductive outcomes were compared between women with RPOC following spontaneous vaginal delivery and those who underwent dilatation and curettage (D&C) due to first-trimester abortion. The study group consisted of 176 patients with pathologically confirmed RPOC. Of those, 83 (47.1%) were admitted after spontaneous vaginal delivery and 93 (52.9%) following D&C due to first-trimester abortion. There were no significant differences in the conception rate, the mean time to conception and the rate of a new infertility problem between women with RPOC after vaginal delivery compared to those following pregnancy termination (p > 0.05). Furthermore, there were no significant differences between the groups in pregnancy outcomes following RPOC. Pathologically confirmed RPOC harbors the same reproductive outcomes following spontaneous vaginal delivery and first-trimester pregnancy termination. © 2015 S. Karger AG, Basel.

Anal incontinence after two vaginal deliveries without obstetric anal sphincter rupture.

PubMed

Persson, Lisa K G; Sakse, Abelone; Langhoff-Roos, Jens; Jangö, Hanna

2017-06-01

To evaluate prevalence and risk factors for long-term anal incontinence in women with two prior vaginal deliveries without obstetric anal sphincter injury (OASIS) and to assess the impact of anal incontinence-related symptoms on quality of life. This is a nation-wide cross-sectional survey study. One thousand women who had a first vaginal delivery and a subsequent delivery, both without OASIS, between 1997 and 2008 in Denmark were identified in the Danish Medical Birth Registry. Women with more than two deliveries in total till 2012 were excluded at this stage. Of the 1000 women randomly identified, 763 were eligible and received a questionnaire. Maternal and obstetric data were retrieved from the national registry. The response rate was 58.3%. In total, 394 women were included for analysis after reviewing responses according to previously defined exclusion criteria. Median follow-up time was 9.8 years after the first delivery and 6.4 years after the second. The prevalence of flatal incontinence, fecal incontinence and fecal urgency were 11.7, 4.1, and 12.3%, respectively. Overall, 20.1% had any degree of anal incontinence and/or fecal urgency. In 6.3% these symptoms affected their quality of life. No maternal or obstetric factors including episiotomy and vacuum extraction were consistently associated with altered risk of anal incontinence in the multivariable analyses. Anal incontinence and fecal urgency is reported by one fifth of women with two vaginal deliveries without OASIS at long-term follow-up. Episiotomy or vacuum extraction did not alter the risk of long-term anal incontinence.

Characteristics Associated With Severe Perineal and Cervical Lacerations During Vaginal Delivery

PubMed Central

Landy, Helain J.; Laughon, S. Katherine; Bailit, Jennifer; Kominiarek, Michelle A.; Gonzalez-Quintero, Victor Hugo; Ramirez, Mildred; Haberman, Shoshana; Hibbard, Judith; Wilkins, Isabelle; Branch, D. Ware; Burkman, Ronald T.; Gregory, Kimberly; Hoffman, Matthew K.; Learman, Lee A.; Hatjis, Christos; VanVeldhuisen, Paul C.; Reddy, Uma M.; Troendle, James; Sun, Liping; Zhang, Jun

2011-01-01

Objective To characterize potentially modifiable risk factors for third- or fourth-degree perineal lacerations and cervical lacerations in a contemporary U.S. obstetric practice. Methods The Consortium on Safe Labor collected electronic medical records from 19 hospitals within 12 institutions (228,668 deliveries from 2002 to 2008). Information on patient characteristics, prenatal complications, labor and delivery data, and maternal and neonatal outcomes were collected. Only women with successful vaginal deliveries of cephalic singletons at 34 weeks of gestation or later were included; we excluded data from sites lacking information about lacerations at delivery and deliveries complicated by shoulder dystocia; 87,267 and 71,170 women were analyzed for third- or fourth-degree and cervical lacerations, respectively. Multivariable logistic regressions were used to adjust for other factors. Results Third- or fourth-degree lacerations occurred in 2,516 women (2,223 nulliparous [5.8%], 293 [0.6%] multiparous) and cervical lacerations occurred in 536 women (324 nulliparous [1.1%], 212 multiparous [0.5%]). Risks for third or fourth-degree lacerations included nulliparity (7.2-fold risk), being Asian or Pacific Islander, increasing birth weight, operative vaginal delivery, episiotomy, and longer second stage of labor. Increasing body mass index was associated with fewer lacerations. Risk factors for cervical lacerations included young maternal age, vacuum vaginal delivery, and oxytocin use among multiparous women, and cerclage regardless of parity. Conclusion Our large cohort of women with severe obstetric lacerations reflects contemporary obstetric practices. Nulliparity and episiotomy use are important risk factors for third- or fourth-degree lacerations. Cerclage increases the risk for cervical lacerations. Many identified risk factors may not be modifiable. PMID:21343766

Carbetocin versus oxytocin for prevention of postpartum hemorrhage after vaginal delivery in high risk women.

PubMed

Maged, Ahmed Mohamed; Hassan, AbdelGany M A; Shehata, Nesreen A A

2016-01-01

To compare effectiveness and tolerability of carbetocin versus oxytocin in prevention of postpartum hemorrhage (PPH) after vaginal delivery. A prospective double-blinded randomized study conducted on 200 pregnant women randomized into two groups: Group 1 (100 women) received single 100 μg IM dose of carbetocin and Group 2 received of 5 IU oxytocin IM. Both groups received their drug after fetal and before placental delivery. There was a statistically significant difference between the two study groups regarding amount of bleeding (337.73 ± 118.77 versus 378 ± 143.2), occurrence of PPH (4 versus 16%), need for other uterotonics (23 versus 37%) and hemoglobin difference between before and after delivery (0.55 ± 0.35 versus 0.96 ± 0.62) (all being lower in carbetocin group) and measured hemoglobin 24 h after delivery (being higher in carbetocin group); however, there was no significant difference between the two study groups regarding occurrence of major PPH and the need for blood transfusion. Women in carbetocin group showed a statistically significant lower systolic and diastolic blood pressure immediately after delivery and at 30 and 60 min than women in oxytocin group. There was no significant difference between the two study groups regarding occurrence of nausea, vomiting, flushing, dizziness, headache, shivering, metallic taste, dyspnea, palpitation and itching. Women in carbetocin group experienced tachycardia more than women in oxytocin group. Carbitocin is a better alternative to traditional oxytocin in prevention of PPH after vaginal delivery with minimal hemodynamic changes and similar side effects.

Nanoparticle-releasing nanofiber composites for enhanced in vivo vaginal retention.

PubMed

Krogstad, Emily A; Ramanathan, Renuka; Nhan, Christina; Kraft, John C; Blakney, Anna K; Cao, Shijie; Ho, Rodney J Y; Woodrow, Kim A

2017-11-01

Current approaches for topical vaginal administration of nanoparticles result in poor retention and extensive leakage. To overcome these challenges, we developed a nanoparticle-releasing nanofiber delivery platform and evaluated its ability to improve nanoparticle retention in a murine model. We individually tailored two components of this drug delivery system for optimal interaction with mucus, designing (1) mucoadhesive fibers for better retention in the vaginal tract, and (2) PEGylated nanoparticles that diffuse quickly through mucus. We hypothesized that this novel dual-functioning (mucoadhesive/mucus-penetrating) composite material would provide enhanced retention of nanoparticles in the vaginal mucosa. Equivalent doses of fluorescent nanoparticles were vaginally administered to mice in either water (aqueous suspension) or fiber composites, and fluorescent content was quantified in cervicovaginal mucus and vaginal tissue at time points from 24 h to 7d. We also fabricated composite fibers containing etravirine-loaded nanoparticles and evaluated the pharmacokinetics over 7d. We found that our composite materials provided approximately 30-fold greater retention of nanoparticles in the reproductive tract at 24 h compared to aqueous suspensions. Compared to nanoparticles in aqueous suspension, the nanoparticles in fiber composites exhibited sustained and higher etravirine concentrations after 24 h and up to 7d, demonstrating the capabilities of this new delivery platform to sustain nanoparticle release out to 3d and drug retention out to one week after a single administration. This is the first report of nanoparticle-releasing fibers for vaginal drug delivery, as well as the first study of a single delivery system that combines two components uniquely engineered for complementary interactions with mucus. Copyright © 2017 Elsevier Ltd. All rights reserved.

The significance of peripartum fever in women undergoing vaginal deliveries.

PubMed

Bensal, Adi; Weintraub, Adi Y; Levy, Amalia; Holcberg, Gershon; Sheiner, Eyal

2008-10-01

We investigated whether patients undergoing vaginal delivery who developed peripartum fever (PPF) had increased rates of other gestational complications. A retrospective study was undertaken comparing pregnancy complications of patients who developed PPF with those who did not. A multivariable logistic regression model was constructed to control for confounders. To avoid ascertainment bias, the year of birth was included in the model. Women who underwent cesarean delivery and those with multiple pregnancies were excluded from the study. During the study period, there were 169,738 singleton vaginal deliveries, and 0.4% of the women suffered from PPF. Hypertensive disorders, induction of labor, dystocia of labor in the second stage, suspected fetal distress, meconium-stained amniotic fluid, postpartum hemorrhage, manual lysis of a retained placenta, and revision of the uterine cavity and cervix were found to be independently associated with PPF by multivariable analysis. Year of birth was found to be a risk factor for fever. Apgar scores lower than 7 at 1 but not 5 minutes were significantly higher in the PPF group. Perinatal mortality rates were significantly higher among women with PPF (6.7% versus 1.3%, odds ratio [OR] = 5.4; 95% confidence interval [CI] 3.9 to 7.3; P < 0.001). Using another multivariable analysis, with perinatal mortality as the outcome variable, PPF was found as an independent risk factor for perinatal mortality (OR = 2.9; 95% CI 1.9 to 4.6; P < 0.001). PPF in women undergoing vaginal deliveries is associated with adverse perinatal outcomes and specifically is an independent risk factor for perinatal mortality.

The incidence and risk factors for retained placenta after vaginal delivery - a single center experience.

PubMed

Ashwal, Eran; Melamed, Nir; Hiersch, Liran; Wiznitzer, Arnon; Yogev, Yariv; Peled, Yoav

2014-12-01

We aimed to determine the incidence and risk factors for retained placenta immediately after vaginal delivery in a single, university-affiliated tertiary center. A case-control study. Women who delivered vaginally and diagnosed with suspected retained placenta were compared to control group of women with spontaneous vaginal delivery with spontaneous non-complicated placental separation between the years 2007 and 2012. Eligibility was limited to singleton fetuses in vertex presentation with no history of more than one cesarean section, stillbirth or major fetal anomaly. Overall, 33,925 women delivered vaginally, of them, 491 (1.4%) underwent revision of uterine cavity due to suspected retained placenta. Women with retained placenta were characterized by a higher rate of previous cesarean section (OR 1.71, 95% CI 1.23-2.36), previous abortions, lower parity (OR 0.79, 95% CI 0.68-0.91), lower gestational age at delivery. Hypertensive disorders, oligohydramnios and labor and delivery interventions as induction of labor (OR 1.84, 95% CI 1.30-2.59), neuro-axial analgesia (OR 1.60, 95% CI 1.27-2.00) and vacuum delivery (OR 1.89, 95% CI 1.48-2.41) were independently associated with uterine revision for retained placenta. Risk factors for manual revision due to retained placenta can be recognized. This data should be taken into consideration in the assessment of women immediately after delivery.

In Situ Forming Polymeric Drug Delivery Systems

PubMed Central

Madan, M.; Bajaj, A.; Lewis, S.; Udupa, N.; Baig, J. A.

2009-01-01

In situ forming polymeric formulations are drug delivery systems that are in sol form before administration in the body, but once administered, undergo gelation in situ, to form a gel. The formation of gels depends on factors like temperature modulation, pH change, presence of ions and ultra violet irradiation, from which the drug gets released in a sustained and controlled manner. Various polymers that are used for the formulation of in situ gels include gellan gum, alginic acid, xyloglucan, pectin, chitosan, poly(DL-lactic acid), poly(DL-lactide-co-glycolide) and poly-caprolactone. The choice of solvents like water, dimethylsulphoxide, N-methyl pyrrolidone, triacetin and 2-pyrrolidone for these formulations depends on the solubility of polymer used. Mainly in situ gels are administered by oral, ocular, rectal, vaginal, injectable and intraperitoneal routes. The in situ gel forming polymeric formulations offer several advantages like sustained and prolonged action in comparison to conventional drug delivery systems. The article presents a detailed review of these types of polymeric systems, their evaluation, advancements and their commercial formulations. From a manufacturing point of view, the production of such devices is less complex and thus lowers the investment and manufacturing cost. PMID:20490289

Phaeochromocytoma in pregnancy: safe vaginal delivery, is it possible?

PubMed

Kapoor, Garima; Salhan, Sudha; Sarda, Nivedita; Sarda, A K; Aggarwal, Deepika

2013-04-01

Pheochromocytoma in pregnancy is rare (1 in 50,000 full term pregnancies). Recognition of the condition is central to improving outcome (maternal and foetal mortality is reduced from 58% and 56%, respectively to 2% and 11-15%, respectively). An antenatal patient in third trimester diagnosed as pheochromocytoma has been described. Diagnosis of pheochromocytoma was confirmed by urinary VMA levels and demonstration of right adrenal mass on ultrasound. A multidisciplinary approach was used and the patient received antihypertensives for 10 days. Vaginal delivery was conducted under epidural analgesia and the patient was kept under close surveillance. She delivered a healthy baby girl weighing 2.5 kg. The intrapartum and the postpartum period were uneventful. Adrenalectomy was done at 6 weeks postpartum. Using multidisciplinary approach and individualised management decreases both maternal and foetal morbidity and mortality. Selected multigravidae cases and those with previous history of short uncomplicated labour, may be considered for vaginal delivery under epidural analgesia and with back up facilities available to manage hypertensive crisis.

Perineal Pain Management with Cryotherapy after Vaginal Delivery: A Randomized Clinical Trial.

PubMed

Morais, Ítalo; Lemos, Andréa; Katz, Leila; Melo, Lorena Fernandes Rosendo de; Maciel, Mariano Maia; Amorim, Melania Maria Ramos de

2016-07-01

Introduction Systematic reviews that evaluate the perineal cryotherapy to reduce pain in the vaginal postpartum are inconclusive. Purpose To evaluate clinical effectiveness of cryotherapy in the management of humanized postpartum perineal pain and vaginal edema. Methods A double-bind randomized controlled clinical trial (UTN number: U1111-1131-8433) was conducted in a hospital in Northeastern, Brazil. Women were included following humanized childbirth. All had vaginal deliveries of a single, full-term pregnancy with cephalic presentation. Exclusion criteria included previous perineal lesion, episiotomy during the current delivery, instrumental delivery, uterine curettage and postpartum hemorrhage. In the experimental group, an ice pack was applied six times on the perineum for 20 minutes, reducing the temperature between 10 and 15 ° C, then 60 minutes without exposure to cold. In the non-cryotherapy, a water bag unable to reduce the temperature to this extent was used, compliance with the same application protocol of the first group. Perineal temperature was monitored at zero, 10 and 20 minutes for application in both groups. Evaluations were made immediately before and after the applications and 24 hours after delivery spontaneous, to determine the association between variables. Results A total of 80 women were included in the study, 40 in each group. There was no significant difference in scores of perineal pain and edema between the groups with or without cryotherapy until 24 hours after childbirth. There was no difference between groups when accomplished repeated measures analysis over the 24 hours after delivery, considering the median perineal pain (p = 0.3) and edema (p = 0.9). Perineal cryotherapy did not influence the amount of analgesics used (p = 0.07) and no adverse effect was registered. Conclusion The use of cryotherapy following normal vaginal delivery within the concept of humanized minimally interventionist childbirth had no

Vaginal delivery to reduce the risk of hypothermia to newborn

NASA Astrophysics Data System (ADS)

Zulala, Nuli Nuryanti; Sitaresmi, Mei Neni; Sulistyaningsih

2017-08-01

The prevalence of hypothermia in the world is in the range of 8.5% to 52%, while in Indonesia it is around 47%. Hypothermia has caused 6.3% of neonatal deaths. The method in the process of giving birth determines the way to take care of the newborn. This study aims to observe the effect of the method of delivery on the hypothermia in newborn. This research has obtained an approval from the Ethics Committee of Aisyiyah University, Yogyakarta. This prospective cohort study was conducted to 74 newborns in November 2016. The research subjects were divided into the group of Caesarian section (n = 28) and the group of vaginal delivery (n = 46). Axillary temperature was measured using a digital thermometer at 1st minute, 30th minute, 60th minute, 6th hour, 12th hour and 24th hour. The average temperature difference between the caesarian section group and vaginal delivery group at the 1st minute was at 36°C vs. 36.4° C, at 30th minute at 35.7°C vs. 36.5°C, at 60th minute at 36°C vs. 36.5°C), at 6th hour at 36.2 °C vs. 36.6°C), 12th hour at 36.4°C vs. 36.7°C, and at 24th hour at 36.7°C vs. 36.8°C. The results of the study showed that vaginal delivery could reduce the risk of hypothermia by 1.5 times compared to caesarian section (ρ-value 0.004 CI 95% 1.154 to 1.880)

Spontaneous Caecal Perforation Associated with Ogilvie’s Syndrome Following Vaginal Delivery – A Case Report

PubMed Central

VK, Sundeep; Kola, Sivasai Krishnaprasad; KG, Dharma Kumar

2014-01-01

Acute pseudo-obstruction of the large bowel, Ogilvie’s syndrome, can occur in the postpartum period following caesarean section which can result in caecal dilatation and may progress to perforation. This is quiet rare following normal vaginal delivery. Only two previous reports have been found in the English literature. We report a case of Ogilvie’s syndrome with caecal perforation following normal vaginal delivery. PMID:25121027

An inflatable ergonomic 3-chamber fundal pressure belt to assist vaginal delivery.

PubMed

Acanfora, Luisa; Rampon, Michela; Filippeschi, Marco; Marchi, Marco; Montisci, Massimo; Viel, Guido; Cosmi, Erich

2013-01-01

To evaluate whether Baby-guard-a new medical device with an ergonomic 3-chamber inflatable abdominal belt-can reduce complications associated with vaginal delivery. A randomized controlled single-blind prospective study of 80 pregnant women delivering at term was conducted at San Giuseppe Hospital, Empoli, Italy. In the study group (n=40), the abdominal belt was inflated to optimal therapeutic pressures. In the control group (n=40), the abdominal belt was inflated to minimal, non-therapeutic pressures. Factors relating to maternal, fetal, and labor complications during vaginal delivery were evaluated. Compared with the control group, women in the study group experienced a lower incidence of perineal and cervical lacerations (P<0.001); reduced use of the Kristeller maneuver (P<0.001); shorter duration of the second stage of labor (P<0.001); less psychologic and physical fatigue (P<0.001); fewer maternal requests for cesarean delivery during labor (P<0.001); fewer vacuum extractions (P<0.01); and fewer cesarean deliveries (P<0.02). No neonatal intensive care unit admissions were recorded in the study group versus 7 in the control group (P<0.012). Use of the ergonomic 3-chamber inflatable abdominal belt system reduced the incidence of risks associated with vaginal labor. Clinical trials.gov identifier: NCT01566331. Copyright © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Does meperidine analgesia affect the incidence of obstetric lacerations at vaginal delivery?

PubMed

Mizrachi, Yossi; Leytes, Sophia; Levy, Michal; Ginath, Shimon; Bar, Jacob; Ezri, Tiberiu; Kovo, Michal

2018-03-01

To study whether meperidine analgesia affects the incidence of obstetric lacerations at normal vaginal deliveries. A retrospective cohort study of all women with term vertex singleton pregnancies, who underwent normal vaginal deliveries, in a single tertiary hospital, between 2011 and 2015, was performed. The incidence of various obstetric lacerations was compared between deliveries with meperidine analgesia and deliveries with no analgesia. Deliveries with epidural analgesia and instrumental deliveries were excluded. An intravenous infusion of 75 mg of meperidine was administered together with 25 mg of promethazine. A multivariate logistic regression analysis was performed to assess the association between meperidine analgesia and obstetric lacerations, after controlling for confounders. Overall, 5227 (91.8%) deliveries with no analgesia and 466 (8.1%) deliveries with meperidine analgesia were included. Meperidine analgesia was associated with a decreased risk of first- and second-degree perineal lacerations (adjusted OR = 0.63, 95% CI = 0.49-0.81), and a decreased risk of any suturing (adjusted OR = 0.73, 95% CI = 0.59-0.91), after controlling for confounders. Meperidine analgesia did not affect the risk of severe perineal lacerations or episiotomies. Meperidine analgesia may have a protective effect against first- and second-degree perineal lacerations.

Development of a liposome microbicide formulation for vaginal delivery of octylglycerol for HIV prevention

PubMed Central

Wang, Lin; Sassi, Alexandra Beumer; Patton, Dorothy; Isaacs, Charles; Moncla, B. J.; Gupta, Phalguni; Rohan, Lisa Cencia

2015-01-01

The feasibility of using a liposome drug delivery system to formulate octylglycerol (OG) as a vaginal microbicide product was explored. A liposome formulation was developed containing 1% OG and phosphatidyl choline in a ratio that demonstrated in vitro activity against Neisseria gonorrhoeae, HSV-1, HSV-2 and HIV-1 while sparing the innate vaginal flora, Lactobacillus. Two conventional gel formulations were prepared for comparison. The OG liposome formulation with the appropriate OG/lipid ratio and dosing level had greater efficacy than either conventional gel formulation and maintained this efficacy for at least 2 months. No toxicity was observed for the liposome formulation in ex vivo testing in a human ectocervical tissue model or in vivo testing in the macaque safety model. Furthermore, minimal toxicity was observed to lactobacilli in vitro or in vivo safety testing. The OG liposome formulation offers a promising microbicide product with efficacy against HSV, HIV and N. gonorrhoeae. PMID:22149387

Use of lubricant gel to shorten the second stage of labor during vaginal delivery.

PubMed

Aquino, Carmen Imma; Saccone, Gabriele; Troisi, Jacopo; Zullo, Fulvio; Guida, Maurizio; Berghella, Vincenzo

2018-05-27

Vaginal application of lubricant during labor has been studied to shorten the length of the second stage of labor. To evaluate whether vaginal application of lubricant shortens the second stage of labor. Electronic databases were searched from their inception until February 2018. No restrictions for language or geographic location were applied. Randomized controlled trials (RCTs) comparing the use of lubricant of the vaginal canal (ie intervention group) with a control group (ie no lubricant) in pregnant women with singleton gestation and cephalic presentation undergoing spontaneous vaginal delivery at term. Trials on other interventions that might impact second stage of labor (pushing methods, perineal massage, Ritgen's maneuver, etc.) were not included. All analyses were done using an intention-to-treat approach. The primary outcome was the length of the second stage of labor. Pooled analysis was performed using the random-effects model of DerSimonian and Laird to produce summary treatment effects in terms of mean difference (MD) with 95% confidence interval (CI). Three RCTs including 512 women evaluating the effect of lubricant application during labor were included in the meta-analysis. All trials included pregnant women with singleton gestations in cephalic presentation at term undergoing spontaneous vaginal delivery. One trial included only nulliparous women, while the other two included both nulliparous and multiparous women. Lubricant application started in the first stage before the active phase of labor, and was done intermittently by the midwife or the physician. A sterile gel was applied into the vaginal canal manually or with an applicator. All trials used water-soluble gel. The quantity of gel used was about 2-5 ml for each vaginal examination. There were no statistically significant differences, comparing women who received lubricant gel during labor with those who did not, in the lengths of second stage of labor (MD -7.11 minutes, 95% CI -15

Vaginal delivery after previous caesarean section: is X-ray pelvimetry necessary?

PubMed

Thubisi, M; Ebrahim, A; Moodley, J; Shweni, P M

1993-05-01

To determine whether antepartum X-ray pelvimetry (XRP) reliably identified women suitable for a trial labour or repeat elective caesarean section after one previous section. A prospective controlled trial in which women were randomly allocated to either an antepartum XRP group who had XRP at 36 weeks gestation to determine mode of delivery, or a control group who had a trial labour without antepartum XRP. Following delivery, all controls had postpartum XRP. Department of Obstetrics and Gynaecology, King Edward VIII Hospital, Durban, South Africa. Three hundred-six women with a history of one previous caesarean section. Mode of delivery, birthweight and maternal and perinatal mortality and morbidity in the two groups. In the antepartum XRP group, 23 of 144 (16%) of women delivered vaginally compared with 60 of 144 (42%) controls (P < 0.0001). Of the 84 women with adequate antepartum XRP only 23 (27.7%) delivered vaginally. In the control group, 33 of 60 (55%) women who had vaginal deliveries had inadequate postpartum XRP and would have had a caesarean section if this information was known in the antepartum period; 62 of 84 (74%) caesarean sections in the control group had adequate postpartum XRP. Birthweight of the infants was similar in the two groups. There were no maternal or perinatal deaths. Maternal morbidity was similar in the two groups. Neonatal morbidity was minimal. Antepartum XRP is not necessary prior to a trial labour in women with one previous caesarean section. It increases the caesarean section rate and is a poor predictor of the outcome of labour.

Anal sphincter injury in vaginal deliveries complicated by shoulder dystocia.

PubMed

Hehir, Mark P; Rubeo, Zachary; Flood, Karen; Mardy, Anne H; O'Herlihy, Colm; Boylan, Peter C; D'Alton, Mary E

2018-03-01

Shoulder dystocia is an obstetric emergency that occurs in 0.2-3% of all cephalic vaginal deliveries. We hypothesized that because of the difficult nature of deliveries complicated by shoulder dystocia, the condition may be associated with anal sphincter injury. We sought to identify risk factors for obstetric anal sphincter injury in women with shoulder dystocia. This retrospective analysis included all cases of shoulder dystocia from 2007 to 2011 at two large tertiary referral centers, in the USA and Ireland. Details of maternal demographics, intrapartum characteristics, and delivery outcomes in cases of shoulder dystocia were analyzed. Univariate and multivariate analyses were used to describe the association between shoulder dystocia and anal sphincter injury. There were 685 cases of shoulder dystocia, and the rate of shoulder dystocia was similar at both institutions. The incidence of anal sphincter injury was 8.8% (60 out of 685). The rate was 14% (45 out of 324) in nulliparas and 4.2% (15 out of 361) in multiparas. Women with sphincter injury were more likely to be nulliparous (75% [45 out of 60] vs 45% [279 out of 625]; p < 0.0001), have had an operative vaginal delivery (50% [30 out of 60] vs 36% [226 out of 625]; p = 0.03) and require internal maneuvers (50% [30 out of 60] vs 32% [198 out of 625], p = 0.004) than those with an intact sphincter. On multivariate regression analysis, these predictors of sphincter injury remained significant when adjusted for other risk factors. Episiotomy was negatively associated with sphincter injury on multivariate regression analysis. In a retrospective cohort of 685 women with shoulder dystocia, the risk of anal sphincter injury is 9%. Risk factors include nulliparity, operative vaginal delivery, and use of internal maneuvers, whereas episiotomy was found to have a protective effect against anal sphincter injury during cases of shoulder dystocia.

Neonatal outcome of very preterm twins: policy of planned vaginal or cesarean delivery.

PubMed

Sentilhes, Loïc; Oppenheimer, Anne; Bouhours, Anne-Charlotte; Normand, Estelle; Haddad, Bassam; Descamps, Philippe; Marpeau, Loïc; Goffinet, François; Kayem, Gilles

2015-07-01

The objective of the study was to compare neonatal mortality and morbidity in very preterm twins with the first twin in cephalic presentation in hospitals with a policy of planned vaginal delivery (PVD) and those with a policy of planned cesarean delivery (PCD). Women with preterm cephalic first twins delivered after preterm labor and/or premature preterm rupture of membranes from 26(0/7) to 31(6/7) weeks of gestation were identified from the databases of 6 perinatal centers and classified as PVD or PCD according to the center's management policy from 1999 to 2010. Severe neonatal morbidity was defined as any of the following: intraventricular hemorrhage grades 3-4, periventricular leukomalacia, necrotizing enterocolitis, bronchopulmonary dysplasia, and hospital death. The independent effect of the planned mode of delivery, defined by the center's management policy, was tested and quantified with a 2-level multivariable logistic regression. The PVD group included 248 women, and the PCD group 63. Maternal characteristics did not differ between the 2 groups. The rate of vaginal delivery was 85.9% (213 of 248) vs 20.6% (13 of 63) (P < .001), and the rate of cesarean delivery for the second twin was 1.6% (4 of 248) vs 4.8% (3 of 63) (P = .13) for PVD and PCD. PVD had no independent effect on either newborn hospital mortality or severe neonatal composite morbidity. A policy of planned vaginal delivery of very preterm twins with the first twin in cephalic presentation does not increase either severe neonatal morbidity or mortality. Copyright © 2015 Elsevier Inc. All rights reserved.

An overview of in vitro dissolution/release methods for novel mucosal drug delivery systems.

PubMed

Jug, Mario; Hafner, Anita; Lovrić, Jasmina; Kregar, Maja Lusina; Pepić, Ivan; Vanić, Željka; Cetina-Čižmek, Biserka; Filipović-Grčić, Jelena

2018-01-05

In vitro dissolution/release tests are an important tool in the drug product development phase as well as in its quality control and the regulatory approval process. Mucosal drug delivery systems are aimed to provide both local and systemic drug action via mucosal surfaces of the body and exhibit significant differences in formulation design, as well as in their physicochemical and release characteristics. Therefore it is not possible to devise a single test system which would be suitable for release testing of such complex dosage forms. This article is aimed to provide a comprehensive review of both compendial and noncompendial methods used for in vitro dissolution/release testing of novel mucosal drug delivery systems aimed for ocular, nasal, oromucosal, vaginal and rectal administration. Copyright © 2017 Elsevier B.V. All rights reserved.

New strategies for local treatment of vaginal infections.

PubMed

Palmeira-de-Oliveira, Rita; Palmeira-de-Oliveira, Ana; Martinez-de-Oliveira, José

2015-09-15

Vaginal infections are extremely prevalent, particularly among women of reproductive age. Although they do not result in high mortality rates, these infections are associated with high levels of anxiety and reduction of quality of life. In most cases, topical treatment of vaginal infections has been shown to be at least as effective as oral treatment, resulting in higher local drug concentrations, with fewer drug interactions and adverse effects. Furthermore, the emergence of microbial resistance to chemotherapeutics and the difficulties in managing infection recurrences sustain the need for more effective local treatments. However, conventional dosage forms have been associated with low retention in the vagina and discomfort. Formulation strategies such as the development of bioadhesive, thermogelling systems and microtechnological or nanotechnological approaches have been proposed to improve delivery of traditional drugs, and other treatment modalities such as new drugs, plant extracts, and probiotics are being studied. This article reviews the recent strategies studied to improve the treatment and prevention of the commonest vaginal infections-namely, vaginal bacteriosis, aerobic vaginitis, vulvovaginal candidosis, and trichomoniasis-through the intravaginal route. Copyright © 2015 Elsevier B.V. All rights reserved.

Postpartum surveillance of bacteriuria in term vaginal deliveries.

PubMed Central

Orrett, F. A.; Premanand, N.

1998-01-01

This study examined the prevalence of bacteriuria in early postpartum period after term vaginal delivery in Trinidad, West Indies. Asymptomatic bacteriuria occurred in 58 (34.5%) of 168 patients tested. The prevalence of bacteriuria was significantly higher in non-catheterized patients than in catheterized patients and occurred more commonly in patients who were 20 to 29 years old and who were primigravida rather than multigravida. Forty-four patients had a history of urinary tract infection; 18 (40.9%) of these patients had positive urine cultures. Although 10 patients had a vaginal discharge in the late third trimester, none presented with postpartum bacteriuria. Because of the high prevalence of postpartum bacteriuria and the potential to progress to pyelonephritis and chronic renal disease, quantitative urine cultures for all postnatal patients and curative treatment for all positive cultures are recommend. PMID:9549982

Severe perineal laceration during operative vaginal delivery: the impact of occiput posterior position.

PubMed

Hirsch, E; Elue, R; Wagner, A; Nelson, K; Silver, R K; Zhou, Y; Adams, M G

2014-12-01

To identify risk factors for severe (third/fourth degree) perineal laceration with operative vaginal delivery (OVD, forceps or vacuum). Case-control study comparing singleton OVDs with or without severe laceration (n=138). In multivariable analyses, severe perineal laceration was associated with occiput posterior (OP) position at delivery, vaginal nulliparity, use of forceps, longer period pushing in the second stage and lower gestational age, but not birth weight, labor induction or episiotomy. Among 29 OP patients at full dilation, 9/13 (69%) attempted rotations to occiput anterior (OA) were successful, and 14/16 (88%) patients in whom rotation was not attempted remained OP at delivery. Successful rotation from OP to OA was associated with fewer severe lacerations than no attempt or unsuccessful rotation (22 vs 75%, P=0.01). Severe perineal laceration during OVD is associated with OP position at delivery and is reduced threefold in patients successfully rotated from OP to OA.

Severe postpartum haemorrhage after vaginal delivery: a statistical process control chart to report seven years of continuous quality improvement.

PubMed

Dupont, Corinne; Occelli, Pauline; Deneux-Tharaux, Catherine; Touzet, Sandrine; Duclos, Antoine; Bouvier-Colle, Marie-Hélène; Rudigoz, René-Charles; Huissoud, Cyril

2014-07-01

Severe postpartum haemorrhage after vaginal delivery: a statistical process control chart to report seven years of continuous quality improvement To use statistical process control charts to describe trends in the prevalence of severe postpartum haemorrhage after vaginal delivery. This assessment was performed 7 years after we initiated a continuous quality improvement programme that began with regular criteria-based audits Observational descriptive study, in a French maternity unit in the Rhône-Alpes region. Quarterly clinical audit meetings to analyse all cases of severe postpartum haemorrhage after vaginal delivery and provide feedback on quality of care with statistical process control tools. The primary outcomes were the prevalence of severe PPH after vaginal delivery and its quarterly monitoring with a control chart. The secondary outcomes included the global quality of care for women with severe postpartum haemorrhage, including the performance rate of each recommended procedure. Differences in these variables between 2005 and 2012 were tested. From 2005 to 2012, the prevalence of severe postpartum haemorrhage declined significantly, from 1.2% to 0.6% of vaginal deliveries (p<0.001). Since 2010, the quarterly rate of severe PPH has not exceeded the upper control limits, that is, been out of statistical control. The proportion of cases that were managed consistently with the guidelines increased for all of their main components. Implementation of continuous quality improvement efforts began seven years ago and used, among other tools, statistical process control charts. During this period, the prevalence of severe postpartum haemorrhage after vaginal delivery has been reduced by 50%. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Durable protection from vaginal simian-human immunodeficiency virus infection in macaques by tenofovir gel and its relationship to drug levels in tissue.

PubMed

Dobard, Charles; Sharma, Sunita; Martin, Amy; Pau, Chou-Pong; Holder, Angela; Kuklenyik, Zsuzsanna; Lipscomb, Jonathan; Hanson, Debra L; Smith, James; Novembre, Francis J; García-Lerma, J Gerardo; Heneine, Walid

2012-01-01

A vaginal gel containing 1% tenofovir (TFV) was found to be safe and effective in reducing HIV infection in women when used pericoitally. Because of the long intracellular half-life of TFV and high drug exposure in vaginal tissues, we hypothesized that a vaginal gel containing TFV may provide long-lasting protection. Here, we performed delayed-challenge experiments and showed that vaginal 1% TFV gel protected 4/6 macaques against vaginal simian-human immunodeficiency virus (SHIV) exposures occurring 3 days after gel application, demonstrating long-lasting protection. Despite continued gel dosing postinfection, neither breakthrough infection had evidence of drug resistance by ultrasensitive testing of SHIV in plasma and vaginal lavage. Analysis of the active intracellular tenofovir diphosphate (TFV-DP) in vaginal lymphocytes collected 4 h to 3 days after gel dosing persistently showed high TFV-DP levels (median, 1,810 fmol/10(6) cells) between 4 and 24 h that exceed the 95% inhibitory concentration (IC(95)), reflecting rapid accumulation and long persistence. In contrast to those in peripheral blood mononuclear cells (PBMCs) following oral dosing, TFV-DP levels in vaginal lymphocytes decreased approximately 7-fold by 3 days, exhibiting a much higher rate of decay. We observed a strong correlation between intracellular TFV-DP in vaginal lymphocytes, in vitro antiviral activity, and in vivo protection, suggesting that TFV-DP above the in vitro IC(95) in vaginal lymphocytes is a good predictor of high efficacy. Data from this model reveal an extended window of protection by TFV gel that supports coitus-independent use. The identification of protective TFV-DP concentrations in vaginal lymphocytes may facilitate the evaluation of improved delivery methods of topical TFV and inform clinical studies.

[Operative vaginal deliveries training].

PubMed

Dupuis, O

2008-12-01

The appropriate use of forceps, vacuums or spatulas facilitates the rapid delivery of foetuses faced with life-threatening situations. It also makes possible the relief of certain cases of prolonged second-stage labor. In France, operative vaginal delivery (OVD) accounts for approximately 10% of all births. OVD training aims to optimize maternal, as well as neonatal safety. It should enable trainees to indicate or contraindicate an OVD safely, as well as to choose the appropriate instrument, use it correctly, and master quality control principles. Traditional OVD training is confronted with both spatial and time-related limitations. Spatial constraints involve both the teacher and trainee who only have limited visual access to the pelvic canal, and the head of the foetus; the time constraint occurs whenever the OVD occurs in an emergency setting. These limitations have been further aggravated by new constraints: decreasing time dedicated to training (European safety rules prohibit work the day after night duty), increasing litigation, and constraints imposed by society. Training by means of simulation removes such limitations making it possible to both avoid exposing pregnant women to the hazards of traditional training, and adapt the training to the skills of each trainee. OVD training should include forceps, vacuums and the use of spatulas. The OVD skills of obstetricians should be audited regularly on both a personal and a confidential level. Such audits could be based on a method using a simulator. Prospective studies comparing traditional and simulation-based training should be encouraged.

Buccal drug delivery.

PubMed

Smart, John D

2005-05-01

Buccal formulations have been developed to allow prolonged localised therapy and enhanced systemic delivery. The buccal mucosa, however, while avoiding first-pass effects, is a formidable barrier to drug absorption, especially for biopharmaceutical products (proteins and oligonucleotides) arising from the recent advances in genomics and proteomics. The buccal route is typically used for extended drug delivery, so formulations that can be attached to the buccal mucosa are favoured. The bioadhesive polymers used in buccal drug delivery to retain a formulation are typically hydrophilic macro-molecules containing numerous hydrogen bonding groups. Newer second-generation bioadhesives have been developed and these include modified or new polymers that allow enhanced adhesion and/or drug delivery, in addition to site-specific ligands such as lectins. Over the last 20 years a wide range of formulations has been developed for buccal drug delivery (tablet, patch, liquids and semisolids) but comparatively few have found their way onto the market. Currently, this route is restricted to the delivery of a limited number of small lipophilic molecules that readily cross the buccal mucosa. However, this route could become a significant means for the delivery of a range of active agents in the coming years, if the barriers to buccal drug delivery are overcome. In particular, patient acceptability and the successful systemic delivery of large molecules (proteins, oligonucleotides and polysaccharides) via this route remains both a significant opportunity and challenge, and new/improved technologies may be required to address these.

A Rare Case: Rupture of Internal Pudendal and Uterine Artery in a Vaginal Delivery.

PubMed

Chughtai, Novera G; Rizvi, Raheela Mohsin

2018-03-01

The management of puerperal hematomas after normal delivery has always been challenging for obstetricians. Vulvar, vulvovaginal, or paravaginal hematomas are common. On the other hand, retroperitoneal hematomas are uncommon and can be life-threatening. The diagnosis of vascular injury is rarely made preoperatively as atonic or traumatic postpartum hemorrhage (PPH), uterine rupture and amniotic fluid embolism are more common differential diagnoses. Injury to internal pudendal and uterine vessels is extremely rare in cases of vaginal delivery and, therefore, the literature on this topic is very scarce. We present a rare case of both internal pudendal and uterine artery rupture in a normal vaginal delivery, which led to massive postpartum hemorrhage. The diagnosis was made on Magnetic Resonance imaging (MRI) and arterial embolization was performed. This case stresses on the need for careful post-delivery monitoring for revealed postpartum hemorrhage. Vascular injury is a rare life-threatening cause of obstetric shock, and active; and timely operative intervention can prevent morbidity and mortality.

Prevalence and predictors of urinary/anal incontinence after vaginal delivery: prospective study of Nigerian women.

PubMed

Obioha, Kingsley Chukwu; Ugwu, Emmanuel Onyebuchi; Obi, Samuel Nnamdi; Dim, Cyril Chukwudi; Oguanuo, Theophilus Chimezie

2015-09-01

Urinary and anal incontinence are major public health problems impacting on the quality of life of affected women, with resultant loss of self-esteem. Despite the anticipated magnitude of this public health problem in sub-Saharan Africa, there is paucity of data on the prevalence of urinary and/or anal incontinence after childbirth in the region. This study determined the prevalence and predictors of urinary and anal incontinence after vaginal delivery among women in Enugu, southeastern Nigeria. This was a longitudinal study of 230 consecutive parturients at the University of Nigeria Teaching Hospital, Enugu, Nigeria. Eligible women were followed up immediately, 6 weeks, and 3 months postpartum to assess the development of urinary and/or anal incontinence using validated questionnaires. Overall, 28 women had urinary incontinence, giving a cumulative prevalence rate of 12.2 %. The cumulative prevalence rate was 13.5 % for anal incontinence and 3 % for combined urinary and anal incontinence. Age, social class, parity, prolonged second stage of labor, and neonatal birth weight were significantly associated with postpartum urinary incontinence (P < 0.05). On the other hand, age, parity, prolonged second stage of labor, episiotomy, and instrumental vaginal delivery were significantly associated with postpartum anal incontinence (P < 0.05). Urinary and anal incontinence are common after vaginal delivery in Enugu, Nigeria. Modification of obstetric care and discouraging preventable predisposing factors for incontinence, such as prolonged second stage of labor and vaginal delivery of macrosomic babies, are measures that may reduce the prevalence of postpartum incontinence in our population.

Cell-Mediated Drugs Delivery

PubMed Central

Batrakova, Elena V.; Gendelman, Howard E.; Kabanov, Alexander V.

2011-01-01

INTRODUCTION Drug targeting to sites of tissue injury, tumor or infection with limited toxicity is the goal for successful pharmaceutics. Immunocytes (including mononuclear phagocytes (dendritic cells, monocytes and macrophages), neutrophils, and lymphocytes) are highly mobile; they can migrate across impermeable barriers and release their drug cargo at sites of infection or tissue injury. Thus immune cells can be exploited as trojan horses for drug delivery. AREAS COVERED IN THIS REVIEW This paper reviews how immunocytes laden with drugs can cross the blood brain or blood tumor barriers, to facilitate treatments for infectious diseases, injury, cancer, or inflammatory diseases. The promises and perils of cell-mediated drug delivery are reviewed, with examples of how immunocytes can be harnessed to improve therapeutic end points. EXPERT OPINION Using cells as delivery vehicles enables targeted drug transport, and prolonged circulation times, along with reductions in cell and tissue toxicities. Such systems for drug carriage and targeted release represent a novel disease combating strategy being applied to a spectrum of human disorders. The design of nanocarriers for cell-mediated drug delivery may differ from those used for conventional drug delivery systems; nevertheless, engaging different defense mechanisms into drug delivery may open new perspectives for the active delivery of drugs. PMID:21348773

Controlled Drug Delivery Using Microdevices

PubMed Central

Sanjay, Sharma T.; Dou, Maowei; Fu, Guanglei; Xu, Feng; Li, XiuJun

2016-01-01

Therapeutic drugs administered systematically are evenly distributed to the whole body through blood circulation and have to cross many biological barriers before reaching the pathological site. Conventional drug delivery may make drugs inactive or reduce their potency as they may be hydrolyzed or degraded enzymatically and are rapidly excreted through the urinary system resulting in suboptimal concentration of drugs at the desired site. Controlled drug delivery aims to localize the pharmacological activity of the drug to the desired site at desired release rates. The advances made by micro/nanofluidic technologies have provided new opportunities for better-controlled drug delivery. Various components of a drug delivery system can be integrated within a single tiny micro/nanofluidic chip. This article reviews recent advances of controlled drug delivery made by microfluidic/nanofluidic technologies. We first discuss microreservoir-based drug delivery systems. Then we highlight different kinds of microneedles used for controlled drug delivery, followed with a brief discussion about the current limitations and the future prospects of controlled drug delivery systems. PMID:26813304

Controlled Drug Delivery Using Microdevices.

PubMed

Sanjay, Sharma T; Dou, Maowei; Fu, Guanglei; Xu, Feng; Li, XiuJun

Therapeutic drugs administered systematically are evenly distributed to the whole body through blood circulation and have to cross many biological barriers before reaching the pathological site. Conventional drug delivery may make drugs inactive or reduce their potency as they may be hydrolyzed or degraded enzymatically and are rapidly excreted through the urinary system resulting in suboptimal concentration of drugs at the desired site. Controlled drug delivery aims to localize the pharmacological activity of the drug to the desired site at desired release rates. The advances made by micro/nanofluidic technologies have provided new opportunities for better-controlled drug delivery. Various components of a drug delivery system can be integrated within a single tiny micro/nanofluidic chip. This article reviews recent advances of controlled drug delivery made by microfluidic/nanofluidic technologies. We first discuss microreservoir-based drug delivery systems. Then we highlight different kinds of microneedles used for controlled drug delivery, followed with a brief discussion about the current limitations and the future prospects of controlled drug delivery systems.

MRI in ocular drug delivery

PubMed Central

Li, S. Kevin; Lizak, Martin J.; Jeong, Eun-Kee

2008-01-01

Conventional pharmacokinetic methods for studying ocular drug delivery are invasive and cannot be conveniently applied to humans. The advancement of MRI technology has provided new opportunities in ocular drug-delivery research. MRI provides a means to non-invasively and continuously monitor ocular drug-delivery systems with a contrast agent or compound labeled with a contrast agent. It is a useful technique in pharmacokinetic studies, evaluation of drug-delivery methods, and drug-delivery device testing. Although the current status of the technology presents some major challenges to pharmaceutical research using MRI, it has a lot of potential. In the past decade, MRI has been used to examine ocular drug delivery via the subconjunctival route, intravitreal injection, intrascleral injection to the suprachoroidal space, episcleral and intravitreal implants, periocular injections, and ocular iontophoresis. In this review, the advantages and limitations of MRI in the study of ocular drug delivery are discussed. Different MR contrast agents and MRI techniques for ocular drug-delivery research are compared. Ocular drug-delivery studies using MRI are reviewed. PMID:18186077

Do changes in anal sphincter anatomy correlate with anal function in women with a history of vaginal delivery?

PubMed

Murad-Regadas, Sthela Maria; Dealcanfreitas, Iris Daiana; Regadas, Francisco Sergio Pinheiro; Rodrigues, Lusmar Veras; Fernandes, Graziela Olivia da Silva; Pereira, Jacyara de Jesus Rosa

2014-01-01

To evaluate anal sphincter anatomy using three-dimensional ultrasonography (3-DAUS) in incontinent women with vaginal delivery, correlate anatomical findings with symptoms of fecal incontinence and determine the effect of vaginal delivery on anal canal anatomy and function. Female with fecal incontinence and vaginal delivery were assessed with Wexner's score, manometry, and 3DAUS. A control group comprising asymptomatic nulliparous was included. Anal pressure, the angle of the defect and length of the external anal sphincter (EAS), the anterior and posterior internal anal sphincter (IAS), the EAS + puborectal and the gap were measured and correlated with score. Of the 62, 49 had fecal incontinence and 13 were asymptomatic. Twenty five had EAS defects, 8 had combined EAS+IAS defects, 16 had intact sphincters and continence scores were similar. Subjects with sphincter defects had a shorter anterior EAS, IAS and longer gap than women without defects. Those with a vaginal delivery and intact sphincters had a shorter anterior EAS and longer gap than nulliparous. We found correlations between resting pressure and anterior EAS and IAS length in patients with defects. Fecal incontinence symptoms did not correlate with anal pressures and anal sphincter anatomy changes, but women with sphincter defects have shorter anterior EAS and IAS and a longer gap.

Self-testing of vaginal pH to prevent preterm delivery: a controlled trial.

PubMed

Bitzer, Eva-Maria; Schneider, Andrea; Wenzlaff, Paul; Hoyme, Udo B; Siegmund-Schultze, Elisabeth

2011-02-01

From 2004 to 2006, in a model project carried out by four German health insurers, expectant mothers were offered self-testing of vaginal pH in order to prevent preterm delivery. They were given pH test gloves on request so that they could measure their vaginal pH twice a week from the 12(th) to the 32(nd) week of gestation. They were instructed to consult with a gynecologist after any positive result. All further diagnostic or therapeutic decisions were at the discretion of the treating gynecologist. We assessed the effectiveness of the screening intervention, using delivery before the 37th week of gestation as the primary endpoint. In this prospective, controlled trial, we collected data on deliveries from 2004 to 2006 that were covered by the four participating insurers in five German federal states. We compared the outcomes of pregnancy in women who did and did not request test gloves (intervention group, [IG], and control group, [CG]). The data were derived from claims data of the participating insurers, as well as from a nationwide quality assurance auditing program for obstetrics and perinatal care. Propensity score matching and multivariate adjustment were used to control for the expected self-selection bias. The study sample comprised 149 082 deliveries. 13% of the expectant mothers requested test gloves, about half of them up to the 16(th) week of gestation. As expected, women with an elevated risk of preterm birth requested test gloves more often. Delivery before the 37(th) week of gestation was slightly more common in the intervention group than in the control group (IG 7.97%, CG 7.52%, relative risk 1.06, 95% confidence interval 1.00-1.12). This result was of borderline statistical significance in the propensity score matched analysis, but it was not statistically significant in the multivariate model. This trial did not demonstrate the efficacy of self-testing of vaginal pH for the prevention of preterm delivery (< 37 weeks of gestation).

Peptide and protein delivery using new drug delivery systems.

PubMed

Jain, Ashish; Jain, Aviral; Gulbake, Arvind; Shilpi, Satish; Hurkat, Pooja; Jain, Sanjay K

2013-01-01

Pharmaceutical and biotechnological research sorts protein drug delivery systems by importance based on their various therapeutic applications. The effective and potent action of the proteins/peptides makes them the drugs of choice for the treatment of numerous diseases. Major research issues in protein delivery include the stabilization of proteins in delivery devices and the design of appropriate target-specific protein carriers. Many efforts have been made for effective delivery of proteins/peptidal drugs through various routes of administrations for successful therapeutic effects. Nanoparticles made of biodegradable polymers such as poly lactic acid, polycaprolactone, poly(lactic-co-glycolic acid), the poly(fumaric-co-sebacic) anhydride chitosan, and modified chitosan, as well as solid lipids, have shown great potential in the delivery of proteins/peptidal drugs. Moreover, scientists also have used liposomes, PEGylated liposomes, niosomes, and aquasomes, among others, for peptidal drug delivery. They also have developed hydrogels and transdermal drug delivery systems for peptidal drug delivery. A receptor-mediated delivery system is another attractive strategy to overcome the limitation in drug absorption that enables the transcytosis of the protein across the epithelial barrier. Modification such as PEGnology is applied to various proteins and peptides of the desired protein and peptides also increases the circulating life, solubility and stability, pharmacokinetic properties, and antigenicity of protein. This review focuses on various approaches for effective protein/peptidal drug delivery, with special emphasis on insulin delivery.

Polymeric nanoparticles affect the intracellular delivery, antiretroviral activity and cytotoxicity of the microbicide drug candidate dapivirine.

PubMed

das Neves, José; Michiels, Johan; Ariën, Kevin K; Vanham, Guido; Amiji, Mansoor; Bahia, Maria Fernanda; Sarmento, Bruno

2012-06-01

To assess the intracellular delivery, antiretroviral activity and cytotoxicity of poly(ε-caprolactone) (PCL) nanoparticles containing the antiretroviral drug dapivirine. Dapivirine-loaded nanoparticles with different surface properties were produced using three surface modifiers: poloxamer 338 NF (PEO), sodium lauryl sulfate (SLS) and cetyl trimethylammonium bromide (CTAB). The ability of nanoparticles to promote intracellular drug delivery was assessed in different cell types relevant for vaginal HIV transmission/microbicide development. Also, antiretroviral activity of nanoparticles was determined in different cell models, as well as their cytotoxicity. Dapivirine-loaded nanoparticles were readily taken up by different cells, with particular kinetics depending on the cell type and nanoparticles, resulting in enhanced intracellular drug delivery in phagocytic cells. Different nanoparticles showed similar or improved antiviral activity compared to free drug. There was a correlation between increased antiviral activity and increased intracellular drug delivery, particularly when cell models were submitted to a single initial short-course treatment. PEO-PCL and SLS-PCL nanoparticles consistently showed higher selectivity index values than free drug, contrasting with high cytotoxicity of CTAB-PCL. These results provide evidence on the potential of PCL nanoparticles to affect in vitro toxicity and activity of dapivirine, depending on surface engineering. Thus, this formulation approach may be a promising strategy for the development of next generation microbicides.

Impact of pregnancy and vaginal delivery on the passive and active mechanics of the rat vagina.

PubMed

Feola, Andrew; Moalli, Pamela; Alperin, Marianna; Duerr, Robbie; Gandley, Robin E; Abramowitch, Steven

2011-01-01

Remodeling of vaginal extracellular matrix and smooth muscle likely plays a critical role in reducing the risk of maternal injury during vaginal delivery by altering the mechanical properties to increase distension and reduce stress. Long-Evans rats were divided into five groups to examine the passive mechanical and active contractile properties throughout pregnancy and postpartum: virgin (n=17), mid-pregnant (Day 14-16, n=12), late-pregnant (Day 20-22, n=14), immediate postpartum (0-2 h after delivery, n=14), and 4 week postpartum (n=15). Longitudinal sections of vaginal tissue were loaded to failure uniaxially for passive mechanical or active contractile properties were examined. For passive mechanics, the tangent modulus decreased 45% by mid-pregnancy and immediately postpartum (p<0.001). The ultimate strain continuously increased up to 43% higher than virgin animals (p=0.007) in the immediate postpartum group. For active mechanics, the maximal contractile force was 36-56% lower through immediate postpartum animals, and was significantly more sensitive to K+ throughout pregnancy and postpartum (p=0.003). The changes observed in the passive and active properties of the rat vagina are consistent with what would be expected from a tissue that is remodeling to maximize its ability to distend at the time of vaginal delivery to facilitate passage of the fetus with minimal injury.

Predicting the chance of vaginal delivery after one cesarean section: validation and elaboration of a published prediction model.

PubMed

Fagerberg, Marie C; Maršál, Karel; Källén, Karin

2015-05-01

We aimed to validate a widely used US prediction model for vaginal birth after cesarean (Grobman et al. [8]) and modify it to suit Swedish conditions. Women having experienced one cesarean section and at least one subsequent delivery (n=49,472) in the Swedish Medical Birth Registry 1992-2011 were randomly divided into two data sets. In the development data set, variables associated with successful trial of labor were identified using multiple logistic regression. The predictive ability of the estimates previously published by Grobman et al., and of our modified and new estimates, respectively, was then evaluated using the validation data set. The accuracy of the models for prediction of vaginal birth after cesarean was measured by area under the receiver operating characteristics curve. For maternal age, body mass index, prior vaginal delivery, and prior labor arrest, the odds ratio estimates for vaginal birth after cesarean were similar to those previously published. The prediction accuracy increased when information on indication for the previous cesarean section was added (from area under the receiver operating characteristics curve=0.69-0.71), and increased further when maternal height and delivery unit cesarean section rates were included (area under the receiver operating characteristics curve=0.74). The correlation between the individual predicted vaginal birth after cesarean probability and the observed trial of labor success rate was high in all the respective predicted probability decentiles. Customization of prediction models for vaginal birth after cesarean is of considerable value. Choosing relevant indicators for a Swedish setting made it possible to achieve excellent prediction accuracy for success in trial of labor after cesarean. During the delicate process of counseling about preferred delivery mode after one cesarean section, considering the results of our study may facilitate the choice between a trial of labor or an elective repeat cesarean

Nanostructure-mediated drug delivery.

PubMed

Hughes, Gareth A

2005-03-01

Nanotechnology is expected to have an impact on all industries including semiconductors, manufacturing, and biotechnology. Tools that provide the capability to characterize and manipulate materials at the nanoscale level further elucidate nanoscale phenomena and equip researchers and developers with the ability to fabricate novel materials and structures. One of the most promising societal impacts of nanotechnology is in the area of nanomedicine. Personalized health care, rational drug design, and targeted drug delivery are some of the benefits of a nanomedicine-based approach to therapy. This review will focus on the development of nanoscale drug delivery mechanisms. Nanostructured drug carriers allow for the delivery of not only small-molecule drugs but also the delivery of nucleic acids and proteins. Delivery of these molecules to specific areas within the body can be achieved, which will reduce systemic side effects and allow for more efficient use of the drug.

Fungal diseases: could nanostructured drug delivery systems be a novel paradigm for therapy?

PubMed Central

Voltan, Aline Raquel; Quindós, Guillermo; Alarcón, Kaila P Medina; Fusco-Almeida, Ana Marisa; Mendes-Giannini, Maria José Soares; Chorilli, Marlus

2016-01-01

Invasive mycoses are a major problem for immunocompromised individuals and patients in intensive care units. Morbidity and mortality rates of these infections are high because of late diagnosis and delayed treatment. Moreover, the number of available antifungal agents is low, and there are problems with toxicity and resistance. Alternatives for treating invasive fungal infections are necessary. Nanostructured systems could be excellent carriers for antifungal drugs, reducing toxicity and targeting their action. The use of nanostructured systems for antifungal therapy began in the 1990s, with the appearance of lipid formulations of amphotericin B. This review encompasses different antifungal drug delivery systems, such as liposomes, carriers based on solid lipids and nanostructure lipids, polymeric nanoparticles, dendrimers, and others. All these delivery systems have advantages and disadvantages. Main advantages are the improvement in the antifungal properties, such as bioavailability, reduction in toxicity, and target tissue, which facilitates innovative therapeutic techniques. Conversely, a major disadvantage is the high cost of production. In the near future, the use of nanosystems for drug delivery strategies can be used for delivering peptides, including mucoadhesive systems for the treatment of oral and vaginal candidiasis. PMID:27540288

Comparable risk of childhood asthma after vaginal delivery and emergency caesarean section.

PubMed

Brix, Nis; Stokholm, Lonny; Jonsdottir, Fjola; Kristensen, Kim; Secher, Niels Jørgen

2017-01-01

Caesarean section is thought to be a risk factor for childhood asthma, but this association may be caused by confounding from, for instance, familial factors. To address this problem, we used twin pairs to assess the risk of childhood asthma after emergency caesarean section. The study was a register-based nation-wide matched cohort study using twin pairs to minimise residual confounding. Included were twin pairs in which the first twin was delivered vaginally and the second by emergency caesarean section during the study period from January 1997 through December 2012. In total, 464 twin pairs (928 twins) were included. In 30 pairs, the first twin (vaginal delivery) was diagnosed with asthma, but the second twin (emergency caesarean section) was not. In 20 pairs, the second twin (emergency caesarean section) was diagnosed with asthma, but the first twin (vaginal delivery) was not. In 11 pairs, both twins developed asthma. In the unadjusted analysis, emergency caesarean section did not affect the risk of asthma (odds ratio = 0.67 (95% confidence interval: 0.38-1.17); p = 0.16). After adjusting for birth weight, gender, umbilical cord pH, Apgar score at 5 min. and neonatal respiratory morbidity, the risk of childhood asthma following emergency caesarean section remained unchanged. Emergency caesarean section was not associated with childhood asthma. none. not relevant.

Characterization of particulate drug delivery systems for oral delivery of Peptide and protein drugs.

PubMed

Christophersen, Philip Carsten; Fano, Mathias; Saaby, Lasse; Yang, Mingshi; Nielsen, Hanne Mørck; Mu, Huiling

2015-01-01

Oral drug delivery is a preferred route because of good patient compliance. However, most peptide/ protein drugs are delivered via parenteral routes because of the absorption barriers in the gastrointestinal (GI) tract such as enzymatic degradation by proteases and low permeability acrossthe biological membranes. To overcome these barriers, different formulation strategies for oral delivery of biomacromolecules have been proposed, including lipid based formulations and polymer-based particulate drug delivery systems (DDS). The aim of this review is to summarize the existing knowledge about oral delivery of peptide/protein drugs and to provide an overview of formulationand characterization strategies. For a better understanding of the challenges in oral delivery of peptide/protein drugs, the composition of GI fluids and the digestion processes of different kinds of excipients in the GI tract are summarized. Additionally, the paper provides an overview of recent studies on characterization of solid drug carriers for peptide/protein drugs, drug distribution in particles, drug release and stability in simulated GI fluids, as well as the absorption of peptide/protein drugs in cell-based models. The use of biorelevant media when applicable can increase the knowledge about the quality of DDS for oral protein delivery. Hopefully, the knowledge provided in this review will aid the establishment of improved biorelevant models capable of forecasting the performance of particulate DDS for oral peptide/protein delivery.

Transdermal drug delivery

PubMed Central

Prausnitz, Mark R.; Langer, Robert

2009-01-01

Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, non-cavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin’s barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase impact on medicine. PMID:18997767

Compartmental transport model of microbicide delivery by an intravaginal ring

PubMed Central

Geonnotti, Anthony R.; Katz, David F.

2010-01-01

Topical antimicrobials, or microbicides, are being developed to prevent HIV transmission through local, mucosal delivery of antiviral compounds. While hydrogel vehicles deliver the majority of current microbicide products, intravaginal rings (IVRs) are an alternative microbicide modality in preclinical development. IVRs provide a long-term dosing alternative to hydrogel use, and might provide improved user adherence. IVR efficacy requires sustained delivery of antiviral compounds to the entire vaginal compartment. A two-dimensional, compartmental vaginal drug transport model was created to evaluate the delivery of drugs from an intravaginal ring. The model utilized MRI-derived ring geometry and location, experimentally defined ring fluxes and vaginal fluid velocities, and biophysically relevant transport theory. Model outputs indicated the presence of potentially inhibitory concentrations of antiviral compounds along the entire vaginal canal within 24 hours following IVR insertion. Distributions of inhibitory concentrations of antiviral compounds were substantially influenced by vaginal fluid flow and production, while showing little change due to changes in diffusion coefficients or ring fluxes. Additionally, model results were predictive of in vivo concentrations obtained in clinical trials. Overall, this analysis initiates a mechanistic computational framework, heretofore missing, to understand and evaluate the potential of IVRs for effective delivery of antiviral compounds. PMID:20222027

[Physicopharmaceutical characteristics of ulinastatin vaginal suppositories prepared in a hospital].

PubMed

Satake, Kiyoshi; Nakajima, Takanori; Iwata, Masanori; Fujikake, Yoshio; Kimura, Masayuki

2011-01-01

We studied a locally applied vaginal preparation (vaginal suppositories) of ulinastatin (urinary trypsin inhibitor, UTI), designed to threatened premature delivery and maintain pregnancy. Witepsol S55 was chosen as the basic component of the vaginal suppositories based on the physical pharmaceutical characteristics of three kinds of hard fats. The average particle size of the UTI aqueous injection was approximately 70% as compared with that of the UTI lyophilized product, used as the base material for the preparation of UTI vaginal suppositories. We compared the physical pharmaceutical properties of UTI vaginal suppositories with water contents of 2.5%, 5.0%, and 7.5%, respectively. Preparation strength negatively correlated with the water content. The coefficient of viscosity positively correlated with the water content of the preparation. UTI vaginal suppositories with a water content of 5.0% had the highest average drug release rate on moment analysis. A comprehensive evaluation of the properties of UTI vaginal suppositories, including high strength due to disintegration resistance, the coefficient of viscosity and its influence on local retention, and drug release and its influence on the duration of effect, indicated that a 5.0% UTI aqueous solution for injection combined with Witepsol S55 as the base was the optimal formulation for the hospital preparation of vaginal suppositories.

Aerobic vaginitis in pregnancy.

PubMed

Donders, Ggg; Bellen, G; Rezeberga, D

2011-09-01

Aerobic vaginitis (AV) is an alteration in vaginal bacterial flora that differs from bacterial vaginosis (BV). AV is characterised by an abnormal vaginal microflora accompanied by an increased localised inflammatory reaction and immune response, as opposed to the suppressed immune response that is characteristic of BV. Given the increased local production of interleukin (IL)-1, IL-6 and IL-8 associated with AV during pregnancy, not surprisingly AV is associated with an increased risk of preterm delivery, chorioamnionitis and funisitis of the fetus. There is no consensus on the optimal treatment for AV in pregnant or non-pregnant women, but a broader spectrum drug such as clindamycin is preferred above metronidazole to prevent infection-related preterm birth. The exact role of AV in pregnancy, the potential benefit of screening, and the use of newer local antibiotics, disinfectants, probiotics and immune modulators need further study. © 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.

Characteristics in the first vaginal birth and their association with mode of delivery in the subsequent birth.

PubMed

Chen, Jian Sheng; Ford, Jane B; Ampt, Amanda; Simpson, Judy M; Roberts, Christine L

2013-03-01

The extent to which complications or adverse outcomes in a first vaginal birth may contribute to mode of delivery in the next birth remains unclear. This study examines the impact of the first birth on subsequent mode of delivery. The study population included women with a first vaginal birth and a consecutive second birth. Data were obtained from linked birth and hospital records for the state of New South Wales, Australia 2000-09. The primary outcome was the mode of delivery for the second birth. Planned caesarean was modelled using logistic regression; intrapartum caesarean and instrumental delivery were modelled using multinomial logistic regression. Of the 114 287 second births, 4.2% were planned caesarean, 3.0% were intrapartum caesarean and 4.8% were instrumental deliveries. Adjusted risk factors from the first birth for a planned second birth caesarean were third to fourth degree tear [odds ratio (OR) = 5.0 [95% confidence interval (CI) 4.6, 5.4

Urinary incontinence after vaginal delivery or cesarean section.

PubMed

Borges, João Bosco Ramos; Guarisi, Telma; Camargo, Ana Carolina Marchesini de; Gollop, Thomaz Rafael; Machado, Rogério Bonassi; Borges, Pítia Cárita de Godoy

2010-06-01

To assess the prevalence of stress urinary incontinence, urge incontinence and mixed urinary incontinence among women residing in the city of Jundiaí (São Paulo, Brazil), and the relation between the type of incontinence and the obstetric history of these women. A cross-sectional community-based study was conducted. A total of 332 women were interviewed; they were seen for whatever reason at the public primary healthcare units of the city of Jundiaí, from March 2005 to April 2006. A pre-tested questionnaire was administered and consisted of questions used in the EPINCONT Study (Epidemiology of Incontinence in the County of Nord-Trondelag). Statistical analysis was carried out using the χ2 test and odds ratio (95%CI). Urinary incontinence was a complaint for 23.5% of the women interviewed. Stress urinary incontinence prevailed (50%), followed by mixed urinary incontinence (35%) and urge incontinence (15%). Being in the age group of 35-64 years, having a body mass index of 30 or greater and having had only vaginal delivery or cesarean section, with uterine contraction, regardless of the number of pregnancies, were factors associated with stress urinary incontinence. However, being in the age group of 55 or older, having a body mass index of 30 or greater and having had three or more pregnancies, only with vaginal deliveries, were factors associated with mixed urinary incontinence. One third of the interviewees complained of some type of urinary incontinence, and half of them presented stress urinary incontinence. Cesarean section, only when not preceded by contractions, was not associated with stress urinary incontinence. The body mass index is only relevant when the stress factor is present.

Polymers for Drug Delivery Systems

PubMed Central

Liechty, William B.; Kryscio, David R.; Slaughter, Brandon V.; Peppas, Nicholas A.

2012-01-01

Polymers have played an integral role in the advancement of drug delivery technology by providing controlled release of therapeutic agents in constant doses over long periods, cyclic dosage, and tunable release of both hydrophilic and hydrophobic drugs. From early beginnings using off-the-shelf materials, the field has grown tremendously, driven in part by the innovations of chemical engineers. Modern advances in drug delivery are now predicated upon the rational design of polymers tailored for specific cargo and engineered to exert distinct biological functions. In this review, we highlight the fundamental drug delivery systems and their mathematical foundations and discuss the physiological barriers to drug delivery. We review the origins and applications of stimuli-responsive polymer systems and polymer therapeutics such as polymer-protein and polymer-drug conjugates. The latest developments in polymers capable of molecular recognition or directing intracellular delivery are surveyed to illustrate areas of research advancing the frontiers of drug delivery. PMID:22432577

Childbirth Education Class and Birth Plans Are Associated with a Vaginal Delivery.

PubMed

Afshar, Yalda; Wang, Erica T; Mei, Jenny; Esakoff, Tania F; Pisarska, Margareta D; Gregory, Kimberly D

2017-03-01

To determine whether the mode of delivery was different between women who attended childbirth education (CBE) class, had a birth plan, or both compared with those who did not attend CBE class or have a birth plan. This is a retrospective cross-sectional study of women who delivered singleton gestations > 24 weeks at our institution between August 2011 and June 2014. Based on a self-report at the time of admission for labor, women were stratified into four categories: those who attended a CBE class, those with a birth plan, both, and those with neither CBE or birth plan. The primary outcome was the mode of delivery. Multivariate logistic regression analyses adjusting for clinical covariates were performed. In this study, 14,630 deliveries met the inclusion criteria: 31.9 percent of the women attended CBE class, 12.0 percent had a birth plan, and 8.8 percent had both. Women who attended CBE or had a birth plan were older (p < 0.001), more likely to be nulliparous (p < 0.001), had a lower body mass index (p < 0.001), and were less likely to be African-American (p < 0.001). After adjusting for significant covariates, women who participated in either option or both had higher odds of a vaginal delivery (CBE: OR 1.26 [95% CI 1.15-1.39]; birth plan: OR 1.98 [95% CI 1.56-2.51]; and both: OR 1.69 [95% CI 1.46-1.95]) compared with controls. Attending CBE class and/or having a birth plan were associated with a vaginal delivery. These findings suggest that patient education and birth preparation may influence the mode of delivery. CBE and birth plans could be used as quality improvement tools to potentially decrease cesarean rates. © 2016 Wiley Periodicals, Inc.

Ocular drug delivery systems: An overview

PubMed Central

Patel, Ashaben; Cholkar, Kishore; Agrahari, Vibhuti; Mitra, Ashim K

2014-01-01

The major challenge faced by today’s pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration, especially for the treatment of anterior segment diseases. Delivery of drugs to the targeted ocular tissues is restricted by various precorneal, dynamic and static ocular barriers. Also, therapeutic drug levels are not maintained for longer duration in target tissues. In the past two decades, ocular drug delivery research acceleratedly advanced towards developing a novel, safe and patient compliant formulation and drug delivery devices/techniques, which may surpass these barriers and maintain drug levels in tissues. Anterior segment drug delivery advances are witnessed by modulation of conventional topical solutions with permeation and viscosity enhancers. Also, it includes development of conventional topical formulations such as suspensions, emulsions and ointments. Various nanoformulations have also been introduced for anterior segment ocular drug delivery. On the other hand, for posterior ocular delivery, research has been immensely focused towards development of drug releasing devices and nanoformulations for treating chronic vitreoretinal diseases. These novel devices and/or formulations may help to surpass ocular barriers and associated side effects with conventional topical drops. Also, these novel devices and/or formulations are easy to formulate, no/negligibly irritating, possess high precorneal residence time, sustain the drug release, and enhance ocular bioavailability of therapeutics. An update of current research advancement in ocular drug delivery necessitates and helps drug delivery scientists to modulate their think process and develop novel and safe drug delivery strategies. Current review intends to summarize the existing conventional formulations for ocular delivery and their advancements followed by current nanotechnology based formulation developments

Ocular drug delivery systems: An overview.

PubMed

Patel, Ashaben; Cholkar, Kishore; Agrahari, Vibhuti; Mitra, Ashim K

The major challenge faced by today's pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration, especially for the treatment of anterior segment diseases. Delivery of drugs to the targeted ocular tissues is restricted by various precorneal, dynamic and static ocular barriers. Also, therapeutic drug levels are not maintained for longer duration in target tissues. In the past two decades, ocular drug delivery research acceleratedly advanced towards developing a novel, safe and patient compliant formulation and drug delivery devices/techniques, which may surpass these barriers and maintain drug levels in tissues. Anterior segment drug delivery advances are witnessed by modulation of conventional topical solutions with permeation and viscosity enhancers. Also, it includes development of conventional topical formulations such as suspensions, emulsions and ointments. Various nanoformulations have also been introduced for anterior segment ocular drug delivery. On the other hand, for posterior ocular delivery, research has been immensely focused towards development of drug releasing devices and nanoformulations for treating chronic vitreoretinal diseases. These novel devices and/or formulations may help to surpass ocular barriers and associated side effects with conventional topical drops. Also, these novel devices and/or formulations are easy to formulate, no/negligibly irritating, possess high precorneal residence time, sustain the drug release, and enhance ocular bioavailability of therapeutics. An update of current research advancement in ocular drug delivery necessitates and helps drug delivery scientists to modulate their think process and develop novel and safe drug delivery strategies. Current review intends to summarize the existing conventional formulations for ocular delivery and their advancements followed by current nanotechnology based formulation developments

Twin Birth Study: 2-year neurodevelopmental follow-up of the randomized trial of planned cesarean or planned vaginal delivery for twin pregnancy.

PubMed

Asztalos, Elizabeth V; Hannah, Mary E; Hutton, Eileen K; Willan, Andrew R; Allen, Alexander C; Armson, B Anthony; Gafni, Amiram; Joseph, K S; Ohlsson, Arne; Ross, Susan; Sanchez, J Johanna; Mangoff, Kathryn; Barrett, Jon F R

2016-03-01

The Twin Birth Study randomized women with uncomplicated pregnancies, between 32(0/7)-38(6/7) weeks' gestation where the first twin was in cephalic presentation, to a policy of either a planned cesarean or planned vaginal delivery. The primary analysis showed that planned cesarean delivery did not increase or decrease the risk of fetal/neonatal death or serious neonatal morbidity as compared with planned vaginal delivery. This study presents the secondary outcome of death or neurodevelopmental delay at 2 years of age. A total of 4603 children from the initial cohort of 5565 fetuses/infants (83%) contributed to the outcome of death or neurodevelopmental delay. Surviving children were screened using the Ages and Stages Questionnaire with abnormal scores validated by a clinical neurodevelopmental assessment. The effect of planned cesarean vs planned vaginal delivery on death or neurodevelopmental delay was quantified using a logistic model to control for stratification variables and using generalized estimating equations to account for the nonindependence of twin births. Baseline maternal, pregnancy, and infant characteristics were similar. Mean age at assessment was 26 months. There was no significant difference in the outcome of death or neurodevelopmental delay: 5.99% in the planned cesarean vs 5.83% in the planned vaginal delivery group (odds ratio, 1.04; 95% confidence interval, 0.77-1.41; P = .79). A policy of planned cesarean delivery provides no benefit to children at 2 years of age compared with a policy of planned vaginal delivery in uncomplicated twin pregnancies between 32(0/7)-38(6/7)weeks' gestation where the first twin is in cephalic presentation. Copyright © 2016 Elsevier Inc. All rights reserved.

Physically facilitating drug-delivery systems

PubMed Central

Rodriguez-Devora, Jorge I; Ambure, Sunny; Shi, Zhi-Dong; Yuan, Yuyu; Sun, Wei; Xu, Tao

2012-01-01

Facilitated/modulated drug-delivery systems have emerged as a possible solution for delivery of drugs of interest to pre-allocated sites at predetermined doses for predefined periods of time. Over the past decade, the use of different physical methods and mechanisms to mediate drug release and delivery has grown significantly. This emerging area of research has important implications for development of new therapeutic drugs for efficient treatments. This review aims to introduce and describe different modalities of physically facilitating drug-delivery systems that are currently in use for cancer and other diseases therapy. In particular, delivery methods based on ultrasound, electrical, magnetic and photo modulations are highlighted. Current uses and areas of improvement for these different physically facilitating drug-delivery systems are discussed. Furthermore, the main advantages and drawbacks of these technologies reviewed are compared. The review ends with a speculative viewpoint of how research is expected to evolve in the upcoming years. PMID:22485192

Meta-analysis of randomized controlled trials comparing 17α-hydroxyprogesterone caproate and vaginal progesterone for the prevention of recurrent spontaneous preterm delivery.

PubMed

Oler, Elizabeth; Eke, Ahizechukwu C; Hesson, Ashley

2017-07-01

Vaginal progesterone and 17α-hydroxyprogesterone (17α-OHP) are both used to prevent preterm delivery in women who have experienced spontaneous preterm delivery (SPTD) previously. Randomized trial data of the comparative effectiveness of these interventions have been mixed. To compare the efficacy of intramuscular 17α-OHP and vaginal progesterone in the prevention of recurrent SPTD. Cochrane Central Register of Controlled Trials, African Journals Online, Embase, Google Scholar, ISI Web of Science, LILACS, CINAHL, PubMed, and registers of ongoing trials were searched using keywords related to 17α-OHP, vaginal progesterone, and preterm delivery. Randomized controlled trials published between January 1, 1966, and November 30, 2016, comparing 17α-OHP and vaginal progesterone for the prevention of recurrent SPTD during singleton pregnancies were included. Study data were extracted and meta-analyses were performed when outcomes were comparable. The meta-analyses included data from three randomized trials. Lower rates of SPTD before 34 weeks (relative risk 0.71, 95% confidence interval 0.53-0.95) and before 32 weeks (relative risk 0.62, 95% confidence interval 0.40-0.94) of pregnancy were observed among patients treated with vaginal progesterone. Vaginal progesterone and 17α-OHP were comparable for the prevention of recurrent SPTD in singleton pregnancies; vaginal progesterone could be superior. © 2017 International Federation of Gynecology and Obstetrics.

Decreased rates of nosocomial endometritis and urinary tract infection after vaginal delivery in a French surveillance network, 1997-2003.

PubMed

Ayzac, Louis; Caillat-Vallet, Emmanuelle; Girard, Raphaële; Chapuis, Catherine; Depaix, Florence; Dumas, Anne-Marie; Gignoux, Chantal; Haond, Catherine; Lafarge-Leboucher, Joëlle; Launay, Carine; Tissot-Guerraz, Françoise; Vincent, Agnès; Fabry, Jacques

2008-06-01

To identify independent risk factors for endometritis and urinary tract infection (UTI) after vaginal delivery, and to monitor changes in nosocomial infection rates and derive benchmarks for prevention. Prospective study. We analyzed routine surveillance data for all vaginal deliveries between January 1997 and December 2003 at 66 maternity units participating in the Mater Sud-Est surveillance network. Adjusted odds ratios for risk of endometritis or UTI were obtained using a logistic regression model. The overall incidence rates were 0.5% for endometritis and 0.3% for UTI. There was a significant decrease in the incidence and risk of endometritis but not of UTI during the 7-year period. Significant risk factors for endometritis were fever during labor, parity of 1, and instrumental delivery and/or manual removal of the placenta. Significant risk factors for UTI were urinary infection on admission, premature rupture of membranes (more than 12 hours before admission), blood loss of more than 800 mL, parity of 1, instrumental delivery, and receipt of more than 5 vaginal digital examinations. Each maternity unit received a poster showing graphs of the number of expected and observed cases of UTI and endometritis associated with vaginal deliveries, which enabled each maternity unit to determine their rank within the network and to initiate prevention programs. Although routine surveillance means additional work for maternity units, our results demonstrate the usefulness of regular targeted monitoring of risk factors and of the most common nosocomial infections in obstetrics. Most of the information needed for monitoring is already present in the patients' records.

Reversibly pH-responsive polyurethane membranes for on-demand intravaginal drug delivery.

PubMed

Kim, Seungil; Chen, Yufei; Ho, Emmanuel A; Liu, Song

2017-01-01

To provide better protection for women against sexually transmitted infections, on-demand intravaginal drug delivery was attempted by synthesizing reversibly pH-sensitive polyether-polyurethane copolymers using poly(ethylene glycol) (PEG) and 1,4-bis(2-hydroxyethyl)piperazine (HEP). Chemical structure and thermo-characteristics of the synthesized polyurethanes were confirmed by attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), 1 H-nuclear magnetic resonance ( 1 H-NMR), and melting point testing. Membranes were cast by solvent evaporation method using the prepared pH-sensitive polyurethanes. The impact of varying pH on membrane swelling and surface morphology was evaluated via swelling ratio change and scanning electron microscopy (SEM). The prepared pH-responsive membranes showed two times higher swelling ratio at pH 4 than pH 7 and pH-triggered switchable surface morphology change. The anionic anti-inflammatory drug diclofenac sodium (NaDF) was used as a model compound for release studies. The prepared pH-responsive polyurethane membranes allowed continuous NaDF release for 24h and around 20% release of total NaDF within 3h at pH 7 but little-to-no drug release at pH 4.5. NaDF permeation across the prepared membranes demonstrated a reversible pH-responsiveness. The pH-responsive polyurethane membranes did not show any noticeable negative impact on vaginal epithelial cell viability or induction of pro-inflammatory cytokine production compared to controls. Overall, the non-cytotoxic HEP-based pH-responsive polyurethane demonstrated its potential to be used in membrane-based implants such as intravaginal rings to achieve on-demand "on-and-off" intravaginal drug delivery. A reversible and sharp switch between "off" and "on" drug release is achieved for the first time through new pH-sensitive polyurethane membranes, which can serve as window membranes in reservoir-type intravaginal rings for on-demand drug delivery to prevent sexually

Biomaterials for drug delivery systems.

PubMed

Buckles, R G

1983-01-01

Drug delivery systems have unusual materials requirements which derive mainly from their therapeutic role: to administer drugs over prolonged periods of time at rates that are independent of patient-to-patient variables. The chemical nature of the surfaces of such devices may stimulate biorejection processes which can be enhanced or suppressed by the simultaneous presence of the drug that is being administered. Selection of materials for such systems is further complicated by the need for compatibility with the drug contained within the system. A review of selected drug delivery systems is presented. This leads to a definition of the technologies required to develop successfully such systems as well as to categorize the classes of drug delivery systems available to the therapist. A summary of the applications of drug delivery systems will also be presented. There are five major challenges to the biomaterials scientist: (1) how to minimize the influence on delivery rate of the transient biological response that accompanies implantation of any object; (2) how to select a composition, size, shape, and flexibility that optimizes biocompatibility; (3) how to make an intravascular delivery system that will retain long-term functionality; (4) how to make a percutaneous lead for those delivery systems that cannot be implanted but which must retain functionality for extended periods; and (5) how to make biosensors of adequate compatibility and stability to use with the ultimate drug delivery system-a system that operates with feedback control.

Novel Spray Dried Glycerol 2-Phosphate Cross-Linked Chitosan Microparticulate Vaginal Delivery System—Development, Characterization and Cytotoxicity Studies

PubMed Central

Szymańska, Emilia; Szekalska, Marta; Czarnomysy, Robert; Lavrič, Zoran; Srčič, Stane; Miltyk, Wojciech; Winnicka, Katarzyna

2016-01-01

Chitosan microparticulate delivery systems containing clotrimazole were prepared by a spray drying technique using glycerol 2-phosphate as an ion cross-linker. The impact of a cross-linking ratio on microparticle characteristics was evaluated. Drug-free and drug-loaded unmodified or ion cross-linked chitosan microparticles were examined for the in vitro cytotoxicity in VK2/E6E7 human vaginal epithelial cells. The presence of glycerol 2-phosphate influenced drug loading and encapsulation efficacy in chitosan microparticles. By increasing the cross-linking ratio, the microparticles with lower diameter, moisture content and smoother surface were observed. Mucoadhesive studies displayed that all formulations possessed mucoadhesive properties. The in vitro release profile of clotrimazole was found to alter considerably by changing the glycerol 2-phosphate/chitosan ratio. Results from cytotoxicity studies showed occurrence of apoptotic cells in the presence of chitosan and ion cross-linked chitosan microparticles, followed by a loss of membrane potential suggesting that cell death might go through the mitochondrial apoptotic pathway. PMID:27690062

Development of starch based mucoadhesive vaginal drug delivery systems for application in veterinary medicine.

PubMed

Gök, Mehmet Koray; Özgümüş, Saadet; Demir, Kamber; Cirit, Ümüt; Pabuccuoğlu, Serhat; Cevher, Erdal; Özsoy, Yıldız; Bacınoğlu, Süleyman

2016-01-20

The aim of this study was to prepare and evaluate the mucoadhesive, biocompatible and biodegradable progesterone containing vaginal tablets based on modified starch copolymers for the estrus synchronization of ewes. Starch-graft-poly(acrylic acid) copolymers (S-g-PAA) were synthesized and characterized. The vaginal tablets were fabricated with S-g-PAA and their equilibrium swelling degree (Qe) and matrix erosion (ME%) were determined in lactate buffer solution. In vitro, mucoadhesive properties of the tablets were investigated by using ewe vaginal mucosa and in vivo residence time were also investigated. In vitro and in vivo progesterone release profiles from the tablets were compared with two commercial products. Tablet formulation containing wheat starch based grafted copolymer (WS-g-PAA)gc indicated promising results and might be convenient as an alternative product to the commercial products in veterinary medicine. Copyright © 2015 Elsevier Ltd. All rights reserved.

Calcium silicate-based drug delivery systems.

PubMed

Zhu, Ying-Jie; Guo, Xiao-Xuan; Sham, Tsun-Kong

2017-02-01

Compared with other inorganic materials such as silica, metal oxides, noble metals and carbon, calcium silicate-based materials, especially nanostructured calcium silicate materials, have high biocompatibility, bioactivity and biodegradability, high specific surface area, nanoporous/hollow structure, high drug-loading capacity, pH-responsive drug release behavior and desirable drug release properties, and thus they are promising for the application in drug delivery. Calcium silicate-based drug delivery systems have a long drug-release time, which can significantly prolong the therapeutic effect of drugs. Another advantage of calcium silicate-based drug delivery systems is their pH-responsive drug release property, which can act as an ideal platform for targeted drug delivery. Areas covered: In recent years, studies have been carried out on calcium silicate-based drug delivery systems, and important results and insights have been documented. This article is not intended to offer a comprehensive review on the research on calcium silicate-based drug delivery systems, but presents some examples reported in the literature, and includes new insights obtained by tracking the interactions between drug molecules and calcium silicate carriers on the molecular level using the synchrotron-based X-ray spectroscopy. Expert opinion: Finally, our opinions on calcium silicate-based drug delivery systems are provided, and several research directions for the future studies are proposed.

Spontaneous vaginal delivery in the birth-chair versus in the conventional dorsal position: a matched controlled comparison.

PubMed

Scholz, H S; Benedicic, C; Arikan, M G; Haas, J; Petru, E

2001-09-17

The aim of the study was to assess the effect of a birth-chair on obstetric outcome. We reviewed the hospital records of 220 consecutive pregnant women who gave birth on a birth-chair at our institution. The control group consisted of 440 pregnant women who preceded and followed the index cases and who had spontaneous vaginal deliveries in the conventional dorsal supine position. The controls were matched for parity and for the attending mid-wife. Patients who delivered in the birth-chair had significantly lower rates of episiotomy and manual separation of the placenta. The umbilical blood cord pH was significantly higher in neonates of the birth-chair group. The duration of labour, rate of perineal and vaginal injury, Apgar scores and rate of admission to a neonatal intermediate care unit were not influenced by the mode of delivery. Our data support previous studies that a birth-chair delivery may be a safe alternative to conventional delivery in the supine position.

Microfabrication for Drug Delivery

PubMed Central

Koch, Brendan; Rubino, Ilaria; Quan, Fu-Shi; Yoo, Bongyoung; Choi, Hyo-Jick

2016-01-01

This review is devoted to discussing the application of microfabrication technologies to target challenges encountered in life processes by the development of drug delivery systems. Recently, microfabrication has been largely applied to solve health and pharmaceutical science issues. In particular, fabrication methods along with compatible materials have been successfully designed to produce multifunctional, highly effective drug delivery systems. Microfabrication offers unique tools that can tackle problems in this field, such as ease of mass production with high quality control and low cost, complexity of architecture design and a broad range of materials. Presented is an overview of silicon- and polymer-based fabrication methods that are key in the production of microfabricated drug delivery systems. Moreover, the efforts focused on studying the biocompatibility of materials used in microfabrication are analyzed. Finally, this review discusses representative ways microfabrication has been employed to develop systems delivering drugs through the transdermal and oral route, and to improve drug eluting implants. Additionally, microfabricated vaccine delivery systems are presented due to the great impact they can have in obtaining a cold chain-free vaccine, with long-term stability. Microfabrication will continue to offer new, alternative solutions for the development of smart, advanced drug delivery systems. PMID:28773770

Third and Fourth Degree Perineal Injury After Vaginal Delivery: Does Race Make a Difference?

PubMed Central

de Silva, Kanoe-Lehua; Tsai, Pai-Jong Stacy; Kon, Leanne M; Kessel, Bruce; Seto, Todd; Kaneshiro, Bliss

2014-01-01

Severe perineal injury (third and fourth degree laceration) at the time of vaginal delivery increases the risk of fecal incontinence, chronic perineal pain, and dyspareunia.1–5 Studies suggest the prevalence of severe perineal injury may vary by racial group.6 The purpose of the current study was to examine rates of severe perineal injury in different Asian and Pacific Islander subgroups. A retrospective cohort study was performed among all patients who had a vaginal delivery at Queens Medical Center in Honolulu, Hawai‘i between January 1, 2002 and December 31, 2003. Demographic and health related variables were obtained for each participant. Maternal race/ethnicity (Japanese, Filipino, Chinese, other Asian, Part-Hawaiian/Hawaiian, Micronesian, other Pacific Islander, Caucasian, multiracial [non-Hawaiian], and other) was self-reported by the patient at the time admission. The significance of associations between racial/ethnic groups and demographic and health related variables was determined using chi-square tests for categorical variables and analysis of variance for continuous factors. Multiple logistic regression was performed to adjust for potential confounders when examining severe laceration rates. A total of 1842 subjects met inclusion criteria. The proportion of severe perineal lacerations did not differ significantly between racial groups. In the multiple logistic regression analysis, operative vaginal delivery was related to both race and severe perineal laceration. However, despite adjusting for this variable, race was not associated with an increased risk of having a severe laceration (P = .70). The results of this study indicate the risk of severe perineal laceration does not differ based on maternal race/ethnicity. PMID:24660124

Improvement of Tenofovir vaginal release from hydrophilic matrices through drug granulation with hydrophobic polymers.

PubMed

Notario-Pérez, Fernando; Martín-Illana, Araceli; Cazorla-Luna, Raúl; Ruiz-Caro, Roberto; Peña, Juan; Veiga, María-Dolores

2018-05-30

Sustained-release vaginal microbicides hold out great hope for the prevention of sexual transmission of HIV from men to women. Tenofovir (TFV) -an antiretroviral drug- sustained-release vaginal compacts combining two release control systems (by drug-loading granules with hydrophobic polymers and incorporating them in a hydrophilic matrix) are proposed in this work as a possible microbicide. The polymers used for the drug granules are Eudragit® RS (ERS), an acrylic derivative, and Zein, a maize protein. The hydrophilic matrix is composed of a mixture of hydroxypropylmethyl cellulose (HPMC) and chitosan (CH). The thermal, microscopic, spectrophotometric and X-ray diffraction analysis showed that the drug was not altered during the granulation process. Studies of TFV release, swelling and ex vivo mucoadhesion were subsequently performed on simulated vaginal fluid. The formulation whereby TFV is granulated using twice its weight in ERS, and then including these granules in a matrix in which the CH predominates over HPMC, allows the sustained release of TFV for 144 h, mucoadhesion to the vaginal mucosa for 150 h and a moderate swelling, making it the most suitable formulation of all those studied. These compacts would therefore offer women protection against the sexual acquisition of HIV. Copyright © 2018 Elsevier B.V. All rights reserved.

Intracochlear Drug Delivery Systems

PubMed Central

Borenstein, Jeffrey T.

2011-01-01

Introduction Advances in molecular biology and in the basic understanding of the mechanisms associated with sensorineural hearing loss and other diseases of the inner ear, are paving the way towards new approaches for treatments for millions of patients. However, the cochlea is a particularly challenging target for drug therapy, and new technologies will be required to provide safe and efficacious delivery of these compounds. Emerging delivery systems based on microfluidic technologies are showing promise as a means for direct intracochlear delivery. Ultimately, these systems may serve as a means for extended delivery of regenerative compounds to restore hearing in patients suffering from a host of auditory diseases. Areas covered in this review Recent progress in the development of drug delivery systems capable of direct intracochlear delivery is reviewed, including passive systems such as osmotic pumps, active microfluidic devices, and systems combined with currently available devices such as cochlear implants. The aim of this article is to provide a concise review of intracochlear drug delivery systems currently under development, and ultimately capable of being combined with emerging therapeutic compounds for the treatment of inner ear diseases. Expert Opinion Safe and efficacious treatment of auditory diseases will require the development of microscale delivery devices, capable of extended operation and direct application to the inner ear. These advances will require miniaturization and integration of multiple functions, including drug storage, delivery, power management and sensing, ultimately enabling closed-loop control and timed-sequence delivery devices for treatment of these diseases. PMID:21615213

Obstetric outcome associated with trial of labor in women with three prior cesarean delivery and at least one prior vaginal birth in an area with a particularly high rate of cesarean delivery.

PubMed

Vigorito, Roberto; Montemagno, Rodolfo; Saccone, Gabriele; De Stefano, Renato

2016-11-01

The objective of this study is to evaluate maternal and neonatal outcomes associated with trial of labor after cesarean (TOLAC) in women with three prior cesarean delivery (CD) and at least one prior vaginal delivery. This is a retrospective study using data collected from clinical records of women three prior CD and at least one prior vaginal delivery who were referred to our unit. Maternal and perinatal outcomes were compared between women with three prior CD who underwent TOLAC and those who underwent planned repeated CD (i.e. control group). The primary outcome was a composite of maternal complications including at least one of the followings: need for blood transfusion, uterine rupture, hysterectomy, and admission to intensive care unit. Fifty singleton gestations with three prior CD at with at least one prior vaginal birth were analyzed. Of them, 10 accepted to undergo TOLAC. Of the 10 women who underwent TOLAC, nine had vaginal birth and one had CD for non-reassuring pattern. We found no significant differences in the primary outcome, in need for blood transfusion, in the incidence of uterine rupture, hysterectomy, and admission to intensive care unit comparing TOLAC group with controls. TOLAC in women with three prior CD and at least one prior vaginal delivery is a viable option and is not associated with higher risk of adverse maternal or fetal outcomes.

Oral Drug Delivery Systems Comprising Altered Geometric Configurations for Controlled Drug Delivery

PubMed Central

Moodley, Kovanya; Pillay, Viness; Choonara, Yahya E.; du Toit, Lisa C.; Ndesendo, Valence M. K.; Kumar, Pradeep; Cooppan, Shivaan; Bawa, Priya

2012-01-01

Recent pharmaceutical research has focused on controlled drug delivery having an advantage over conventional methods. Adequate controlled plasma drug levels, reduced side effects as well as improved patient compliance are some of the benefits that these systems may offer. Controlled delivery systems that can provide zero-order drug delivery have the potential for maximizing efficacy while minimizing dose frequency and toxicity. Thus, zero-order drug release is ideal in a large area of drug delivery which has therefore led to the development of various technologies with such drug release patterns. Systems such as multilayered tablets and other geometrically altered devices have been created to perform this function. One of the principles of multilayered tablets involves creating a constant surface area for release. Polymeric materials play an important role in the functioning of these systems. Technologies developed to date include among others: Geomatrix® multilayered tablets, which utilizes specific polymers that may act as barriers to control drug release; Procise®, which has a core with an aperture that can be modified to achieve various types of drug release; core-in-cup tablets, where the core matrix is coated on one surface while the circumference forms a cup around it; donut-shaped devices, which possess a centrally-placed aperture hole and Dome Matrix® as well as “release modules assemblage”, which can offer alternating drug release patterns. This review discusses the novel altered geometric system technologies that have been developed to provide controlled drug release, also focusing on polymers that have been employed in such developments. PMID:22312236

Odon device for instrumental vaginal deliveries: results of a medical device pilot clinical study.

PubMed

Schvartzman, Javier A; Krupitzki, Hugo; Merialdi, Mario; Betrán, Ana Pilar; Requejo, Jennifer; Nguyen, My Huong; Vayena, Effy; Fiorillo, Angel E; Gadow, Enrique C; Vizcaino, Francisco M; von Petery, Felicitas; Marroquin, Victoria; Cafferata, María Luisa; Mazzoni, Agustina; Vannevel, Valerie; Pattinson, Robert C; Gülmezoglu, A Metin; Althabe, Fernando; Bonet, Mercedes

2018-03-12

A prolonged and complicated second stage of labour is associated with serious perinatal complications. The Odon device is an innovation intended to perform instrumental vaginal delivery presently under development. We present an evaluation of the feasibility and safety of delivery with early prototypes of this device from an early terminated clinical study. Hospital-based, multi-phased, open-label, pilot clinical study with no control group in tertiary hospitals in Argentina and South Africa. Multiparous and nulliparous women, with uncomplicated singleton pregnancies, were enrolled during the third trimester of pregnancy. Delivery with Odon device was attempted under non-emergency conditions during the second stage of labour. The feasibility outcome was delivery with the Odon device defined as successful expulsion of the fetal head after one-time application of the device. Of the 49 women enrolled, the Odon device was inserted successfully in 46 (93%), and successful Odon device delivery as defined above was achieved in 35 (71%) women. Vaginal, first and second degree perineal tears occurred in 29 (59%) women. Four women had cervical tears. No third or fourth degree perineal tears were observed. All neonates were born alive and vigorous. No adverse maternal or infant outcomes were observed at 6-weeks follow-up for all dyads, and at 1 year for the first 30 dyads. Delivery using the Odon device is feasible. Observed genital tears could be due to the device or the process of delivery and assessment bias. Evaluating the effectiveness and safety of the further developed prototype of the BD Odon Device™ will require a randomized-controlled trial. ANZCTR ACTRN12613000141741 Registered 06 February 2013. Retrospectively registered.

Over-the-counter vaginal contraceptive and spermicide drug products containing nonoxynol 9; required labeling. Final rule.

PubMed

2007-12-19

The Food and Drug Administration (FDA) is issuing a final rule establishing new warning statements and other labeling information for all over-the-counter (OTC) vaginal contraceptive drug products (also known as spermicides, hereinafter referred to as vaginal contraceptives or vaginal contraceptives/spermicides) containing nonoxynol 9 (N9). These warning statements will advise consumers that vaginal contraceptives/spermicides containing N9 do not protect against infection from the human immunodeficiency virus (HIV), the virus that causes acquired immunodeficiency syndrome (AIDS), or against getting other sexually transmitted diseases (STDs). The warnings and labeling information will also advise consumers that use of vaginal contraceptives and spermicides containing N9 can irritate the vagina and rectum and may increase the risk of getting the AIDS virus (HIV) from an infected partner. This final rule is part of FDA's ongoing review of OTC drug products. FDA is issuing this final rule after considering public comments on its proposed regulation, and all relevant data and information on N9 that have come to our attention.

Pattern of episiotomy use & its immediate complications among vaginal deliveries in 18 tertiary care hospitals in India

PubMed Central

Singh, Shalini; Thakur, Tushita; Chandhiok, Nomita; Dhillon, Balwan Singh

2016-01-01

Background & objectives: In developed countries, efforts have been made to restrict episiotomy practice. However, in developing countries the episiotomy rates continue to be high. This study was conducted to evaluate the pattern of episiotomy use and its immediate complications among women delivering at tertiary level public hospitals in India. Methods: Prospective data of all women undergoing vaginal delivery including instrumental delivery were collected daily from the labour room registers of the 18 tertiary care hospitals on a structured proforma. Weekly data from all sites were sent to a central unit for compilation and analysis. Odds ratio was used to compare the proportion of genital trauma among women with and without episiotomy both in nulliparous and multiparous women. Results: Among 1,20,243 vaginal deliveries, episiotomy was performed in 63.4 per cent (n=76,305) cases. Nulliparaous women were 8.8 times more likely to undergo episiotomy than multiparous women. The various genital tract injuries reported were first degree perineal tear (n=4805, 3.9%), second degree perineal tear (n=1082, 0.9%), third and fourth degree perineal tear (n=186, 0.2%), anterior vaginal trauma requiring suturing (n=490, 0.4%), extension of episiotomy/vaginal laceration/excessive bleeding from episiotomy or tear (n=177, 0.15%), vulval/vaginal haematoma (n=70, 0.06%) and cervical tear (n=108, 0.08%). The combined rate of third and fourth degree perineal tears was observed to be significantly lower (P<0.001) among nullipara who received episiotomy (0.13%) compared to those who delivered without episiotomy (0.62%). Interpretations & conclusions: Significantly lower rates of third or fourth degree perineal tear were seen among nulliparous women undergoing episiotomy. The risk and benefit of episiotomy and its complications need to be evaluated through randomized clinical trials in the Indian context. PMID:27377504

Safety of a silicone elastomer vaginal ring as potential microbicide delivery method in African women: A Phase 1 randomized trial.

PubMed

Nel, Annaléne; Martins, Janine; Bekker, Linda-Gail; Ramjee, Gita; Masenga, Gileard; Rees, Helen; van Niekerk, Neliëtte

2018-01-01

Women in sub-Saharan Africa are in urgent need of female-initiated human immunodeficiency virus (HIV) preventative methods. Vaginal rings are one dosage form in development for delivery of HIV microbicides. However, African women have limited experience with vaginal rings. This Phase I, randomized, crossover trial assessed and compared the safety, acceptability and adherence of a silicone elastomer placebo vaginal ring, intended as a microbicide delivery method, inserted for a 12-week period in healthy, HIV-negative, sexually active women in South Africa and Tanzania. 170 women, aged 18 to 35 years were enrolled with 88 women randomized to Group A, using a placebo vaginal ring for 12 weeks followed by a 12-week safety observation period. 82 women were randomized to Group B and observed for safety first, followed by a placebo vaginal ring for 12 weeks. Safety was assessed by clinical laboratory assessments, pelvic/colposcopy examinations and adverse events. Possible carry-over effect was addressed by ensuring no signs or symptoms of genital irritation at crossover. No safety concerns were identified for any safety variables assessed during the trial. No serious adverse events were reported considered related to the placebo vaginal ring. Vaginal candidiasis was the most common adverse event occurring in 11% of participants during each trial period. Vaginal discharge (2%), vaginal odour (2%), and bacterial vaginitis (2%) were assessed as possibly or probably related to the vaginal ring. Thirty-four percent of participants had sexually transmitted infections (STIs) at screening, compared to 12% of participants who tested positive for STIs at crossover and the final trial visit. Three participants (2%) tested HIV positive during the trial. The silicone elastomer vaginal ring had no safety concerns, demonstrating a profile favorable for further development for topical release of antiretroviral-based microbicides.

Safety of a silicone elastomer vaginal ring as potential microbicide delivery method in African women: A Phase 1 randomized trial

PubMed Central

Nel, Annaléne; Bekker, Linda-Gail; Ramjee, Gita; Masenga, Gileard; Rees, Helen; van Niekerk, Neliëtte

2018-01-01

Background Women in sub-Saharan Africa are in urgent need of female-initiated human immunodeficiency virus (HIV) preventative methods. Vaginal rings are one dosage form in development for delivery of HIV microbicides. However, African women have limited experience with vaginal rings. Objectives This Phase I, randomized, crossover trial assessed and compared the safety, acceptability and adherence of a silicone elastomer placebo vaginal ring, intended as a microbicide delivery method, inserted for a 12-week period in healthy, HIV-negative, sexually active women in South Africa and Tanzania. Methods 170 women, aged 18 to 35 years were enrolled with 88 women randomized to Group A, using a placebo vaginal ring for 12 weeks followed by a 12-week safety observation period. 82 women were randomized to Group B and observed for safety first, followed by a placebo vaginal ring for 12 weeks. Safety was assessed by clinical laboratory assessments, pelvic/colposcopy examinations and adverse events. Possible carry-over effect was addressed by ensuring no signs or symptoms of genital irritation at crossover. Results No safety concerns were identified for any safety variables assessed during the trial. No serious adverse events were reported considered related to the placebo vaginal ring. Vaginal candidiasis was the most common adverse event occurring in 11% of participants during each trial period. Vaginal discharge (2%), vaginal odour (2%), and bacterial vaginitis (2%) were assessed as possibly or probably related to the vaginal ring. Thirty-four percent of participants had sexually transmitted infections (STIs) at screening, compared to 12% of participants who tested positive for STIs at crossover and the final trial visit. Three participants (2%) tested HIV positive during the trial. Conclusions The silicone elastomer vaginal ring had no safety concerns, demonstrating a profile favorable for further development for topical release of antiretroviral-based microbicides. PMID

Protein-Based Nanomedicine Platforms for Drug Delivery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma Ham, Aihui; Tang, Zhiwen; Wu, Hong

2009-08-03

Drug delivery systems have been developed for many years, however some limitations still hurdle the pace of going to clinical phase, for example, poor biodistribution, drug molecule cytotoxicity, tissue damage, quick clearance from the circulation system, solubility and stability of drug molecules. To overcome the limitations of drug delivery, biomaterials have to be developed and applied to drug delivery to protect the drug molecules and to enhance the drug’s efficacy. Protein-based nanomedicine platforms for drug delivery are platforms comprised of naturally self-assembled protein subunits of the same protein or a combination of proteins making up a complete system. They aremore » ideal for drug delivery platforms due to their biocompatibility and biodegradability coupled with low toxicity. A variety of proteins have been used and characterized for drug delivery systems including the ferritin/apoferritin protein cage, plant derived viral capsids, the small Heat shock protein (sHsp) cage, albumin, soy and whey protein, collagen, and gelatin. There are many different types and shapes that have been prepared to deliver drug molecules using protein-based platforms including the various protein cages, microspheres, nanoparticles, hydrogels, films, minirods and minipellets. There are over 30 therapeutic compounds that have been investigated with protein-based drug delivery platforms for the potential treatment of various cancers, infectious diseases, chronic diseases, autoimmune diseases. In protein-based drug delivery platforms, protein cage is the most newly developed biomaterials for drug delivery and therapeutic applications. Their uniform sizes, multifunctions, and biodegradability push them to the frontier for drug delivery. In this review, the recent strategic development of drug delivery has been discussed with a special emphasis upon the polymer based, especially protein-based nanomedicine platforms for drug delivery. The advantages and disadvantages are

Microspheres and Nanotechnology for Drug Delivery.

PubMed

Jóhannesson, Gauti; Stefánsson, Einar; Loftsson, Thorsteinn

2016-01-01

Ocular drug delivery to the posterior segment of the eye can be accomplished by invasive drug injections into different tissues of the eye and noninvasive topical treatment. Invasive treatment involves the risks of surgical trauma and infection, and conventional topical treatments are ineffective in delivering drugs to the posterior segment of the eye. In recent years, nanotechnology has become an ever-increasing part of ocular drug delivery. In the following, we briefly review microspheres and nanotechnology for drug delivery to the eye, including different forms of nanotechnology such as nanoparticles, microparticles, liposomes, microemulsions and micromachines. The permeation barriers and anatomical considerations linked to ocular drug delivery are discussed and a theoretical overview on drug delivery through biological membranes is given. Finally, in vitro, in vivo and human studies of x03B3;-cyclodextrin nanoparticle eyedrop suspensions are discussed as an example of nanotechnology used for drug delivery to the eye. © 2016 S. Karger AG, Basel.

Evaluation of Vaginal Drug Levels and Safety of a Locally Administered Glycerol Monolaurate Cream in Rhesus Macaques.

PubMed

Kirtane, Ameya R; Rothenberger, Meghan K; Frieberg, Abby; Nephew, Karla; Schultz-Darken, Nancy; Schmidt, Thomas; Reimann, Thomas; Haase, Ashley T; Panyam, Jayanth

2017-07-01

The human immunodeficiency virus epidemic affects millions of people worldwide. As women are more vulnerable to infection, female-controlled interventions can help control the spread of the disease significantly. Glycerol monolaurate (GML), an inexpensive and safe compound, has been shown to protect against simian immunodeficiency virus infection when applied vaginally. However, on account of its low aqueous solubility, fabrication of high-dose formulations of GML has proven difficult. We describe the development of a vaginal cream that could be loaded with up to 35% GML. Vaginal drug levels and safety of 3 formulations containing increasing concentrations of GML (5%w/w, 15%w/w, and 35%w/w) were tested in rhesus macaques after vaginal administration. GML concentration in the vaginal tissue increased as the drug concentration in the cream increased, with 35% GML cream resulting in tissue concentration of ∼0.5 mg/g, albeit with high interindividual variability. Compared with the vehicle control, none of the GML creams had any significant effect on the vaginal flora and cytokine (macrophage inflammatory protein 3α and interleukin 8) levels, suggesting that high-dose GML formulations do not induce local adverse effects. In summary, we describe the development of a highly loaded vaginal cream of GML, and vaginal drug levels and safety after local administration in macaques. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Protein-Based Drug-Delivery Materials

PubMed Central

Jao, Dave; Xue, Ye; Medina, Jethro; Hu, Xiao

2017-01-01

There is a pressing need for long-term, controlled drug release for sustained treatment of chronic or persistent medical conditions and diseases. Guided drug delivery is difficult because therapeutic compounds need to survive numerous transport barriers and binding targets throughout the body. Nanoscale protein-based polymers are increasingly used for drug and vaccine delivery to cross these biological barriers and through blood circulation to their molecular site of action. Protein-based polymers compared to synthetic polymers have the advantages of good biocompatibility, biodegradability, environmental sustainability, cost effectiveness and availability. This review addresses the sources of protein-based polymers, compares the similarity and differences, and highlights characteristic properties and functionality of these protein materials for sustained and controlled drug release. Targeted drug delivery using highly functional multicomponent protein composites to guide active drugs to the site of interest will also be discussed. A systematical elucidation of drug-delivery efficiency in the case of molecular weight, particle size, shape, morphology, and porosity of materials will then be demonstrated to achieve increased drug absorption. Finally, several important biomedical applications of protein-based materials with drug-delivery function—including bone healing, antibiotic release, wound healing, and corneal regeneration, as well as diabetes, neuroinflammation and cancer treatments—are summarized at the end of this review. PMID:28772877

Protein-Based Drug-Delivery Materials.

PubMed

Jao, Dave; Xue, Ye; Medina, Jethro; Hu, Xiao

2017-05-09

There is a pressing need for long-term, controlled drug release for sustained treatment of chronic or persistent medical conditions and diseases. Guided drug delivery is difficult because therapeutic compounds need to survive numerous transport barriers and binding targets throughout the body. Nanoscale protein-based polymers are increasingly used for drug and vaccine delivery to cross these biological barriers and through blood circulation to their molecular site of action. Protein-based polymers compared to synthetic polymers have the advantages of good biocompatibility, biodegradability, environmental sustainability, cost effectiveness and availability. This review addresses the sources of protein-based polymers, compares the similarity and differences, and highlights characteristic properties and functionality of these protein materials for sustained and controlled drug release. Targeted drug delivery using highly functional multicomponent protein composites to guide active drugs to the site of interest will also be discussed. A systematical elucidation of drug-delivery efficiency in the case of molecular weight, particle size, shape, morphology, and porosity of materials will then be demonstrated to achieve increased drug absorption. Finally, several important biomedical applications of protein-based materials with drug-delivery function-including bone healing, antibiotic release, wound healing, and corneal regeneration, as well as diabetes, neuroinflammation and cancer treatments-are summarized at the end of this review.

Transient swelling behavior and drug delivery from a dissolving film deploying anti-HIV microbicide

NASA Astrophysics Data System (ADS)

Tasoglu, Savas; Katz, David F.; Szeri, Andrew J.

2010-11-01

Despite more than two decades of HIV vaccine research, there is still no efficacious HIV vaccine. Very recently, a research group has shown that a microbicide gel formulation of antiretroviral drug Tenofovir, significantly inhibits HIV transmission to women [1]. However, there is a widespread agreement that more effective and diverse drug delivery vehicles must be developed. In this setting, there is now great interest in developing different delivery vehicles such as vaginal rings, gels, and films. Here, we develop a model for transient fluid uptake and swelling behavior, and subsequent dissolution and drug deployment from a film containing anti-HIV microbicide. In the model, the polymer structural relaxation via water uptake is assumed to follow first order kinetics. In the case of a film loaded with an osmotically active solute, the kinetic equation is modified to account for the osmotic effect. The transport rate of solvent and solute within the matrix is characterized by a diffusion equation. After the matrix is relaxed to a specified concentration of solvent, lubrication theory and convective-diffusive transport are employed for flow of the liquefied matrix and drug dispersion respectively. [1] Karim, et al., Science, 2010.

MEMS: Enabled Drug Delivery Systems.

PubMed

Cobo, Angelica; Sheybani, Roya; Meng, Ellis

2015-05-01

Drug delivery systems play a crucial role in the treatment and management of medical conditions. Microelectromechanical systems (MEMS) technologies have allowed the development of advanced miniaturized devices for medical and biological applications. This Review presents the use of MEMS technologies to produce drug delivery devices detailing the delivery mechanisms, device formats employed, and various biomedical applications. The integration of dosing control systems, examples of commercially available microtechnology-enabled drug delivery devices, remaining challenges, and future outlook are also discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Drug transporters in tissues and cells relevant to sexual transmission of HIV: Implications for drug delivery.

PubMed

Hu, Minlu; Patel, Sravan Kumar; Zhou, Tian; Rohan, Lisa C

2015-12-10

Efflux and uptake transporters of drugs are key regulators of the pharmacokinetics of many antiretroviral drugs. A growing body of literature has revealed the expression and functionality of multiple transporters in female genital tract (FGT), colorectal tissue, and immune cells. Drug transporters could play a significant role in the efficacy of preventative strategies for HIV-1 acquisition. Pre-exposure prophylaxis (PrEP) is a promising strategy, which utilizes topically (vaginally or rectally), orally or other systemically administered antiretroviral drugs to prevent the sexual transmission of HIV to receptive partners. The drug concentration in the receptive mucosal tissues and target immune cells for HIV is critical for PrEP effectiveness. Hence, there is an emerging interest in utilizing transporter information to explain tissue disposition patterns of PrEP drugs, to interpret inter-individual variability in PrEP drug pharmacokinetics and effectiveness, and to improve tissue drug exposure through modulation of the cervicovaginal, colorectal, or immune cell transporters. In this review, the existing literature on transporter expression, functionality and regulation in the transmission-related tissues and cells is summarized. In addition, the relevance of transporter function for drug delivery and strategies that could exploit transporters for increased drug concentration at target locales is discussed. The overall goal is to facilitate an understanding of drug transporters for PrEP optimization. Copyright © 2015 Elsevier B.V. All rights reserved.

Transcutaneous electrical nerve stimulation (TENS) for pain control after vaginal delivery and cesarean section.

PubMed

Kayman-Kose, Seda; Arioz, Dagistan Tolga; Toktas, Hasan; Koken, Gulengul; Kanat-Pektas, Mine; Kose, Mesut; Yilmazer, Mehmet

2014-10-01

The present study aims to determine the efficiency and reliability of transcutaneous electrical nerve stimulation (TENS) in the management of pain related with uterine contractions after vaginal delivery and the pain related with both abdominal incision uterine contractions after cesarean section. A hundred healthy women who underwent cesarean section under general anesthesia were randomly assigned to the placebo group (Group 1) or the TENS group (Group 2), while 100 women who delivered by vaginal route without episiotomy were randomized into the placebo group (Group 3) or the TENS group (Group 4). The patients in Group 2 had statistically lower visual analog scale (VAS) and verbal numerical scale (VNS) scores than the patients in Group 1 (p < 0.001 for both). The patients in Group 4 had statistically lower VAS and VNS scores than the patients in Group 3 (p = 0.022 and p = 0.005, respectively). The analgesic requirement at the eighth hour of cesarean section was significantly lower in the patients who were treated with TENS (p = 0.006). The need for analgesics at the eighth hour of vaginal delivery was statistically similar in the patients who were treated with TENS and the patients who received placebo (p = 0.830). TENS is an effective, reliable, practical and easily available modality of treatment for postpartum pain.

Permeation enhancer strategies in transdermal drug delivery.

PubMed

Marwah, Harneet; Garg, Tarun; Goyal, Amit K; Rath, Goutam

2016-01-01

Today, ∼74% of drugs are taken orally and are not found to be as effective as desired. To improve such characteristics, transdermal drug delivery was brought to existence. This delivery system is capable of transporting the drug or macromolecules painlessly through skin into the blood circulation at fixed rate. Topical administration of therapeutic agents offers many advantages over conventional oral and invasive techniques of drug delivery. Several important advantages of transdermal drug delivery are prevention from hepatic first pass metabolism, enhancement of therapeutic efficiency and maintenance of steady plasma level of the drug. Human skin surface, as a site of drug application for both local and systemic effects, is the most eligible candidate available. New controlled transdermal drug delivery systems (TDDS) technologies (electrically-based, structure-based and velocity-based) have been developed and commercialized for the transdermal delivery of troublesome drugs. This review article covers most of the new active transport technologies involved in enhancing the transdermal permeation via effective drug delivery system.

Successful Pregnancy with a Full-Term Vaginal Delivery One Year After n-Butyl Cyanoacrylate Embolization of a Uterine Arteriovenous Malformation

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCormick, Colleen C.; Kim, Hyun S.

Uterine arteriovenous malformation (AVM) causes significant morbidity with vaginal bleeding. Traditional therapy is a hysterectomy with no potential for future pregnancy. We present a case of successful superselective embolization of uterine AVM using n-butyl cyanoacrylate with subsequent normal term pregnancy and uncomplicated vaginal delivery in 1 year.

Novel approaches to vaginal delivery and safety of microbicides: biopharmaceuticals, nanoparticles, and vaccines.

PubMed

Whaley, Kevin J; Hanes, Justin; Shattock, Robin; Cone, Richard A; Friend, David R

2010-12-01

The HIV-1 epidemic remains unchecked despite existing technology; vaccines and microbicides in development may help reverse the epidemic. Reverse transcriptase inhibitors (RTIs) formulated in gels tenofovir (TFV) and IVRs (dapivirine) are under clinical development. While TFV or similar products may prove successful for HIV-1, alternatives to RTIs may provide additional benefits, e.g., broader STI prevention. Biopharmaceutical agents under development as microbicides include cyanovirin, RANTES analogues, commensals, and Mabs. Cost of manufacturing biopharmaceuticals has been reduced and they can be formulated into tablets, films, and IVRs for vaginal delivery. Nanotechnology offers a novel approach to formulate microbicides potentially leading to uniform epithelial delivery. Delivery through vaginal mucus may be possible by controlling nanoparticle size and surface characteristics. Combining prevention modalities may be the most effective means of preventing STI transmission, importantly, codelivery of microbicides and vaccines has demonstrated. Finally, the safety of microbicide preparations and excipients commonly used can be assessed using a mouse/HSV-2 susceptibility model. Screening of new microbicide candidates and formulation excipients may avoid past issues of enhancing HIV-1 transmission. This article forms part of a special supplement covering several presentations on novel microbicide formulations from the symposium on "Recent Trends in Microbicide Formulations" held on 25 and 26 January 2010, Arlington, VA. Copyright © 2010 Elsevier B.V. All rights reserved.

Preterm Induction of Labor: Predictors of Vaginal Delivery and Labor Curves

PubMed Central

Feghali, Maisa; Timofeev, Julia; Huang, Chun-Chih; Driggers, Rita; Miodovnik, Menachem; Landy, Helain J.; Umans, Jason G.

2014-01-01

Objective To evaluate the labor curves of patients undergoing preterm induction of labor (IOL) and assess possible predictors of vaginal delivery (VD). Study Design Data from the NICHD Consortium on Safe Labor were analyzed. A total of 6,555 women undergoing medically-indicated IOL before 37 weeks gestational age (GA) were included in this analysis. Patients were divided into four groups based on gestational age: A: 24-27+6, B: 28-30+6, C: 31-33+6, and D: 34-36+6 weeks. Pregnant women with a contraindication to VD, IOL at or after 37 weeks and those without data from cervical exam on admission were excluded. ANOVA was used to assess differences between GA groups. Multiple logistic regression was used to assess predictors of VD. A repeated measures analysis was used to determine average labor curves. Results Rates of vaginal live births increased with GA, from 35% (Group A) to 76% (Group D). Parous women [odds ratio (OR)=6.78, 95% confidence interval (CI) 6.38-7.21] and those with a favorable cervix at the start of IOL (OR=2.35, 95% CI 2.23-2.48) were more likely to deliver vaginally. Analysis of labor curves in nulliparous women showed shorter duration of labor with increasing GA; the active phase of labor was, however, similar across all GA. Conclusion The majority of women undergoing medically-indicated preterm IOL between 24 and 36+6 weeks’ GA deliver vaginally. The strongest predictor of VD was parity. Preterm IOL had a limited influence on estimated labor curves across gestational age. PMID:25068566

Predictors of successful external cephalic version and assessment of success for vaginal delivery.

PubMed

Salzer, Liat; Nagar, Ran; Melamed, Nir; Wiznitzer, Arnon; Peled, Yoav; Yogev, Yariv

2015-01-01

To identify predictors of successful external cephalic version (ECV) and to compare delivery outcome between women who had a successful ECV and women with spontaneous vertex presentation. A retrospective cohort study of all women who underwent ECV in a single tertiary medical center between 2007 and 2011. Delivery outcome was compared between women who underwent a trial of vaginal delivery following successful ECV with that of a control group in a 2:1 ratio. Multivariate analysis was used to identify predictors of successful ECV. Overall 287 were eligible for the study group. Of these 130 (45.3%) had a successful ECV. Polyhydramnios was the strongest factor associated with successful ECV (OR=3.1, 95%-CI 1.4-7.2), followed by transverse lie (versus breech presentation, OR=2.6, 95%-CI 1.2-6.7) and a posterior placenta (OR=1.7, 95%-CI 1.1-3.9), while nulliparity was associated with a lower likelihood of successful ECV (OR=0.4, 95%-CI 0.2-0.6). Women who had a successful ECV and underwent a trial of labor were more likely to deliver by operative vaginal delivery (OVD) (OR=1.8, 95%-CI 1.2-3.6), mainly due to a higher rate of prolonged 2nd, but were not at an increased risk for CS (OR=0.9, 95%-CI 0.4-2.4). Counselling to women prior to ECV should address the likelihood of success based on the predicting factors described above, as well as the increased risk for OVD in the case of successful ECV.

Finite element model focused on stress distribution in the levator ani muscle during vaginal delivery.

PubMed

Krofta, Ladislav; Havelková, Linda; Urbánková, Iva; Krčmář, Michal; Hynčík, Luděk; Feyereisl, Jaroslav

2017-02-01

During vaginal delivery, the levator ani muscle (LAM) undergoes severe deformation. This stress can lead to stretch-related LAM injuries. The objective of this study was to develop a sophisticated MRI-based model to simulate changes in the LAM during vaginal delivery. A 3D finite element model of the female pelvic floor and fetal head was developed. The model geometry was based on MRI data from a nulliparous woman and 1-day-old neonate. Material parameters were estimated using uniaxial test data from the literature and by least-square minimization method. The boundary conditions reflected all anatomical constraints and supports. A simulation of vaginal delivery with regard to the cardinal movements of labor was then performed. The mean stress values in the iliococcygeus portion of the LAM during fetal head extension were 4.91-7.93 MPa. The highest stress values were induced in the pubovisceral and puborectal LAM portions (mean 27.46 MPa) at the outset of fetal head extension. The last LAM subdivision engaged in the changes in stress was the posteromedial section of the puborectal muscle. The mean stress values were 16.89 MPa at the end of fetal head extension. The LAM was elongated by nearly 2.5 times from its initial resting position. The cardinal movements of labor significantly affect the subsequent heterogeneous stress distribution in the LAM. The absolute stress values were highest in portions of the muscle that arise from the pubic bone. These areas are at the highest risk for muscle injuries with long-term complications.

Nanobiotechnology-based drug delivery in brain targeting.

PubMed

Dinda, Subas C; Pattnaik, Gurudutta

2013-01-01

Blood brain barrier (BBB) found to act as rate limiting factor in drug delivery to brain in combating the central nervous system (CNS) disorders. Such limiting physiological factors include the reticuloendothelial system and protein opsonization, which present across BBB, play major role in reducing the passage of drug. Several approaches employed to improve the drug delivery across the BBB. Nanoparticles (NP) are the solid colloidal particle ranges from 1 to 1000 nm in size utilized as career for drug delivery. At present NPs are found to play a significant advantage over the other methods of available drug delivery systems to deliver the drug across the BBB. Nanoparticles may be because of its size and functionalization characteristics able to penetrate and facilitate the drug delivery through the barrier. There are number of mechanisms and strategies found to be involved in this process, which are based on the type of nanomaterials used and its combination with therapeutic agents, such materials include liposomes, polymeric nanoparticles and non-viral vectors of nano-sizes for CNS gene therapy, etc. Nanotechnology is expected to reduce the need for invasive procedures for delivery of therapeutics to the CNS. Some devices such as implanted catheters and reservoirs however will still be needed to overcome the problems in effective drug delivery to the CNS. Nanomaterials are found to improve the safety and efficacy level of drug delivery devices in brain targeting. Nanoegineered devices are found to be delivering the drugs at cellular levels through nono-fluidic channels. Different drug delivery systems such as liposomes, microspheres, nanoparticles, nonogels and nonobiocapsules have been used to improve the bioavailability of the drug in the brain, but microchips and biodegradable polymeric nanoparticulate careers are found to be more effective therapeutically in treating brain tumor. The physiological approaches also utilized to improve the transcytosis capacity

Microprocessor controlled transdermal drug delivery.

PubMed

Subramony, J Anand; Sharma, Ashutosh; Phipps, J B

2006-07-06

Transdermal drug delivery via iontophoresis is reviewed with special focus on the delivery of lidocaine for local anesthesia and fentanyl for patient controlled acute therapy such as postoperative pain. The role of the microprocessor controller in achieving dosimetry, alternating/reverse polarity, pre-programmed, and sensor-based delivery is highlighted. Unique features such as the use of tactile signaling, telemetry control, and pulsatile waveforms in iontophoretic drug delivery are described briefly.

Risk Factors for Uterine Atony/Postpartum Hemorrhage Requiring Treatment after Vaginal Delivery

PubMed Central

Wetta, Luisa A; Szychowski, Jeff M; Seals, Ms. Samantha; Mancuso, Melissa S; Biggio, Joseph R; Tita, Alan TN

2013-01-01

Objective To identify risk factors for uterine atony or hemorrhage. Study Design Secondary analysis of a 3-arm double-blind randomized trial of different dose-regimens of oxytocin to prevent uterine atony after vaginal delivery. The primary outcome was uterine atony or hemorrhage requiring treatment. Twenty-one potential risk factors were evaluated. Logistic regression was used to identify independent risk factors using 2 complementary pre-defined model selection strategies. Results Among 1798 women randomized to 10, 40 or 80U prophylactic oxytocin after vaginal delivery, treated uterine atony occurred in 7%. Hispanic (OR 2.1; 95% CI 1.3–3.4) and non-Hispanic whites (OR 1.6; 95% CI 1.0–2.5), preeclampsia (OR 3.2; 95% CI 2.0–4.9) and chorioamnionitis (OR 2.8; 95% CI 1.6–5.0) were consistent independent risk factors. Other risk factors based on the specified selection strategies were obesity, induction/augmentation of labor, twins, hydramnios, anemia, and arrest of descent. Amnioinfusion appeared to be protective against uterine atony (OR 0.53; 95% CI 0.29–0.98). Conclusion Independent risk factors for uterine atony requiring treatment include Hispanic and non-Hispanic white ethnicity, preeclampsia and chorioamnionitis. PMID:23507549

Dislocation of temporo-mandibular joint - an uncommon circumstance of occurrence: vaginal delivery.

PubMed

El Bouazzaoui, Abderrahim; Labib, Smael; Derkaoui, Ali; Adnane Berdai, Mohammed; Bendadi, Azzeddine; Harandou, Mustapha

2010-06-25

Dislocation of temporo-mandibular joint (TMJ) is an infrequent disease but still spectacular. This disease consists of a permanent, to some extent complete disruption of the temporo-mandibular joint. These dislocations often occur in a context of yawning, and less frequently after a burst of laughing or relatively mild facial trauma (slap, punch on the chin). We report a case of TMJ occurring in an uncommon circumstance: vaginal delivery. A woman aged 24-years with no special past medical history; primipara was admitted in the Department of Maternity of the University Hospital Hassan II of Fez for an imminent delivery of a twin pregnancy. Ten minutes after admission, the patient delivered vaginally with episiotomy. She gave birth to twins weighing 2800 g and 2400 g. During labour, and due to efforts of crying, the patient developed a sudden and immediate loss of function of the temporo-mandibular joint, with difficulty of speaking, the mouth permanently opened and with the chin lowered and thrown forward. The examination found an empty glenoid fossa of the temporo-mandibular joint in both sides. The diagnosis of dislocation of the TMJ was established. A CT scan of facial bones was done, objectifying a bilateral dislocation of TMJ. The reduction of this dislocation was performed in the operating room under sedation.

Rehospitalizations and outpatient contacts of mothers and neonates after hospital discharge after vaginal delivery.

PubMed

Meikle, S F; Lyons, E; Hulac, P; Orleans, M

1998-07-01

Our purpose was to determine whether length of hospital stay after vaginal delivery as determined by the discharging physician is associated with rehospitalizations or increased outpatient contacts by mothers and neonates and to assess the impact of home health care visits. An inception cohort study of all rehospitalizations and outpatient contacts of mothers and neonates after vaginal delivery at St. Joseph Hospital, Denver, Colorado, was done from January 1, 1994, to September 30, 1995. All Kaiser Permanente mother-neonate pairs in which the delivery was vaginal (excluding those with multiple gestations or birth weight < 2500 g) were included. Length of initial hospital stay was divided into three time periods: < or = 24 hours, 25 to 48 hours, and > 48 hours. The Colorado Kaiser Permanente Perinatal Database was used to identify perinatal and demographic factors that might have increased health care use. Additional information was sought in administrative databases, bill records, and inpatient charts. Mothers were followed up for 6 weeks and neonates for 28 days after delivery. Home care visits were provided to more than half the mothers and neonates by means of a standardized protocol. The main outcome measures were rehospitalizations and outpatient visits for mothers and neonate, controlling for home care visits. A total of 4323 mother-neonate pairs were identified. For the mothers, a longer initial hospital stay (> 48 hours) was significantly associated with both readmission (P < .01) and increased outpatient care use (P = .01) in the 6-week postpartum period. Thirty-five mothers (.81%) were rehospitalized by 6 weeks. Maternal factors associated with increased outpatient contacts were preeclampsia, preterm delivery, and instrument delivery. Sixty-seven neonates (1.55%) were readmitted to the hospital. Home care visits reduced the need for both readmissions and outpatient visits. For mothers in this cohort a longer initial hospital stay was significantly

Ultrasound-enhanced drug delivery for cancer.

PubMed

Mo, Steven; Coussios, Constantin-C; Seymour, Len; Carlisle, Robert

2012-12-01

Ultrasound, which has traditionally been used as a diagnostic tool, is increasingly being used in non-invasive therapy and drug delivery. Of particular interest to this review is the rapidly accumulating evidence that ultrasound may have a key role to play both in improving the targeting and the efficacy of drug delivery for cancer. Currently available ultrasound-triggerable vehicles are first described, with particular reference to the ultrasonic mechanism that can activate release and the suitability of the size range of the vehicle used for drug delivery. Further mechanical and thermal effects of ultrasound that can enhance extravasation and drug distribution following release are then critically reviewed. Acoustic cavitation is found to play a potentially key role both in achieving targeted drug release and enhanced extravasation at modest pressure amplitudes and acoustic energies, whilst simultaneously enabling real-time monitoring of the drug delivery process. The next challenge in ultrasound-enhanced drug delivery will thus be to develop a new generation of drug-carrying nanoparticles which are of the right size range for delivery to tumours, yet still capable of achieving initiation of cavitation activity and drug release at modest acoustic pressures and energies that have no safety implications for the patient.

Comparative Study of Oral and Vaginal Misoprostol for Induction of Labour, Maternal and Foetal Outcome

PubMed Central

Komala, Kambhampati; Reddy, Meherlatha; Quadri, Iqbal Jehan; B., Suneetha; V., Ramya

2013-01-01

Background: Misoprostol is a new promising agent for cervical ripening and induction of labour .The ideal dose, route and frequency of administration of misoprostol are still under investigation. Although, vaginal application of misoprostol has been validated as a reasonable mean of induction, there is a patient resistance to digital examination and there is a risk of ascending infection. For this reason, oral administration of misoprostol for cervical ripening and labour induction has been tried. Aims and Objectives: To compare 50μg of oral misoprostol versus 25μg of intravaginal misoprostol for induction of labour at term and maternal, foetal outcomes. Methods: Two hundred women who were at term, with indication for induction of labour and Bishop scores of ≤5 were randomly assigned to receive misoprostol 50μg or 25μg intravaginal, every 4-6 hours, for a maximum of 5 doses. In either group, pregnant females with inadequate uterine contractions despite being given maximum 5 doses of misoprostol, were augmented using oxytocin. The primary outcome measure was time-interval from induction to vaginal delivery and vaginal delivery rate within 24 hours. Results: The median induction to vaginal delivery time in oral group (12.92h) and vaginal group (14.04 h) was not significant. Oral misoprostol resulted in more number of vaginal deliveries as compared to vaginal misoprostol (94% as compared to 86%), which was not significant. There was a significantly higher incidence of uterine tachysystole in the vaginal group, as compared to oral group. There were no significant differences between the groups with respect to oxytocin augmentation, caesarean section rate, analgesic requirement and neonatal outcome. Conclusion: Oral misoprostol is as efficacious as vaginal misoprostol because of shorter induction delivery interval, lower caesarean section rates, and lower incidence of failed induction rates. Lower incidence of foetal distress and easy intake are observed if the

Vaginal delivery after Misgav-Ladach cesarean section--is the risk of uterine rupture acceptable?

PubMed

Hudić, Igor; Fatusić, Zlatan; Kamerić, Lejla; Misić, Mladen; Serak, Indira; Latifagić, Anela

2010-10-01

To evaluate whether the single-layer closure as is a routine by the Misgav-Ladach method compared to the double-layer closure as used by the Dörfler cesarean method is associated with an increased risk of uterine rupture in the subsequent pregnancy and delivery. The analysis is retrospective and is based on medical documentation of the Clinic for Gynecology and Obstetrics, University Clinical Centre, Tuzla, Bosnia and Herzegovina. All patients with one previous cesarean section who attempted vaginal birth following cesarean section were managed from 1 January 2002 to 31 December 2008. Exclusion criteria included multiple gestation, greater than one previous cesarean section, previous incision other than low transverse, gestational age at delivery less than 37 weeks and induction of delivery. We identified 448 patients who met inclusion criteria. We found that 303 patients had a single-layer closure (Misgav-Ladach) and 145 had a double-layer closure (Dörffler) of the previous uterine incision. There were 35 cases of uterine rupture. Of those patients with previous single-layer closure, 5.28% (16/303) had a uterine rupture compared to 13.11% (19/145) in the double-layer closure group (p<0.05). We have not found that a Misgav-Ladach cesarean section method (single-layer uterine closure) might be more likely to result in uterine rupture in women who attempted a vaginal birth after a previous cesarean delivery. This cesarean section method should find its confirmation in everyday clinical practice.

Drug Delivery to CNS: Challenges and Opportunities with Emphasis on Biomaterials Based Drug Delivery Strategies.

PubMed

Khambhla, Ekta; Shah, Viral; Baviskar, Kalpesh

2016-01-01

The current epoch has witnessed a lifestyle impregnated with stress, which is a major cause of several neurological disorders. High morbidity and mortality rate due to neurological diseases and disorders have generated a huge social impact. Despite voluminous research, patients suffering from fatal and/or debilitating CNS diseases such as brain tumors, HIV, encephalopathy, Alzheimer's, epilepsy, Parkinson's, migraine and multiple sclerosis outnumbered those suffering from systemic cancer or heart diseases. The brain being a highly sensitive neuronal organ, has evolved with vasculature barriers, which regulates the efflux and influx of substances to CNS. Treatment of CNS diseases/disorders is challenging because of physiologic, metabolic and biochemical obstacles created by these barriers which comprise mainly of BBB and BCFB. The inability of achieving therapeutically active concentration has become the bottleneck level difficulty, hampering the therapeutic efficiency of several promising drug candidates for CNS related disorders. Parallel maturation of an effective CNS drug delivery strategy with CNS drug discovery is the need of the hour. Recently, the focus of the pharmaceutical community has aggravated in the direction of developing novel and more efficient drug delivery systems, giving the potential of more effective and safer CNS therapies. The present review outlines several hurdles in drug delivery to the CNS along with ideal physicochemical properties desired in drug substance/formulation for CNS delivery. The review also focuses on different conventional and novel strategies for drug delivery to the CNS. The article also assesses and emphasizes on possible benefits of biomaterial based formulations for drug delivery to the CNS.

Drug delivery across length scales.

PubMed

Delcassian, Derfogail; Patel, Asha K; Cortinas, Abel B; Langer, Robert

2018-02-20

Over the last century, there has been a dramatic change in the nature of therapeutic, biologically active molecules available to treat disease. Therapies have evolved from extracted natural products towards rationally designed biomolecules, including small molecules, engineered proteins and nucleic acids. The use of potent drugs which target specific organs, cells or biochemical pathways, necessitates new tools which can enable controlled delivery and dosing of these therapeutics to their biological targets. Here, we review the miniaturisation of drug delivery systems from the macro to nano-scale, focussing on controlled dosing and controlled targeting as two key parameters in drug delivery device design. We describe how the miniaturisation of these devices enables the move from repeated, systemic dosing, to on-demand, targeted delivery of therapeutic drugs and highlight areas of focus for the future.

Polypeptides and polyaminoacids in drug delivery.

PubMed

González-Aramundiz, José Vicente; Lozano, María Victoria; Sousa-Herves, Ana; Fernandez-Megia, Eduardo; Csaba, Noemi

2012-02-01

Advances achieved over the last few years in drug delivery have provided novel and versatile possibilities for the treatment of various diseases. Among the biomaterials applied in this field, it is worth highlighting the increasing importance of polyaminoacids and polypeptides. The appealing properties of these polymers are very promising for the design of novel compositions in a variety of drug delivery applications. This review provides an overview on the general characteristics of polyaminoacids and polypeptides and briefly discusses different synthetic pathways for their production. This is followed by a detailed description of different drug delivery applications of these polymers, emphasizing those examples that already reached advanced preclinical development or have entered clinical trials. Polyaminoacids and polypeptides are gaining much attention in drug delivery due to their exceptional properties. Their application as polymers for drug delivery purposes has been sped up by the significant achievements related to their synthesis. Certainly, cancer therapy has benefited the most from these advances, although other fields such as vaccine delivery and alternative administration routes are also being successfully explored. The design of new entities based on polyaminoacids and polypeptides and the improved insight gained in drug delivery guarantee exciting findings in the near future.

High-intensity focused ultrasound treatment of placenta accreta after vaginal delivery: a preliminary study.

PubMed

Bai, Y; Luo, X; Li, Q; Yin, N; Fu, X; Zhang, H; Qi, H

2016-04-01

To evaluate the safety and efficiency of high-intensity focused ultrasound (HIFU) in the treatment of placenta accreta after vaginal delivery. Enrolled into this study between September 2011 and September 2013 were 12 patients who had been diagnosed with placenta accreta following vaginal delivery and who had stable vital signs. All patients were treated using an ultrasound-guided HIFU treatment system. As indication of the effectiveness of the treatment we considered decreased vascular index on color Doppler imaging, decrease in size of residual placenta compared with pretreatment size on assessment by three-dimensional ultrasound with Virtual Organ Computer-aided Analysis, reduced signal intensity and degree of enhancement on magnetic resonance imaging and avoidance of hysterectomy following treatment. To assess the safety of HIFU treatment, we recorded side effects, hemorrhage, infection, sex steroid levels, return of menses and subsequent pregnancy. Patients were followed up in this preliminary study until December 2013. The 12 patients receiving HIFU treatment had an average postpartum hospital stay of 6.8 days and an average period of residual placental involution of 36.9 days. HIFU treatment did not apparently increase the risk of infection or hemorrhage and no patient required hysterectomy. In all patients menstruation recommenced after an average of 80.2 days, and sex steroid levels during the middle luteal phase of the second menstrual cycle were normal. Two patients became pregnant again during the follow-up period. This preliminary study suggests that ultrasound-guided HIFU is a safe and effective non-invasive method to treat placenta accreta patients after vaginal delivery who have stable vital signs and desire to preserve fertility. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Drug Delivery in Cancer Therapy, Quo Vadis?

PubMed

Lu, Zheng-Rong; Qiao, Peter

2018-03-22

The treatment of malignancies has undergone dramatic changes in the past few decades. Advances in drug delivery techniques and nanotechnology have allowed for new formulations of old drugs, so as to improve the pharmacokinetics, to enhance accumulation in solid tumors, and to reduce the significant toxic effects of these important therapeutic agents. Here, we review the published clinical data in cancer therapy of several major drug delivery systems, including targeted radionuclide therapy, antibody-drug conjugates, liposomes, polymer-drug conjugates, polymer implants, micelles, and nanoparticles. The clinical outcomes of these delivery systems from various phases of clinical trials are summarized. The success and limitations of the drug delivery strategies are discussed based on the clinical observations. In addition, the challenges in applying drug delivery for efficacious cancer therapy, including physical barriers, tumor heterogeneity, drug resistance, and metastasis, are discussed along with future perspectives of drug delivery in cancer therapy. In doing so, we intend to underscore that efficient delivery of cancer therapeutics to solid malignancies remains a major challenge in cancer therapy, and requires a multidisciplinary approach that integrates knowledge from the diverse fields of chemistry, biology, engineering, and medicine. The overall objective of this review is to improve our understanding of the clinical fate of commonly investigated drug delivery strategies, and to identify the limitations that must be addressed in future drug delivery strategies, toward the pursuit of curative therapies for cancer.

Pelvic floor dysfunction in the immediate puerperium, and 1 month and 3 months after vaginal or cesarean delivery.

PubMed

Colla, Cássia; L Paiva, Luciana; Ferla, Lia; B Trento, Maria J; M P de Vargas, Isadora; A Dos Santos, Bianca; Ferreira, Charles F; L Ramos, José G

2018-06-07

To identify and assess postpartum pelvic floor dysfunction (PFD) between vaginal delivery, elective cesarean delivery (ECD), and intrapartum cesarean delivery (ICD). The present prospective observational study included women aged at least 18 years with no history of pelvic surgery or lower urinary tract malformation, and who had not undergone pelvic floor muscle (PFM) training in the preceding 12 months, who underwent delivery at Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil between August 1, 2016, and May 31, 2017. Participants were assessed at 48 hours (phase 1), 1 month (phase 2), and 3 months (phase 3) after delivery. Assessments included the International Consultation on Incontinence Questionnaire, Short Form (ICIQ-SF); the Jorge-Wexner anal incontinence scale; a self-rated visual analog scale for pelvic pain; the pelvic organ prolapse quantification (POP-Q) system; and a PFM perineometer. A total of 227 women were assessed in phase 1 (141 vaginal deliveries; 28 ICDs; and 58 ECDs), 79 in phase 2, and 41 in phase 3. The ICIQ-SF, Jorge-Wexner scale, visual analog scale, and perineometer measurements did not identify significant differences in relation to the type of delivery (P>0.05). The type of delivery was not associated with differences in the short-term development of postpartum PFD. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Smart Polymers in Nasal Drug Delivery

PubMed Central

Chonkar, Ankita; Nayak, Usha; Udupa, N.

2015-01-01

Nasal drug delivery has now been recognized as a promising route for drug delivery due to its capability of transporting a drug to systemic circulation and central nervous system. Though nasal mucosa offers improved bioavailability and quick onset of action of the drug, main disadvantage associated with nasal drug delivery is mucocilliary clearance due to which drug particles get cleared from the nose before complete absorption through nasal mucosa. Therefore, mucoadhesive polymeric approach can be successfully used to enhance the retention of the drug on nasal mucosal surface. Here, some of the aspects of the stimuli responsive polymers have been discussed which possess liquid state at the room temperature and in response to nasal temperature, pH and ions present in mucous, can undergo in situ gelation in nasal cavity. In this review, several temperature responsive, pH responsive and ion responsive polymers used in nasal delivery, their gelling mechanisms have been discussed. Smart polymers not only able to enhance the retention of the drug in nasal cavity but also provide controlled release, ease of administration, enhanced permeation of the drug and protection of the drug from mucosal enzymes. Thus smart polymeric approach can be effectively used for nasal delivery of peptide drugs, central nervous system dugs and hormones. PMID:26664051

Ion-Responsive Drug Delivery Systems.

PubMed

Yoshida, Takayuki; Shakushiro, Kohsuke; Sako, Kazuhiro

2018-02-08

Some kinds of cations and anions are contained in body fluids such as blood, interstitial fluid, gastrointestinal juice, and tears at relatively high concentration. Ionresponsive drug delivery is available to design the unique dosage formulations which provide optimized drug therapy with effective, safe and convenient dosing of drugs. The objective of the present review was to collect, summarize, and categorize recent research findings on ion-responsive drug delivery systems. Ions in body fluid/formulations caused structural changes of polymers/molecules contained in the formulations, allow formulations exhibit functions. The polymers/molecules responding to ions were ion-exchange resins/fibers, anionic or cationic polymers, polymers exhibiting transition at lower critical solution temperature, self-assemble supramolecular systems, peptides, and metalorganic frameworks. The functions of ion-responsive drug delivery systems were categorized to controlled drug release, site-specific drug release, in situ gelation, prolonged retention at the target sites, and enhancement of drug permeation. Administration of the formulations via oral, ophthalmic, transdermal, and nasal routes has showed significant advantages in the recent literatures. Many kinds of drug delivery systems responding to ions have been reported recently for several administration routes. Improvement and advancement of these systems can maximize drugs potential and contribute to patients in the world. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Nanocarriers for cancer-targeted drug delivery.

PubMed

Kumari, Preeti; Ghosh, Balaram; Biswas, Swati

2016-01-01

Nanoparticles as drug delivery system have received much attention in recent years, especially for cancer treatment. In addition to improving the pharmacokinetics of the loaded poorly soluble hydrophobic drugs by solubilizing them in the hydrophobic compartments, nanoparticles allowed cancer specific drug delivery by inherent passive targeting phenomena and adopted active targeting strategies. For this reason, nanoparticles-drug formulations are capable of enhancing the safety, pharmacokinetic profiles and bioavailability of the administered drugs leading to improved therapeutic efficacy compared to conventional therapy. The focus of this review is to provide an overview of various nanoparticle formulations in both research and clinical applications with a focus on various chemotherapeutic drug delivery systems for the treatment of cancer. The use of various nanoparticles, including liposomes, polymeric nanoparticles, dendrimers, magnetic and other inorganic nanoparticles for targeted drug delivery in cancer is detailed.

Colloidal drug delivery system: amplify the ocular delivery.

PubMed

Ali, Javed; Fazil, Mohd; Qumbar, Mohd; Khan, Nazia; Ali, Asgar

2016-01-01

The ocular perceivers are the most voluntarily accessible organs in terms of location in the body, yet drug distribution to these tissues is one of the most intriguing and challenging endeavors and problematic to the pharmaceutical scientist. The most of ocular diseases are treated with topical application of conventional formulation, i.e. solutions, suspensions and ointment. Typically on installation of these conventional formulations, only <5% of the applied dose penetrates the cornea and reaches intraocular tissues, while a major fraction of the instilled dose is wastage due to the presence of many ocular barriers like external barriers, rapid loss of the instilled solution from the precorneal area and nasolacrimal drainage system. Systemic absorption caused systemic side effects varying from mild to life-threatening events. The main objective of this review is to explore the role of colloidal delivery of drug to minimize the drawbacks associated with them. This review provides an insight into the various constraints associated with ocular drug delivery, summarizes recent findings and applications of colloidal delivery systems, i.e. nanoparticles, nanosuspensions, liposomes, niosomes, dendrimers and contact lenses containing nanoparticles have the capacity to distribute ocular drugs to categorical target sites and hold promise to revolutionize the therapy of many ocular perceiver diseases and minimized the circumscription of conventional delivery. Form the basis of literature review, it has been found that the novel delivery system have greater impact to maximize ocular drug absorption, and minimize systemic absorption and side effects.

Ultrasound mediated transdermal drug delivery.

PubMed

Azagury, Aharon; Khoury, Luai; Enden, Giora; Kost, Joseph

2014-06-01

Transdermal drug delivery offers an attractive alternative to the conventional drug delivery methods of oral administration and injections. However, the stratum corneum serves as a barrier that limits the penetration of substances to the skin. Application of ultrasound (US) irradiation to the skin increases its permeability (sonophoresis) and enables the delivery of various substances into and through the skin. This review presents the main findings in the field of sonophoresis in transdermal drug delivery as well as transdermal monitoring and the mathematical models associated with this field. Particular attention is paid to the proposed enhancement mechanisms and future trends in the fields of cutaneous vaccination and gene therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

Vaginal Microbiomes Associated With Aerobic Vaginitis and Bacterial Vaginosis.

PubMed

Kaambo, Evelyn; Africa, Charlene; Chambuso, Ramadhani; Passmore, Jo-Ann Shelley

2018-01-01

A healthy vaginal microbiota is considered to be significant for maintaining vaginal health and preventing infections. However, certain vaginal bacterial commensal species serve an important first line of defense of the body. Any disruption of this microbial barrier might result in a number of urogenital conditions including aerobic vaginitis (AV) and bacterial vaginosis (BV). The health of the vagina is closely associated with inhabitant microbiota. Furthermore, these microbes maintain a low vaginal pH, prevent the acquisition of pathogens, stimulate or moderate the local innate immune system, and further protect against complications during pregnancies. Therefore, this review will focus on vaginal microbial "health" in the lower reproductive tract of women and on the physiological characteristics that determine the well-being of reproductive health. In addition, we explore the distinct versus shared characteristics of BV and AV, which are commonly associated with increased risk for preterm delivery.

Vaginal Microbiomes Associated With Aerobic Vaginitis and Bacterial Vaginosis

PubMed Central

Kaambo, Evelyn; Africa, Charlene; Chambuso, Ramadhani; Passmore, Jo-Ann Shelley

2018-01-01

A healthy vaginal microbiota is considered to be significant for maintaining vaginal health and preventing infections. However, certain vaginal bacterial commensal species serve an important first line of defense of the body. Any disruption of this microbial barrier might result in a number of urogenital conditions including aerobic vaginitis (AV) and bacterial vaginosis (BV). The health of the vagina is closely associated with inhabitant microbiota. Furthermore, these microbes maintain a low vaginal pH, prevent the acquisition of pathogens, stimulate or moderate the local innate immune system, and further protect against complications during pregnancies. Therefore, this review will focus on vaginal microbial “health” in the lower reproductive tract of women and on the physiological characteristics that determine the well-being of reproductive health. In addition, we explore the distinct versus shared characteristics of BV and AV, which are commonly associated with increased risk for preterm delivery. PMID:29632854

Ultrasound-guided drug delivery in cancer

PubMed Central

2017-01-01

Recent advancements in ultrasound and microbubble (USMB) mediated drug delivery technology has shown that this approach can improve spatially confined delivery of drugs and genes to target tissues while reducing systemic dose and toxicity. The mechanism behind enhanced delivery of therapeutics is sonoporation, the formation of openings in the vasculature, induced by ultrasound-triggered oscillations and destruction of microbubbles. In this review, progress and challenges of USMB mediated drug delivery are summarized, with special focus on cancer therapy. PMID:28607323

21 CFR 884.5920 - Vaginal insufflator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Vaginal insufflator. 884.5920 Section 884.5920 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... § 884.5920 Vaginal insufflator. (a) Identification. A vaginal insufflator is a device used to treat...

Limited Efficiency of Drug Delivery to Specific Intracellular Organelles Using Subcellularly "Targeted" Drug Delivery Systems.

PubMed

Maity, Amit Ranjan; Stepensky, David

2016-01-04

Many drugs have been designed to act on intracellular targets and to affect intracellular processes inside target cells. For the desired effects to be exerted, these drugs should permeate target cells and reach specific intracellular organelles. This subcellular drug targeting approach has been proposed for enhancement of accumulation of these drugs in target organelles and improved efficiency. This approach is based on drug encapsulation in drug delivery systems (DDSs) and/or their decoration with specific targeting moieties that are intended to enhance the drug/DDS accumulation in the intracellular organelle of interest. During recent years, there has been a constant increase in interest in DDSs targeted to specific intracellular organelles, and many different approaches have been proposed for attaining efficient drug delivery to specific organelles of interest. However, it appears that in many studies insufficient efforts have been devoted to quantitative analysis of the major formulation parameters of the DDSs disposition (efficiency of DDS endocytosis and endosomal escape, intracellular trafficking, and efficiency of DDS delivery to the target organelle) and of the resulting pharmacological effects. Thus, in many cases, claims regarding efficient delivery of drug/DDS to a specific organelle and efficient subcellular targeting appear to be exaggerated. On the basis of the available experimental data, it appears that drugs/DDS decoration with specific targeting residues can affect their intracellular fate and result in preferential drug accumulation within an organelle of interest. However, it is not clear whether these approaches will be efficient in in vivo settings and be translated into preclinical and clinical applications. Studies that quantitatively assess the mechanisms, barriers, and efficiencies of subcellular drug delivery and of the associated toxic effects are required to determine the therapeutic potential of subcellular DDS targeting.

Recent advances in ophthalmic drug delivery

PubMed Central

Kompella, Uday B; Kadam, Rajendra S; Lee, Vincent HL

2011-01-01

Topical ocular drug bioavailability is notoriously poor, in the order of 5% or less. This is a consequence of effective multiple barriers to drug entry, comprising nasolacrimal drainage, epithelial drug transport barriers and clearance from the vasculature in the conjunctiva. While sustained drug delivery to the back of the eye is now feasible with intravitreal implants such as Vitrasert™ (~6 months), Retisert™ (~3 years) and Iluvien™ (~3 years), currently there are no marketed delivery systems for long-term drug delivery to the anterior segment of the eye. The purpose of this article is to summarize the resurgence in interest to prolong and improve drug entry from topical administration. These approaches include mucoadhesives, viscous polymer vehicles, transporter-targeted prodrug design, receptor-targeted functionalized nanoparticles, iontophoresis, punctal plug and contact lens delivery systems. A few of these delivery systems might be useful in treating diseases affecting the back of the eye. Their effectiveness will be compared against intravitreal implants (upper bound of effectiveness) and trans-scleral systems (lower bound of effectiveness). Refining the animal model by incorporating the latest advances in microdialysis and imaging technology is key to expanding the knowledge central to the design, testing and evaluation of the next generation of innovative ocular drug delivery systems. PMID:21399724

Obstetric outcomes of pre-induction of labor with a 200 μg misoprostol vaginal insert.

PubMed

Jagielska, Iwona; Kazdepka-Ziemińska, Anita; Tyloch, Małgorzata; Sopońska-Brzoszczyk, Paulina; Nowak, Karina; Dziedzic, Dawid; Dzikowska, Ewa; Grabiec, Marek

2017-01-01

Labor induction is indicated in 20% to 40% of pregnancies. Over half of pregnancies qualified for the induction of labor require stimulation of the cervix to ripen. The drug used increasingly more often in pre-induction is the PGE-1 pros-taglandin analog - misoprostol 200 μg. The study includes a total of 100 patients qualified for labor pre-induction with Misodel® (miso-prostol 200 μg vaginal insert). The study group comprises two subgroups: primigravidas and multiparas. Assessments included: indications for labor pre-induction, time from Misodel application to delivery, caesarean section rate and indica-tions, duration of first and second stage of labor, rate of vaginal deliveries, need for oxytocin or fenoterol administration side effects and newborn condition. The most common indication for labor induction was gestational diabetes and pregnancy past term. The average time to vaginal delivery was 14 h 45 min, time to the onset of active phase of labor - 11 h 45 min, time to membranes' rupture - 15 h, time to vaginal delivery - 14 h 18 min. The times of multiparas were significantly shorter. The rate of vaginal deliveries within 12 hours amounted to 42.42%, while within 24 hours it reached 83.33%. The overall caesarean section rate was 33%. The most common indication for caesarean section was the risk of intrauterine hypoxia. Tachysystole and hyperstimulation was observed in 4% of cases, while abnormalities in the cardiotocographic tracing in 43%. Misodel is an effective method for labor pre-induction, without affecting the caesarean section rate and has no adverse effect on the newborn condition.

Advancements in ocular drug delivery.

PubMed

Weiner, Alan L; Gilger, Brian C

2010-11-01

This review covers both noninvasive and invasive ophthalmic drug delivery systems that can have application to therapy of veterinary ophthalmic diseases. Noninvasive approaches include gel technologies, permeation enhancement via pro-drug development, solubilization agents and nanoparticle technologies, iontophoresis, microneedles, drug-eluting contact lenses and eye misters, and microdroplets. More invasive systems include both eroding implants and noneroding technologies that encompass diffusion based systems, active pumps, intraocular lenses, suprachoroidal drug delivery, and episcleral reservoirs. In addition to addressing the physiologic challenges of achieving the necessary duration of delivery, tissue targeting and patient compliance, the commercial development factors of biocompatibility, sterilization, manufacturability and long-term stability will be discussed. © 2010 American College of Veterinary Ophthalmologists.

Use of urea and creatinine levels in vaginal fluid for the diagnosis of preterm premature rupture of membranes and delivery interval after membrane rupture.

PubMed

Gezer, Cenk; Ekin, Atalay; Golbasi, Ceren; Kocahakimoglu, Ceysu; Bozkurt, Umit; Dogan, Askin; Solmaz, Ulaş; Golbasi, Hakan; Taner, Cuneyt Eftal

2017-04-01

To determine whether urea and creatinine measurements in vaginal fluid could be used to diagnose preterm premature rupture of membranes (PPROM) and predict delivery interval after PPROM. A prospective study conducted with 100 pregnant women with PPROM and 100 healthy pregnant women between 24 + 0 and 36 + 6 gestational weeks. All patients underwent sampling for urea and creatinine concentrations in vaginal fluid at the time of admission. Receiver operator curve analysis was used to determine the cutoff values for the presence of PPROM and delivery within 48 h after PPROM. In multivariate logistic regression analysis, vaginal fluid urea and creatinine levels were found to be significant predictors of PPROM (p < 0.001 and p < 0.001, respectively) and delivery within 48 h after PPROM (p = 0.012 and p = 0.017, respectively). The optimal cutoff values for the diagnosis of PPROM were >6.7 mg/dl for urea and >0.12 mg/dl for creatinine. The optimal cutoff values for the detection of delivery within 48 h were >19.4 mg/dl for urea and >0.23 mg/dl for creatinine. Measurement of urea and creatinine levels in vaginal fluid is a rapid and reliable test for diagnosing and also for predicting delivery interval after PPROM.

21 CFR 884.3575 - Vaginal pessary.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Vaginal pessary. 884.3575 Section 884.3575 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL... Vaginal pessary. (a) Identification. A vaginal pessary is a removable structure placed in the vagina to...

Smart Drug Delivery Systems in Cancer Therapy.

PubMed

Unsoy, Gozde; Gunduz, Ufuk

2018-02-08

Smart nanocarriers have been designed for tissue-specific targeted drug delivery, sustained or triggered drug release and co-delivery of synergistic drug combinations to develop safer and more efficient therapeutics. Advances in drug delivery systems provide reduced side effects, longer circulation half-life and improved pharmacokinetics. Smart drug delivery systems have been achieved successfully in the case of cancer. These nanocarriers can serve as an intelligent system by considering the differences of tumor microenvironment from healthy tissue, such as low pH, low oxygen level, or high enzymatic activity of matrix metalloproteinases. The performance of anti-cancer agents used in cancer diagnosis and therapy is improved by enhanced cellular internalization of smart nanocarriers and controlled drug release. Here, we review targeting, cellular internalization; controlled drug release and toxicity of smart drug delivery systems. We are also emphasizing the stimulus responsive controlled drug release from smart nanocarriers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Vaginal rings for delivery of HIV microbicides

PubMed Central

Malcolm, R Karl; Fetherston, Susan M; McCoy, Clare F; Boyd, Peter; Major, Ian

2012-01-01

Following the successful development of long-acting steroid-releasing vaginal ring devices for the treatment of menopausal symptoms and contraception, there is now considerable interest in applying similar devices to the controlled release of microbicides against HIV. In this review article, the vaginal ring concept is first considered within the wider context of the early advances in controlled-release technology, before describing the various types of ring device available today. The remainder of the article highlights the key developments in HIV microbicide-releasing vaginal rings, with a particular focus on the dapivirine ring that is presently in late-stage clinical testing. PMID:23204872

Vaginal rings for delivery of HIV microbicides.

PubMed

Malcolm, R Karl; Fetherston, Susan M; McCoy, Clare F; Boyd, Peter; Major, Ian

2012-01-01

Following the successful development of long-acting steroid-releasing vaginal ring devices for the treatment of menopausal symptoms and contraception, there is now considerable interest in applying similar devices to the controlled release of microbicides against HIV. In this review article, the vaginal ring concept is first considered within the wider context of the early advances in controlled-release technology, before describing the various types of ring device available today. The remainder of the article highlights the key developments in HIV microbicide-releasing vaginal rings, with a particular focus on the dapivirine ring that is presently in late-stage clinical testing.

Heterocyclic Drug-polymer Conjugates for Cancer Targeted Drug Delivery.

PubMed

Kaur, Harmeet; Desai, Sapna D; Kumar, Virender; Rathi, Pooja; Singh, Jasbir

2016-01-01

New polymer therapeutics like polymer-drug conjugates (PDCs) are developing day by day. Heterocyclic drugs with excellent cytotoxic properties are available, but lack of their specificity makes them available to the normal cells also, which is the main cause of their toxicity. Drugs in the form of PDCs make delivery possible to the specific sites. Most of the PDCs are designed with the aim to either target and/or to get activated in specific cancer microenvironments. Therefore, the most exploited targets for cancer drug delivery are; cancer cell enzymes, heat shock protein 90 (HSP90), multi-drug resistance (MDR) proteins, angiogenesis, apoptosis and cell membrane receptors (e.g., folates, transferrin, etc.). In this review, we will summarize PDCs of heterocyclic drugs, like doxorubicin (DOX), daunorubicin, paclitaxel (PTX), docetaxel (DTX), cisplatin, camptothecin (CPT), geldanamycin (GDM), etc., and some of their analogs for efficient delivery of drugs to cancer cells.

Preterm induction of labor: predictors of vaginal delivery and labor curves.

PubMed

Feghali, Maisa; Timofeev, Julia; Huang, Chun-Chih; Driggers, Rita; Miodovnik, Menachem; Landy, Helain J; Umans, Jason G

2015-01-01

The purpose of this study was to evaluate the labor curves of patients who undergo preterm induction of labor (IOL) and to assess possible predictors of vaginal delivery (VD). Data from the National Institute of Child Health and Human Development Consortium on Safe Labor were analyzed. A total of 6555 women who underwent medically indicated IOL at <37 weeks of gestation were included in this analysis. Patients were divided into 4 groups based on gestational age (GA): group A, 24-27+6 weeks; B, 28-30+6 weeks; C, 31-33+6 weeks; and D, 34-36+6 weeks. Pregnant women with a contraindication to VD, IOL ≥37 weeks of gestation, and without data from cervical examination on admission were excluded. Analysis of variance was used to assess differences between GA groups. Multiple logistic regression was used to assess predictors of VD. A repeated measures analysis was used to determine average labor curves. Rates of vaginal live births increased with GA, from 35% (group A) to 76% (group D). Parous women (odds ratio, 6.78; 95% confidence interval, 6.38-7.21) and those with a favorable cervix at the start of IOL (odds ratio, 2.35; 95% confidence interval, 2.23-2.48) were more likely to deliver vaginally. Analysis of labor curves in nulliparous women showed shorter duration of labor with increasing GA; the active phase of labor was, however, similar across all GAs. Most women who undergo medically indicated preterm IOL between 24 and 36+6 weeks of gestation deliver vaginally. The strongest predictor of VD was parity. Preterm IOL had a limited influence on estimated labor curves across GAs. Copyright © 2015 Elsevier Inc. All rights reserved.

Photomechanical drug delivery

NASA Astrophysics Data System (ADS)

Doukas, Apostolos G.; Lee, Shun

2000-05-01

Photomechanical waves (PW) are generated by Q-switched or mode-locked lasers. Ablation is a reliable method for generating PWs with consistent characteristics. Depending on the laser wavelength and target material, PWs with different parameters can be generated which allows the investigation of PWs with cells and tissue. PWs have been shown to permeabilize the stratum corneum (SC) in vivo and facilitate the transport of drugs into the skin. Once a drug has diffused into the dermis it can enter the vasculature, thus producing a systemic effect. Fluorescence microscopy of biopsies show that 40-kDa molecules can be delivered to a depth of > 300 micrometers into the viable skin of rats. Many important drugs such as insulin, and erythropoietin are smaller or comparable in size, making the PWs attractive for transdermal drug delivery. There are three possible pathways through the SC: Transappendageal via hair follicles or other appendages, transcellular through the corneocytes, and intercellular via the extracellular matrix. The intracellular route appears to be the most likely pathway of drug delivery through the SC.

Recent advances in oral pulsatile drug delivery.

PubMed

Kalantzi, Lida E; Karavas, Evangelos; Koutris, Efthimios X; Bikiaris, Dimitrios N

2009-01-01

Pulsatile drug delivery aims to release drugs on a programmed pattern i.e.: at appropriate time and/or at appropriate site of action. Currently, it is gaining increasing attention as it offers a more sophisticated approach to the traditional sustained drug delivery i.e: a constant amount of drug released per unit time or constant blood levels. Technically, pulsatile drug delivery systems administered via the oral route could be divided into two distinct types, the time controlled delivery systems and the site-specific delivery systems. The simplest pulsatile formulation is a two layer press coated tablet consisted of polymers with different dissolution rates. Homogenicity of the coated barrier is mandatory in order to assure the predictability of the lag time. The disadvantage of such formulation is that the rupture time cannot be always adequately manipulated as it is strongly correlated with the physicochemical properties of the polymer. Gastric retentive systems, systems where the drug is released following a programmed lag phase, chronopharmaceutical drug delivery systems matching human circadian rhythms, multiunit or multilayer systems with various combinations of immediate and sustained-release preparation, are all classified under pulsatile drug delivery systems. On the other hand, site-controlled release is usually controlled by factors such as the pH of the target site, the enzymes present in the intestinal tract and the transit time/pressure of various parts of the intestine. In this review, recent patents on pulsatile drug delivery of oral dosage forms are summarized and discussed.

Nanomaterials in cancer-therapy drug delivery system.

PubMed

Zhang, Gen; Zeng, Xin; Li, Ping

2013-05-01

Nanomaterials can enhance the delivery and treatment efficiency of anti-cancer drugs, and the mechanisms of the tumor-reducing activity of nanomaterials with cancer drug have been investigated. The task for drug to reach pathological areas has facilitated rapid advances in nanomedicine. Herein, we summarize promising findings with respect to cancer therapeutics based on nano-drug delivery vectors. Relatively high toxicity of uncoated nanoparticles restricts the use of these materials in humans. In order to reduce toxicity, many approaches have focused on the encapsulation of nanoparticles with biocompatible materials. Efficient delivery systems have been developed that utilized nanoparticles loaded with high dose of cancer drug in the presence of bilayer molecules. Well-established nanotechnologies have been designed for drug delivery with specific bonding. Surface-modified nanoparticles as vehicles for drug delivery system that contains multiple nano-components, each specially designed to achieve aimed task for the emerging application delivery of therapeutics. Drug-coated polymer nanoparticles could efficiently increase the intracellular accumulation of anti-cancer drugs. This review also introduces the nanomaterials with drug on the induction of apoptosis in cancer cells in vitro and in vivo. Direct interactions between the particles and cellular molecules to cause adverse biological responses are also discussed.

Failed manual removal of the placenta after vaginal delivery.

PubMed

Bjurström, Johanna; Collins, Sally; Langhoff-Roos, Jens; Sundberg, Karin; Jørgensen, Annemette; Duvekot, Johannes J; Groenbeck, Lene

2018-02-01

A retained placenta after vaginal delivery where manual removal of placenta fails is a clinical challenge. We present six cases that illustrate the heterogeneity of the condition and discuss the etiology and terminology as well as the clinical management. Members of the European Working group on Abnormally Invasive Placenta (EW-AIP) were invited to report all recent cases of retained placenta that were not antenatally suspected to be abnormally adherent or invasive, but could not be removed manually despite several attempts. The six cases from Denmark, The Netherlands and the UK provide examples of various treatment strategies such as ultrasound-guided vaginal removal, removal of the placenta through a hysterotomy and just leaving the placenta in situ. The placentas were all retained, but it was only possible to diagnose abnormal invasion in the one case, which had a histopathological diagnosis of increta. Based on these cases we present a flow chart to aid clinical management for future cases. We need properly defined stringent terminology for the different types of retained placenta, as well as improved tools to predict and diagnose both abnormally invasive and abnormally adherent placenta. Clinicians need to be aware of the options available to them when confronted by the rare case of a retained placenta that cannot be removed manually in a hemodynamically stable patient.

Nanomedicine Drug Delivery across Mucous Membranes

NASA Astrophysics Data System (ADS)

Lancina, Michael George, III

Control over the distribution of therapeutic compounds is a complex and somewhat overlooked field of pharmaceutical research. When swallowing a pill or receiving an injection, it is commonly assumed that drug will spread throughout the body in a more or less uniform concentration and find its way to wherever it is needed. In truth, drug biodistribuition is highly non-uniform and dependent on a large number of factors. The development of advanced drug delivery systems to control biodistribution can produce significant advances in clinical treatments without the need to discover new therapeutic compounds. This work focuses on a number of nanostructured materials designed to improve drug delivery by direct and efficient transfer of drugs across one of the body's external mucous membranes. Chapter 1 outlines the central concept that unites these studies: nanomaterials and cationic particles can be used to delivery therapeutic compounds across mucous membranes. Special attention is given to dendritic nanoparticles. In chapter 2, uses for dendrimers in ocular drug delivery are presented. The studies are divided into two main groups: topical and injectable formulations. Chapter 3 does not involve dendrimers but instead another cationic particle used in transmembrane drug delivery, chitosan. Next, a dendrimer based nanofiber mat was used to deliver anti-glaucoma drugs in chapter 4. A three week in vivo efficacy trial showed dendrimer nanofiber mats outperformed traditional eye drops in terms of intra-ocular pressure decrease in a normotensive rat model. Finally, we have developed a new dendrimer based anti-glaucoma drug in chapter 5. Collectively, these studies demonstrate some of the potential applications for nanotechnology to improve transmembrane drug delivery. These particles and fibers are able to readily adhere and penetrate across epithelial cell lays. Utilizing these materials to improve drug absorption through these portals has the potential to improve the

Solid lipid nanoparticles for ocular drug delivery.

PubMed

Seyfoddin, Ali; Shaw, John; Al-Kassas, Raida

2010-01-01

Ocular drug delivery remains challenging because of the complex nature and structure of the eye. Conventional systems, such as eye drops and ointments, are inefficient, whereas systemic administration requires high doses resulting in significant toxicity. There is a need to develop novel drug delivery carriers capable of increasing ocular bioavailability and decreasing both local and systemic cytotoxicity. Nanotechnology is expected to revolutionize ocular drug delivery. Many nano-structured systems have been employed for ocular drug delivery and yielded some promising results. Solid lipid nanoparticles (SLNs) have been looked at as a potential drug carrier system since the 1990s. SLNs do not show biotoxicity as they are prepared from physiological lipids. SLNs are especially useful in ocular drug delivery as they can enhance the corneal absorption of drugs and improve the ocular bioavailability of both hydrophilic and lipophilic drugs. SLNs have another advantage of allowing autoclave sterilization, a necessary step towards formulation of ocular preparations. This review outlines in detail the various production, characterization, sterilization, and stabilization techniques for SLNs. In-vitro and in-vivo methods to study the drug release profile of SLNs have been explained. Special attention has been given to the nature of lipids and surfactants commonly used for SLN production. A summary of previous studies involving the use of SLNs in ocular drug delivery is provided, along with a critical evaluation of SLNs as a potential ocular delivery system.

Rationale and Safety Assessment of a Novel Intravaginal Drug-Delivery System with Sustained DL-Lactic Acid Release, Intended for Long-Term Protection of the Vaginal Microbiome.

PubMed

Verstraelen, Hans; Vervaet, Chris; Remon, Jean-Paul

2016-01-01

Bacterial vaginosis is a prevalent state of dysbiosis of the vaginal microbiota with wide-ranging impact on human reproductive health. Based on recent insights in community ecology of the vaginal microbiome, we hypothesize that sustained vaginal DL-lactic acid enrichment will enhance the recruitment of lactobacilli, while counteracting bacterial vaginosis-associated bacteria. We therefore aimed to develop an intravaginal device that would be easy to insert and remove, while providing sustained DL-lactic acid release into the vaginal lumen. The final prototype selected is a vaginal ring matrix system consisting of a mixture of ethylene vinyl acetate and methacrylic acid-methyl methacrylate copolymer loaded with 150 mg DL-lactic acid with an L/D-lactic acid ratio of 1:1. Preclinical safety assessment was performed by use of the Slug Mucosal Irritation test, a non-vertebrate assay to evaluate vaginal mucosal irritation, which revealed no irritation. Clinical safety was evaluated in a phase I trial with six healthy nulliparous premenopausal volunteering women, with the investigational drug left in place for 7 days. Colposcopic monitoring according to the WHO/CONRAD guidelines for the evaluation of vaginal products, revealed no visible cervicovaginal mucosal changes. No adverse events related to the investigational product occurred. Total release from the intravaginal ring over 7 days was estimated through high performance liquid chromatography at 37.1 (standard deviation 0.9) mg DL-lactic acid. Semisolid lactic acid formulations have been studied to a limited extent in the past and typically consist of a large volume of excipients and very high doses of lactic acid, which is of major concern to mucosal safety. We have documented the feasability of enriching the vaginal environment with pure DL-lactic acid with a prototype intravaginal ring. Though the efficacy of this platform remains to be established possibly requiring further development, this approach may offer a

Rationale and Safety Assessment of a Novel Intravaginal Drug-Delivery System with Sustained DL-Lactic Acid Release, Intended for Long-Term Protection of the Vaginal Microbiome

PubMed Central

Verstraelen, Hans; Vervaet, Chris; Remon, Jean-Paul

2016-01-01

Bacterial vaginosis is a prevalent state of dysbiosis of the vaginal microbiota with wide-ranging impact on human reproductive health. Based on recent insights in community ecology of the vaginal microbiome, we hypothesize that sustained vaginal DL-lactic acid enrichment will enhance the recruitment of lactobacilli, while counteracting bacterial vaginosis-associated bacteria. We therefore aimed to develop an intravaginal device that would be easy to insert and remove, while providing sustained DL-lactic acid release into the vaginal lumen. The final prototype selected is a vaginal ring matrix system consisting of a mixture of ethylene vinyl acetate and methacrylic acid-methyl methacrylate copolymer loaded with 150 mg DL-lactic acid with an L/D-lactic acid ratio of 1:1. Preclinical safety assessment was performed by use of the Slug Mucosal Irritation test, a non-vertebrate assay to evaluate vaginal mucosal irritation, which revealed no irritation. Clinical safety was evaluated in a phase I trial with six healthy nulliparous premenopausal volunteering women, with the investigational drug left in place for 7 days. Colposcopic monitoring according to the WHO/CONRAD guidelines for the evaluation of vaginal products, revealed no visible cervicovaginal mucosal changes. No adverse events related to the investigational product occurred. Total release from the intravaginal ring over 7 days was estimated through high performance liquid chromatography at 37.1 (standard deviation 0.9) mg DL-lactic acid. Semisolid lactic acid formulations have been studied to a limited extent in the past and typically consist of a large volume of excipients and very high doses of lactic acid, which is of major concern to mucosal safety. We have documented the feasability of enriching the vaginal environment with pure DL-lactic acid with a prototype intravaginal ring. Though the efficacy of this platform remains to be established possibly requiring further development, this approach may offer a

Development of amino acid substituted gemini surfactant-based mucoadhesive gene delivery systems for potential use as noninvasive vaginal genetic vaccination.

PubMed

Singh, Jagbir; Michel, Deborah; Getson, Heather M; Chitanda, Jackson M; Verrall, Ronald E; Badea, Ildiko

2015-02-01

Recently, we synthesized amino acid- and peptide-substituted gemini surfactants, 'biolipids' that exhibited high transfection efficiency in vitro. In this study, we developed these plasmid DNA and gemini surfactant lipid particles for noninvasive administration in vaginal cavity. Novel formulations of these gene delivery systems were prepared with poloxamer 407 to induce in situ gelling of the formulation and diethylene glycol monoethyl ether to improve their penetration across mucosal tissue. Poloxamer at 16% w/v concentration in diethylene glycol monoethyl ether aqueous solution produced dispersions that gelled near body temperature and had a high yield value, preventing leakage of the formulation from the vaginal cavity. Intravaginal administration in rabbits showed that the glycyl-lysine-substituted gemini surfactant led to a higher gene expression compared with the parent unsubstituted gemini surfactant. This provides a proof-of-concept that amino acid substituted gemini surfactants can be used as noninvasive mucosal (vaginal) gene delivery systems to treat diseases associated with mucosal epithelia.

Biomimetics in drug delivery systems: A critical review.

PubMed

Sheikhpour, Mojgan; Barani, Leila; Kasaeian, Alibakhsh

2017-05-10

Today, the advanced drug delivery systems have been focused on targeted drug delivery fields. The novel drug delivery is involved with the improvement of the capacity of drug loading in drug carriers, cellular uptake of drug carriers, and the sustained release of drugs within target cells. In this review, six groups of therapeutic drug carriers including biomimetic hydrogels, biomimetic micelles, biomimetic liposomes, biomimetic dendrimers, biomimetic polymeric carriers and biomimetic nanostructures, are studied. The subject takes advantage of the biomimetic methods of productions or the biomimetic techniques for the surface modifications, similar to what accrues in natural cells. Moreover, the effects of these biomimetic approaches for promoting the drug efficiency in targeted drug delivery are visible. The study demonstrates that the fabrication of biomimetic nanocomposite drug carriers could noticeably promote the efficiency of drugs in targeted drug delivery systems. Copyright © 2017 Elsevier B.V. All rights reserved.

PLGA: a unique polymer for drug delivery.

PubMed

Kapoor, Deepak N; Bhatia, Amit; Kaur, Ripandeep; Sharma, Ruchi; Kaur, Gurvinder; Dhawan, Sanju

2015-01-01

Biodegradable polymers have played an important role in the delivery of drugs in a controlled and targeted manner. Polylactic-co-glycolic acid (PLGA) is one of the extensively researched synthetic biodegradable polymers due to its favorable properties. It is also known as a 'Smart Polymer' due to its stimuli sensitive behavior. A wide range of PLGA-based drug delivery systems have been reported for the treatment or diagnosis of various diseases and disorders. The present review provides an overview of the chemistry, physicochemical properties, biodegradation behavior, evaluation parameters and applications of PLGA in drug delivery. Different drug-polymer combinations developed into drug delivery or carrier systems are enumerated and discussed.

Silk-Based Biomaterials for Sustained Drug Delivery

PubMed Central

Yucel, Tuna; Lovett, Michael L.; Kaplan, David L.

2014-01-01

Silk presents a rare combination of desirable properties for sustained drug delivery, including aqueous-based purification and processing options without chemical cross-linkers, compatibility with common sterilization methods, controllable and surface-mediated biodegradation into non-inflammatory by-products, biocompatibility, utility in drug stabilization, and robust mechanical properties. A versatile silk-based toolkit is currently available for sustained drug delivery formulations of small molecule through macromolecular drugs, with a promise to mitigate several drawbacks associated with other degradable sustained delivery technologies in the market. Silk-based formulations utilize silk’s well-defined nano- through microscale structural hierarchy, stimuli-responsive self-assembly pathways and crystal polymorphism, as well as sequence and genetic modification options towards targeted pharmaceutical outcomes. Furthermore, by manipulating the interactions between silk and drug molecules, near-zero order sustained release may be achieved through diffusion- and degradation-based release mechanisms. Because of these desirable properties, there has been increasing industrial interest in silk-based drug delivery systems currently at various stages of the developmental pipeline from pre-clinical to FDA-approved products. Here, we discuss the unique aspects of silk technology as a sustained drug delivery platform and highlight the current state of the art in silk-based drug delivery. We also offer a potential early development pathway for silk-based sustained delivery products. PMID:24910193

Dendrimers for Drug Delivery.

PubMed

Chauhan, Abhay Singh

2018-04-18

Dendrimers have come a long way in the last 25 years since their inception. Originally created as a wonder molecule of chemistry, dendrimer is now in the fourth class of polymers. Dr. Donald Tomalia first published his seminal work on Poly(amidoamine) (PAMAM) dendrimers in 1985. Application of dendrimers as a drug delivery system started in late 1990s. Dendrimers for drug delivery are employed using two approaches: (i) formulation and (ii) nanoconstruct. In the formulation approach, drugs are physically entrapped in a dendrimer using non-covalent interactions, whereas drugs are covalently coupled on dendrimers in the nanoconstruct approach. We have demonstrated the utility of PAMAM dendrimers for enhancing solubility, stability and oral bioavailability of various drugs. Drug entrapment and drug release from dendrimers can be controlled by modifying dendrimer surfaces and generations. PAMAM dendrimers are also shown to increase transdermal permeation and specific drug targeting. Dendrimer platforms can be engineered to attach targeting ligands and imaging molecules to create a nanodevice. Dendrimer nanotechnology, due to its multifunctional ability, has the potential to create next generation nanodevices.

Porous Inorganic Drug Delivery Systems-a Review.

PubMed

Sayed, E; Haj-Ahmad, R; Ruparelia, K; Arshad, M S; Chang, M-W; Ahmad, Z

2017-07-01

Innovative methods and materials have been developed to overcome limitations associated with current drug delivery systems. Significant developments have led to the use of a variety of materials (as excipients) such as inorganic and metallic structures, marking a transition from conventional polymers. Inorganic materials, especially those possessing significant porosity, are emerging as good candidates for the delivery of a range of drugs (antibiotics, anticancer and anti-inflammatories), providing several advantages in formulation and engineering (encapsulation of drug in amorphous form, controlled delivery and improved targeting). This review focuses on key selected developments in porous drug delivery systems. The review provides a short broad overview of porous polymeric materials for drug delivery before focusing on porous inorganic materials (e.g. Santa Barbara Amorphous (SBA) and Mobil Composition of Matter (MCM)) and their utilisation in drug dosage form development. Methods for their preparation and drug loading thereafter are detailed. Several examples of porous inorganic materials, drugs used and outcomes are discussed providing the reader with an understanding of advances in the field and realistic opportunities.

Preparation and characterization of mucoadhesive nanoparticles of poly (methyl vinyl ether-co-maleic anhydride) containing glycyrrhizic acid intended for vaginal administration.

PubMed

Aguilar-Rosas, Irene; Alcalá-Alcalá, Sergio; Llera-Rojas, Viridiana; Ganem-Rondero, Adriana

2015-01-01

Traditional vaginal preparations reside in the vaginal cavity for relatively a short period of time, requiring multiple doses in order to attain the desired therapeutic effect. Therefore, mucoadhesive systems appear to be appropriate to prolong the residence time in the vaginal cavity. In the current study, mucoadhesive nanoparticles based on poly(methyl vinyl ether-co-maleic anhydride) (PVM/MA) intended for vaginal delivery of glycyrrhizic acid (GA) (a drug with well-known antiviral properties) were prepared and characterized. Nanoparticles were generated by a solvent displacement method. Incorporation of GA was performed during nanoprecipitation, followed by adsorption of drug once nanoparticles were formed. The prepared nanoparticles were characterized in terms of size, Z-potential, morphology, drug loading, interaction of GA with PVM/MA (by differential scanning calorimetry) and the in vitro interaction of nanoparticles with pig mucin (at two pH values, 3.6 and 5; with and without GA adsorbed). The preparation method led to nanoparticles of a mean diameter of 198.5 ± 24.3 nm, zeta potential of -44.8 ± 2.8 mV and drug loading of 15.07 ± 0.86 µg/mg polymer. The highest mucin interaction resulted at pH 3.6 for nanoparticles without GA adsorbed. The data obtained suggest the promise of using mucoadhesive nanoparticles of PVM/MA for intravaginal delivery of GA.

Topical drug delivery systems: a patent review.

PubMed

Singh Malik, Deepinder; Mital, Neeraj; Kaur, Gurpreet

2016-01-01

Topical administration is the favored route for local delivery of therapeutic agents due to its convenience and affordability. The specific challenge of designing a therapeutic system is to achieve an optimal concentration of a certain drug at its site of action for an appropriate duration. This review summarizes innovations from the past 3 years (2012-2015) in the field of topical drug delivery for the treatment of local infections of the vagina, nose, eye and skin. The review also throws some light on the anatomy and physiology of these organs and their various defensive barriers which affect the delivery of drugs administered topically. Topical administration has been gaining attention over the last few years. However, conventional topical drug delivery systems suffer from drawbacks such as poor retention and low bioavailability. The successful formulation of topical delivery products requires the careful manipulation of defensive barriers and selection of a soluble drug carrier. Extensive research is required to develop newer topical drug delivery systems aiming either to improve the efficacy or to reduce side effects compared to current patented systems.

Ultrasound-mediated drug delivery for cardiovascular disease

PubMed Central

Sutton, Jonathan T; Haworth, Kevin J; Pyne-Geithman, Gail; Holland, Christy K

2014-01-01

Introduction Ultrasound (US) has been developed as both a valuable diagnostic tool and a potent promoter of beneficial tissue bioeffects for the treatment of cardiovascular disease. These effects can be mediated by mechanical oscillations of circulating microbubbles, or US contrast agents, which may also encapsulate and shield a therapeutic agent in the bloodstream. Oscillating microbubbles can create stresses directly on nearby tissue or induce fluid effects that effect drug penetration into vascular tissue, lyse thrombi or direct drugs to optimal locations for delivery. Areas covered The present review summarizes investigations that have provided evidence for US-mediated drug delivery as a potent method to deliver therapeutics to diseased tissue for cardiovascular treatment. In particular, the focus will be on investigations of specific aspects relating to US-mediated drug delivery, such as delivery vehicles, drug transport routes, biochemical mechanisms and molecular targeting strategies. Expert opinion These investigations have spurred continued research into alternative therapeutic applications, such as bioactive gas delivery and new US technologies. Successful implementation of US-mediated drug delivery has the potential to change the way many drugs are administered systemically, resulting in more effective and economical therapeutics, and less-invasive treatments. PMID:23448121

[Breech presentation and vaginal delivery: evolution of acceptability by obstetricians and patients].

PubMed

Lagrange, E; Ab der Halden, M; Ughetto, S; Boda, C; Accoceberry, M; Neyrat, C; Houlle, C; Vendittelli, F; Laurichesse-Delmas, H; Jacquetin, B; Lémery, D; Gallot, D

2007-09-01

To investigate the influence of obstetrician and patient respectively on mode of delivery in case of breech presentation at term. This retrospective study included all women with a singleton pregnancy in a breech presentation delivered at term in a tertiary care maternity unit from January 1998 to December 2004. Mode of delivery was suggested by a score based on maternal age, parity, obstetrical past history, radiopelvimetry and cephalopelvic confrontation. The obstetrician was free to follow or not the score indication and patient's informed consent was required concerning the mode of delivery. Our main outcome measurements were mode of delivery and neonatal parameters. Two hundred cases were identified. Elective cesarean section increased progressively (from 52% in 1998 to 80% in 2004 [P=0,002]). Neonatal status and proportion of score in favour of vaginal birth remained stable during the study period. The rise in cesarean section rate was mainly due to patient's request (P=0,001) whereas the trend of obstetrician in favour of cesarean did not reach significance (P=0,3). The rise of elective cesarean section for term breech delivery in a maternity unit using a predefinite score is mainly induced by patient's request. This evolution has no effect on neonatal status.

Polymeric micelles for multi-drug delivery in cancer.

PubMed

Cho, Hyunah; Lai, Tsz Chung; Tomoda, Keishiro; Kwon, Glen S

2015-02-01

Drug combinations are common in cancer treatment and are rapidly evolving, moving beyond chemotherapy combinations to combinations of signal transduction inhibitors. For the delivery of drug combinations, i.e., multi-drug delivery, major considerations are synergy, dose regimen (concurrent versus sequential), pharmacokinetics, toxicity, and safety. In this contribution, we review recent research on polymeric micelles for multi-drug delivery in cancer. In concurrent drug delivery, polymeric micelles deliver multi-poorly water-soluble anticancer agents, satisfying strict requirements in solubility, stability, and safety. In sequential drug delivery, polymeric micelles participate in pretreatment strategies that "prime" solid tumors and enhance the penetration of secondarily administered anticancer agent or nanocarrier. The improved delivery of multiple poorly water-soluble anticancer agents by polymeric micelles via concurrent or sequential regimens offers novel and interesting strategies for drug combinations in cancer treatment.

Nanocomposite thin films for triggerable drug delivery.

PubMed

Vannozzi, Lorenzo; Iacovacci, Veronica; Menciassi, Arianna; Ricotti, Leonardo

2018-05-01

Traditional drug release systems normally rely on a passive delivery of therapeutic compounds, which can be partially programmed, prior to injection or implantation, through variations in the material composition. With this strategy, the drug release kinetics cannot be remotely modified and thus adapted to changing therapeutic needs. To overcome this issue, drug delivery systems able to respond to external stimuli are highly desirable, as they allow a high level of temporal and spatial control over drug release kinetics, in an operator-dependent fashion. Areas covered: On-demand drug delivery systems actually represent a frontier in this field and are attracting an increasing interest at both research and industrial level. Stimuli-responsive thin films, enabled by nanofillers, hold a tremendous potential in the field of triggerable drug delivery systems. The inclusion of responsive elements in homogeneous or heterogeneous thin film-shaped polymeric matrices strengthens and/or adds intriguing properties to conventional (bare) materials in film shape. Expert opinion: This Expert Opinion review aims to discuss the approaches currently pursued to achieve an effective on-demand drug delivery, through nanocomposite thin films. Different triggering mechanisms allowing a fine control on drug delivery are described, together with current challenges and possible future applications in therapy and surgery.

Demonstration of vaginal colonization with GusA-expressing Lactobacillus jensenii following oral delivery in rhesus macaques

PubMed Central

Lagenaur, Laurel A; Lee, Peter P; Hamer, Dean H; Sanders-Beer, Brigitte E

2012-01-01

The vaginal microbiome, which harbors beneficial Lactobacillus strains, is believed to be a major host defense mechanism for preventing infections of the urogenital tract. It has been suggested that the gastrointestinal tract serves as a reservoir for lactobacilli that colonize the vagina. Using rhesus macaques, we examined whether oral delivery of human vaginal Lactobacillus jensenii-1153-1646, a GusA-producing strain, would result in colonization of the rectum and the vagina. Lactobacilli were identified from the vagina tracts of three macaques on the basis of β-glucuronidase enzyme production, 16S rRNA gene sequence and DNA homology using a repetitive sequence-based polymerase chain reaction. PMID:21907793

Hydrogel-Based Drug Delivery Systems for Poorly Water-Soluble Drugs.

PubMed

McKenzie, Matthew; Betts, David; Suh, Amy; Bui, Kathryn; Kim, London Doyoung; Cho, Hyunah

2015-11-13

Hydrogels are three-dimensional materials that can withstand a great amount of water incorporation while maintaining integrity. This allows hydrogels to be very unique biomedical materials, especially for drug delivery. Much effort has been made to incorporate hydrophilic molecules in hydrogels in the field of drug delivery, while loading of hydrophobic drugs has not been vastly studied. However, in recent years, research has also been conducted on incorporating hydrophobic molecules within hydrogel matrices for achieving a steady release of drugs to treat various ailments. Here, we summarize the types of hydrogels used as drug delivery vehicles, various methods to incorporate hydrophobic molecules in hydrogel matrices, and the potential therapeutic applications of hydrogels in cancer.

Recent advances of controlled drug delivery using microfluidic platforms.

PubMed

Sanjay, Sharma T; Zhou, Wan; Dou, Maowei; Tavakoli, Hamed; Ma, Lei; Xu, Feng; Li, XiuJun

2018-03-15

Conventional systematically-administered drugs distribute evenly throughout the body, get degraded and excreted rapidly while crossing many biological barriers, leaving minimum amounts of the drugs at pathological sites. Controlled drug delivery aims to deliver drugs to the target sites at desired rates and time, thus enhancing the drug efficacy, pharmacokinetics, and bioavailability while maintaining minimal side effects. Due to a number of unique advantages of the recent microfluidic lab-on-a-chip technology, microfluidic lab-on-a-chip has provided unprecedented opportunities for controlled drug delivery. Drugs can be efficiently delivered to the target sites at desired rates in a well-controlled manner by microfluidic platforms via integration, implantation, localization, automation, and precise control of various microdevice parameters. These features accordingly make reproducible, on-demand, and tunable drug delivery become feasible. On-demand self-tuning dynamic drug delivery systems have shown great potential for personalized drug delivery. This review presents an overview of recent advances in controlled drug delivery using microfluidic platforms. The review first briefly introduces microfabrication techniques of microfluidic platforms, followed by detailed descriptions of numerous microfluidic drug delivery systems that have significantly advanced the field of controlled drug delivery. Those microfluidic systems can be separated into four major categories, namely drug carrier-free micro-reservoir-based drug delivery systems, highly integrated carrier-free microfluidic lab-on-a-chip systems, drug carrier-integrated microfluidic systems, and microneedles. Microneedles can be further categorized into five different types, i.e. solid, porous, hollow, coated, and biodegradable microneedles, for controlled transdermal drug delivery. At the end, we discuss current limitations and future prospects of microfluidic platforms for controlled drug delivery. Copyright �

Vaginal health in contraceptive vaginal ring users - A review.

PubMed

Lete, Iñaki; Cuesta, María C; Marín, Juan M; Guerra, Sandra

2013-08-01

To provide an overview of the available data from clinical studies of vaginal conditions in women who use a vaginal ring as a contraceptive. A systematic review of the literature. Millions of women have already used the ethylene vinyl acetate vaginal ring that releases ethinylestradiol and etonogestrel for contraception. Because of its small size, more than four out of five women using the ring report that they do not feel it, even during sexual intercourse. No colposcopic or cytological changes have been observed in users, although approximately 10% have increased vaginal discharge. While in vitro studies have shown adhesion of Candida yeasts to the vaginal ring surface, clinical studies have not demonstrated a greater incidence of Candida infections compared to users of equivalent oral contraceptives. Some clinical studies suggest a lower incidence of bacterial vaginosis. No interaction exists between concomitant use of the vaginal ring and other drugs or products for vaginal use. The use of a contraceptive vaginal ring does not alter the vaginal ecosystem and therefore does not substantially affect vaginal health.

[Immediate fetal-maternal morbidity of first instrumental vaginal delivery using Thierry's spatulas. A prospective continuous study of 195 fetal extractions].

PubMed

Parant, O; Simon-Toulza, C; Capdet, J; Fuzier, V; Arnaud, C; Rème, J-M

2009-10-01

To investigate the immediate fetal-maternal morbidity related to Thierry's spatula for first instrumental vaginal delivery. We conducted a prospective observational study in Toulouse university hospital, including primiparas who vaginally delivered a live singleton cephalic infant>36 WG, between December 2005 and June 2006. Instrumental deliveries were performed using short spatulas in all cases. Outcome measures were: perineal complications (episiotomy, laceration and associated lesions, urinary retention, pain at H48), neonatal morbidity (cutaneous injuries, neonatal transfer, cord pH, Apgar score). Instrumental deliveries were compared with spontaneous vaginal deliveries (SVD). Six hundred and eight primiparas were included, distributed in 195 extractions (32%) and 413 SVD (68%). Spatulas allowed fetal extraction in all cases. Main differences between the two groups were: length of labour, occiput posterior position (12.8% for spatulas vs 1.7% for SVD; p<0.0001), episiotomy rate (97.9% vs 51.3%; p<0.0001), severe perineal lacerations (3.6% vs 0.2%; p=0.0007), post-partum morbidity (pain, hematoma, and urinary retention). No case of early severe neonatal complication was related to the use of the spatulas. Perineal complications (severe lacerations) associated with spatulas are increased with regard to SVD, but comparable to that reported with forceps. The main disadvantage is the high frequency of episiotomy, which should not be systematic. Neonatal morbidity is reduced. Comparative studies (spatulas vs. other procedures) are needed to confirm these data, but spatulas remain a multipurpose instrument which should continue to be taught.

Nanoparticles in the ocular drug delivery

PubMed Central

Zhou, Hong-Yan; Hao, Ji-Long; Wang, Shuang; Zheng, Yu; Zhang, Wen-Song

2013-01-01

Ocular drug transport barriers pose a challenge for drug delivery comprising the ocular surface epithelium, the tear film and internal barriers of the blood-aqueous and blood-retina barriers. Ocular drug delivery efficiency depends on the barriers and the clearance from the choroidal, conjunctival vessels and lymphatic. Traditional drug administration reduces the clinical efficacy especially for poor water soluble molecules and for the posterior segment of the eye. Nanoparticles (NPs) have been designed to overcome the barriers, increase the drug penetration at the target site and prolong the drug levels by few internals of drug administrations in lower doses without any toxicity compared to the conventional eye drops. With the aid of high specificity and multifunctionality, DNA NPs can be resulted in higher transfection efficiency for gene therapy. NPs could target at cornea, retina and choroid by surficial applications and intravitreal injection. This review is concerned with recent findings and applications of NPs drug delivery systems for the treatment of different eye diseases. PMID:23826539

Colloidal microgels in drug delivery applications

PubMed Central

Vinogradov, Serguei V.

2005-01-01

Colloidal microgels have recently received attention as environmentally responsive systems and now are increasingly used in applications as carriers for therapeutic drugs and diagnostic agents. Synthetic microgels consist of a crosslinked polymer network that provides a depot for loaded drugs, protection against environmental hazards and template for post-synthetic modification or vectorization of the drug carriers. The aim of this manuscript is to review recent attempts to develop new microgel formulations for oral drug delivery, to design metal-containing microgels for diagnostic and therapeutic applications, and to advance approaches including the systemic administration of microgels. Novel nanogel drug delivery systems developed in the authors’ laboratory are discussed in details including aspects of their synthesis, vectorization and recent applications for encapsulation of low molecular weight drugs or formulation of biological macromolecules. The findings reviewed here are encouraging for further development of the nanogels as intelligent drug carriers with such features as targeted delivery and triggered drug release. PMID:17168773

Synthetic Tumor Networks for Screening Drug Delivery Systems

PubMed Central

Prabhakarpandian, Balabhaskar; Shen, Ming-Che; Nichols, Joseph B.; Garson, Charles J.; Mills, Ivy R.; Matar, Majed M.; Fewell, Jason G.; Pant, Kapil

2015-01-01

Tumor drug delivery is a complex phenomenon affected by several elements in addition to drug or delivery vehicle’s physico-chemical properties. A key factor is tumor microvasculature with complex effects including convective transport, high interstitial pressure and enhanced vascular permeability due to the presence of “leaky vessels”. Current in vitro models of the tumor microenvironment for evaluating drug delivery are oversimplified and, as a result, show poor correlation with in vivo performance. In this study, we report on the development of a novel microfluidic platform that models the tumor microenvironment more accurately, with physiologically and morphologically realistic microvasculature including endothelial cell lined leaky capillary vessels along with 3D solid tumors. Endothelial cells and 3D spheroids of cervical tumor cells were co-cultured in the networks. Drug vehicle screening was demonstrated using GFP gene delivery by different formulations of nanopolymers. The synthetic tumor network was successful in predicting in vivo delivery efficiencies of the drug vehicles. The developed assay will have critical applications both in basic research, where it can be used to develop next generation delivery vehicles, and in drug discovery where it can be used to study drug transport and delivery efficacy in realistic tumor microenvironment, thereby enabling drug compound and/or delivery vehicle screening. PMID:25599856

Non-invasive systemic drug delivery through mucosal routes.

PubMed

Goyal, Amit K; Singh, Ranjit; Chauhan, Gaurav; Rath, Goutam

2018-04-24

Science of drug delivery has achieved tremendous milestones in the last few decades. Emergence of novel drug delivery techniques and the most popular nanotechnology directed the drug delivery to another level. Without any doubt, present technology holds the proficiency to approach even the intercellular targets. Between all these success auras, there lies wads of giant challenges. One such challenge is delivering the molecule directly to the blood stream. Parenteral route is considered as the most effective route for delivering active pharmaceutical substances, but is associated with major disadvantages of painful drug delivery. Modern drug delivery suggests several approaches to outstrip this painful phenomenon. In the present article, we represent a new systematic vision to understand the ability and desirability of mucosal sites to achieve painless drug delivery. Human mucosa presents supreme proximity to the blood circulation that one can even observe with naked eye. Advances in drug delivery provide numerous approaches to exploit the mucosa for systemic reach. However, the revolutionary success is still unapproachable, with an understandable reason of associated complexities and challenges. This manuscript summarizes the significance of each mucosal site, on the basis of anatomical-physiological grounds. Particular attention is given to rationalize the selection of disease and a suitable drug delivery approach for its treatment.

The Research Progress of Targeted Drug Delivery Systems

NASA Astrophysics Data System (ADS)

Zhan, Jiayin; Ting, Xizi Liang; Zhu, Junjie

2017-06-01

Targeted drug delivery system (DDS) means to selectively transport drugs to targeted tissues, organs, and cells through a variety of drugs carrier. It is usually designed to improve the pharmacological and therapeutic properties of conventional drugs and to overcome problems such as limited solubility, drug aggregation, poor bio distribution and lack of selectivity, controlling drug release carrier and to reduce normal tissue damage. With the characteristics of nontoxic and biodegradable, it can increase the retention of drug in lesion site and the permeability, improve the concentration of the drug in lesion site. at present, there are some kinds of DDS using at test phase, such as slow controlled release drug delivery system, targeted drug delivery systems, transdermal drug delivery system, adhesion dosing system and so on. This paper makes a review for DDS.

Novel drug delivery systems for glaucoma

PubMed Central

Lavik, E; Kuehn, M H; Kwon, Y H

2011-01-01

Reduction of intraocular pressure (IOP) by pharmaceutical or surgical means has long been the standard treatment for glaucoma. A number of excellent drugs are available that are effective in reducing IOP. These drugs are typically applied as eye drops. However, patient adherence can be poor, thus reducing the clinical efficacy of the drugs. Several novel delivery systems designed to address the issue of adherence and to ensure consistent reduction of IOP are currently under development. These delivery systems include contact lenses-releasing glaucoma medications, injectables such as biodegradable micro- and nanoparticles, and surgically implanted systems. These new technologies are aimed at increasing clinical efficacy by offering multiple delivery options and are capable of managing IOP for several months. There is also a desire to have complementary neuroprotective approaches for those who continue to show progression, despite IOP reduction. Many potential neuroprotective agents are not suitable for traditional oral or drop formulations. Their potential is dependent on developing suitable delivery systems that can provide the drugs in a sustained, local manner to the retina and optic nerve. Drug delivery systems have the potential to improve patient adherence, reduce side effects, increase efficacy, and ultimately, preserve sight for glaucoma patients. In this review, we discuss benefits and limitations of the current systems of delivery and application, as well as those on the horizon. PMID:21475311

Intracarotid Delivery of Drugs: The Potential and the Pitfalls

PubMed Central

Joshi, Shailendra; Meyers, Phillip M.; Ornstein, Eugene

2014-01-01

The major efforts to selectively deliver drugs to the brain in the last decade have relied on smart molecular techniques to penetrate the blood brain barrier while intraarterial drug delivery has drawn relatively little attention. In the last decade there have been rapid advances in endovascular techniques. Modern endovascular procedures can permit highly targeted drug delivery by intracarotid route. Intracarotid drug delivery can be the primary route of drug delivery or it could be used to facilitate the delivery of smart-neuropharmaceuticals. There have been few attempts to systematically understand the kinetics of intracarotid drugs. Anecdotal data suggests that intracarotid drug delivery is effective in the treatment of cerebral vasospasm, thromboembolic strokes, and neoplasms. Neuroanesthesiologists are frequently involved in the care of such high-risk patients. Therefore, it is necessary to understand the applications of intracarotid drug delivery and the unusual kinetics of intracarotid drugs. PMID:18719453

Nanocrystal for ocular drug delivery: hope or hype.

PubMed

Sharma, Om Prakash; Patel, Viral; Mehta, Tejal

2016-08-01

The complexity of the structure and nature of the eye emanates a challenge for drug delivery to formulation scientists. Lower bioavailability concern of conventional ocular formulation provokes the interest of researchers in the development of novel drug delivery system. Nanotechnology-based formulations have been extensively investigated and found propitious in improving bioavailability of drugs by overcoming ocular barriers prevailing in the eye. The advent of nanocrystals helped in combating the problem of poorly soluble drugs specifically for oral and parenteral drug delivery and led to development of various marketed products. Nanocrystal-based formulations explored for ocular drug delivery have been found successful in achieving increase in retention time, bioavailability, and permeability of drugs across the corneal and conjunctival epithelium. In this review, we have highlighted the ocular physiology and barriers in drug delivery. A comparative analysis of various nanotechnology-based ocular formulations is done with their pros and cons. Consideration is also given to various methods of preparation of nanocrystals with their patented technology. This article highlights the success achieved in conquering various challenges of ocular delivery by the use of nanocrystals while emphasizing on its advantages and application for ocular formulation. The perspectives of nanocrystals as an emerging flipside to explore the frontiers of ocular drug delivery are discussed.

[Impact of the external cephalic version on the obstetrical prognosis in a team with a high success rate of vaginal delivery in breech presentation].

PubMed

Coppola, C; Mottet, N; Mariet, A S; Baeza, C; Poitrey, E; Bourtembourg, A; Ramanah, R; Riethmuller, D

2016-10-01

To analyse the impact of external cephalic version (ECV) on caesarean section rate in a team with a high success rate of vaginal delivery in breech presentation. Retrospective monocentric study including 298 patients with a breech presentations between 33 and 35weeks of amenorrhea followed at our university hospital and delivered after 35weeks, between 1st January 2011 and 31st December 2013. Patients were divided into 2 groups: planned ECV (n=216 patients) versus no planned ECV (n=57 patients). Our rate of successful vaginal breech delivery over the period of the study was 61.1%. We performed 165 ECV, with a 21.8% success rate. The average term of the attempt of ECV was 36.7weeks of amenorrhea. The caesarean section rate was not significantly different in the planned ECV group, even after adjustment on age, parity and previous caesarean delivery (adjusted OR=1.67 [0.77-3.61]). Attempt of ECV did not reduce the number of breech presentation at delivery (61.1% versus 61.4% [P=0.55]). Planned ECV in our center with a high level of breech vaginal delivery did not significantly impact our cesarean section rate. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Microencapsulation: A promising technique for controlled drug delivery.

PubMed

Singh, M N; Hemant, K S Y; Ram, M; Shivakumar, H G

2010-07-01

MICROPARTICLES OFFER VARIOUS SIGNIFICANT ADVANTAGES AS DRUG DELIVERY SYSTEMS, INCLUDING: (i) an effective protection of the encapsulated active agent against (e.g. enzymatic) degradation, (ii) the possibility to accurately control the release rate of the incorporated drug over periods of hours to months, (iii) an easy administration (compared to alternative parenteral controlled release dosage forms, such as macro-sized implants), and (iv) Desired, pre-programmed drug release profiles can be provided which match the therapeutic needs of the patient. This article gives an overview on the general aspects and recent advances in drug-loaded microparticles to improve the efficiency of various medical treatments. An appropriately designed controlled release drug delivery system can be a foot ahead towards solving problems concerning to the targeting of drug to a specific organ or tissue, and controlling the rate of drug delivery to the target site. The development of oral controlled release systems has been a challenge to formulation scientist due to their inability to restrain and localize the system at targeted areas of gastrointestinal tract. Microparticulate drug delivery systems are an interesting and promising option when developing an oral controlled release system. The objective of this paper is to take a closer look at microparticles as drug delivery devices for increasing efficiency of drug delivery, improving the release profile and drug targeting. In order to appreciate the application possibilities of microcapsules in drug delivery, some fundamental aspects are briefly reviewed.

Microencapsulation: A promising technique for controlled drug delivery

PubMed Central

Singh, M.N.; Hemant, K.S.Y.; Ram, M.; Shivakumar, H.G.

2010-01-01

Microparticles offer various significant advantages as drug delivery systems, including: (i) an effective protection of the encapsulated active agent against (e.g. enzymatic) degradation, (ii) the possibility to accurately control the release rate of the incorporated drug over periods of hours to months, (iii) an easy administration (compared to alternative parenteral controlled release dosage forms, such as macro-sized implants), and (iv) Desired, pre-programmed drug release profiles can be provided which match the therapeutic needs of the patient. This article gives an overview on the general aspects and recent advances in drug-loaded microparticles to improve the efficiency of various medical treatments. An appropriately designed controlled release drug delivery system can be a foot ahead towards solving problems concerning to the targeting of drug to a specific organ or tissue, and controlling the rate of drug delivery to the target site. The development of oral controlled release systems has been a challenge to formulation scientist due to their inability to restrain and localize the system at targeted areas of gastrointestinal tract. Microparticulate drug delivery systems are an interesting and promising option when developing an oral controlled release system. The objective of this paper is to take a closer look at microparticles as drug delivery devices for increasing efficiency of drug delivery, improving the release profile and drug targeting. In order to appreciate the application possibilities of microcapsules in drug delivery, some fundamental aspects are briefly reviewed. PMID:21589795

Advanced Analgesic Drug Delivery and Nanobiotechnology.

PubMed

Stoicea, Nicoleta; Fiorda-Diaz, Juan; Joseph, Nicholas; Shabsigh, Muhammad; Arias-Morales, Carlos; Gonzalez-Zacarias, Alicia A; Mavarez-Martinez, Ana; Marjoribanks, Stephen; Bergese, Sergio D

2017-07-01

Transdermal administration of analgesic medications offers several benefits over alternative routes of administration, including a decreased systemic drug load with fewer side effects, and avoidance of drug degradation by the gastrointestinal tract. Transdermal administration also offers a convenient mode of drug administration over an extended period of time, particularly desirable in pain medicine. A transdermal administration route may also offer increased safety for drugs with a narrow therapeutic window. The primary barrier to transdermal drug absorption is the skin itself. Transdermal nanotechnology offers a novel method of achieving enhanced dermal penetration with an extended delivery profile for analgesic drugs, due to their small size and relatively large surface area. Several materials have been used to enhance drug duration and transdermal penetration. The application of nanotechnology in transdermal delivery of analgesics has raised new questions regarding safety and ethical issues. The small molecular size of nanoparticles enables drug delivery to previously inaccessible body sites. To ensure safety, the interaction of nanoparticles with the human body requires further investigation on an individual drug basis, since different formulations have unique properties and side effects.

Reservoir-Based Drug Delivery Systems Utilizing Microtechnology

PubMed Central

Stevenson, Cynthia L.; Santini, John T.; Langer, Robert

2012-01-01

This review covers reservoir-based drug delivery systems that incorporate microtechnology, with an emphasis on oral, dermal, and implantable systems. Key features of each technology are highlighted such as working principles, fabrication methods, dimensional constraints, and performance criteria. Reservoir-based systems include a subset of microfabricated drug delivery systems and provide unique advantages. Reservoirs, whether external to the body or implanted, provide a well-controlled environment for a drug formulation, allowing increased drug stability and prolonged delivery times. Reservoir systems have the flexibility to accommodate various delivery schemes, including zero order, pulsatile, and on demand dosing, as opposed to a standard sustained release profile. Furthermore, the development of reservoir-based systems for targeted delivery for difficult to treat applications (e.g., ocular) has resulted in potential platforms for patient therapy. PMID:22465783

Physiologically-based pharmacokinetic model of vaginally administered dapivirine ring and film formulations.

PubMed

Kay, Katherine; Shah, Dhaval K; Rohan, Lisa; Bies, Robert

2018-05-01

A physiologically-based pharmacokinetic (PBPK) model of the vaginal space was developed with the aim of predicting concentrations in the vaginal and cervical space. These predictions can be used to optimize the probability of success of vaginally administered dapivirine (DPV) for HIV prevention. We focus on vaginal delivery using either a ring or film. A PBPK model describing the physiological structure of the vaginal tissue and fluid was defined mathematically and implemented in MATLAB. Literature reviews provided estimates for relevant physiological and physiochemical parameters. Drug concentration-time profiles were simulated in luminal fluids, vaginal tissue and plasma after administration of ring or film. Patient data were extracted from published clinical trials and used to test model predictions. The DPV ring simulations tested the two dosing regimens and predicted PK profiles and area under the curve of luminal fluids (29 079 and 33 067 mg h l -1 in groups A and B, respectively) and plasma (0.177 and 0.211 mg h l -1 ) closely matched those reported (within one standard deviation). While the DPV film study reported drug concentration at only one time point per patient, our simulated profiles pass through reported concentration range. HIV is a major public health issue and vaginal microbicides have the potential to provide a crucial, female-controlled option for protection. The PBPK model successfully simulated realistic representations of drug PK. It provides a reliable, inexpensive and accessible platform where potential effectiveness of new compounds and the robustness of treatment modalities for pre-exposure prophylaxis can be evaluated. © 2018 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Drug delivery with microsecond laser pulses into gelatin

NASA Astrophysics Data System (ADS)

Shangguan, Hanqun; Casperson, Lee W.; Shearin, Alan; Gregory, Kenton W.; Prahl, Scott A.

1996-07-01

Photoacoustic drug delivery is a technique for localized drug delivery by laser-induced hydrodynamic pressure following cavitation bubble expansion and collapse. Photoacoustic drug delivery was investigated on gelatin-based thrombus models with planar and cylindrical geometries by use of one microsecond laser pulses. Solutions of a hydrophobic dye in mineral oil permitted monitoring of delivered colored oil into clear gelatin-based thrombus models. Cavitation bubble development and photoacoustic drug delivery were visualized with flash photography. This study demonstrated that cavitation is the governing mechanism for photoacoustic drug delivery, and the deepest penetration of colored oil in gels followed the bubble collapse. Spatial distribution measurements revealed that colored oil could be driven a few millimeters into the gels in both axial and radial directions, and the penetration was less than 500 mu m when the gelatin structure was not fractured. localized drug delivery, cavitation bubble, laser thrombolysis.

Advanced Drug Delivery Systems for Transdermal Delivery of Non-Steroidal Anti-Inflammatory Drugs: A Review.

PubMed

Kumar, Lalit; Verma, Shivani; Singh, Mehakjot; Tamanna, Tamanna; Utreja, Puneet

2018-06-04

Transdermal route of delivery of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) has several advantages over other routes like reduced adverse effects, less systemic absorption, and avoidance of first pass effect and degradation in the gastrointestinal tract (GIT). Transdermal route is also beneficial for drugs having a narrow therapeutic index. The skin acts as the primary barrier for transdermal delivery of various therapeutic molecules. Various advanced nanocarrier systems offer several advantages like improved dermal penetration along with an extended drug release profile due to their smaller size and high surface area. Various nanocarrier explored for transdermal delivery of NSAIDs are liposomes, niosomes, ethosomes, polymeric nanoparticles (NPs), solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), dendrimers, nanosuspensions/nanoemulsion, and nanofibers Objectives: In the present review, our major aim was to explore the therapeutic potential of advanced nanocarrier systems enlisted above for transdermal delivery of NSAIDs. All literature search regarding advanced nanocarrier systems for transdermal delivery of NSAIDs was done using Google Scholar and Pubmed. Advanced nanocarrier have shown various advantages like reduced side effect, low dosing frequency, high skin permeation, and ease of application over conventional transdermal delivery systems of NSAIDs in various preclinical studies. However, clinical exploration of advanced nanocarrier systems for transdermal delivery of NSAIDs is still a challenge. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Biopolymers as transdermal drug delivery systems in dermatology therapy.

PubMed

Basavaraj, K H; Johnsy, George; Navya, M A; Rashmi, R; Siddaramaiah

2010-01-01

The skin is considered a complex organ for drug delivery because of its structure. Drug delivery systems are designed for the controlled release of drugs through the skin into the systemic circulation, maintaining consistent efficacy and reducing the dose of the drugs and their related side effects. Transdermal drug delivery represents one of the most rapidly advancing areas of novel drug delivery. The excellent impervious nature of the skin is the greatest challenge that must be overcome for successful drug delivery. Today, polymers have been proven to be successful for long-term drug delivery applications as no single polymer can satisfy all of the requirements. Biopolymers in the field of dermal application are rare and the mechanisms that affect skin absorption are almost unknown. Biopolymers are widely used as drug delivery systems, but as such the use of biopolymers as drug delivery systems in dermatologic therapy is still in progress. Commonly used biopolymers include hydrocolloids, alginates, hydrogels, polyurethane, collagen, poly(lactic-co-glycolic acid), chitosan, proteins and peptides, pectin, siRNAs, and hyaluronic acid. These new and exciting methods for drug delivery are already increasing the number and quality of dermal and transdermal therapies. This article reviews current research on biopolymers and focuses on their potential as drug carriers, particularly in relation to the dermatologic aspects of their use.

Spray-on transdermal drug delivery systems.

PubMed

Ibrahim, Sarah A

2015-02-01

Transdermal drug delivery possesses superior advantages over other routes of administration, particularly minimizing first-pass metabolism. Transdermal drug delivery is challenged by the barrier nature of skin. Numerous technologies have been developed to overcome the relatively low skin permeability, including spray-on transdermal systems. A transdermal spray-on system (TSS) usually consists of a solution containing the drug, a volatile solvent and in many cases a chemical penetration enhancer. TSS promotes drug delivery via the complex interplay between solvent evaporation and drug-solvent drag into skin. The volatile solvent carries the drug into the upper layers of the stratum corneum, and as the volatile solvent evaporates, an increase in the thermodynamic activity of the drug occurs resulting in an increased drug loading in skin. TSS is easily applied, delivering flexible drug dosage and associated with lower incidence of skin irritation. TSS provides a fast-drying product where the volatile solvent enables uniform drug distribution with minimal vehicle deposition on skin. TSS ensures precise dose administration that is aesthetically appealing and eliminates concerns of residual drug associated with transdermal patches. Furthermore, it provides a better alternative to traditional transdermal products due to ease of product development and manufacturing.

Light-switchable systems for remotely controlled drug delivery.

PubMed

Shim, Gayong; Ko, Seungbeom; Kim, Dongyoon; Le, Quoc-Viet; Park, Gyu Thae; Lee, Jaiwoo; Kwon, Taekhyun; Choi, Han-Gon; Kim, Young Bong; Oh, Yu-Kyoung

2017-12-10

Light-switchable systems have recently received attention as a new mode of remotely controlled drug delivery. In the past, a multitude of nanomedicine studies have sought to enhance the specificity of drug delivery to target sites by focusing on receptors overexpressed on malignant cells or environmental features of diseases sites. Despite these immense efforts, however, there are few clinically available nanomedicines. We need a paradigm shift in drug delivery. One strategy that may overcome the limitations of pathophysiology-based drug delivery is the use of remotely controlled delivery technology. Unlike pathophysiology-based active drug targeting strategies, light-switchable systems are not affected by the heterogeneity of cells, tissue types, and/or microenvironments. Instead, they are triggered by remote light (i.e., near-infrared) stimuli, which are absorbed by photoresponsive molecules or three-dimensional nanostructures. The sequential conversion of light to heat or reactive oxygen species can activate drug release and allow it to be spatio-temporally controlled. Light-switchable systems have been used to activate endosomal drug escape, modulate the release of chemical and biological drugs, and alter nanoparticle structures to control the release rates of drugs. This review will address the limitations of pathophysiology-based drug delivery systems, the current status of light-based remote-switch systems, and future directions in the application of light-switchable systems for remotely controlled drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

Recent advances in chitosan-based nanoparticulate pulmonary drug delivery

NASA Astrophysics Data System (ADS)

Islam, Nazrul; Ferro, Vito

2016-07-01

The advent of biodegradable polymer-encapsulated drug nanoparticles has made the pulmonary route of administration an exciting area of drug delivery research. Chitosan, a natural biodegradable and biocompatible polysaccharide has received enormous attention as a carrier for drug delivery. Recently, nanoparticles of chitosan (CS) and its synthetic derivatives have been investigated for the encapsulation and delivery of many drugs with improved targeting and controlled release. Herein, recent advances in the preparation and use of micro-/nanoparticles of chitosan and its derivatives for pulmonary delivery of various therapeutic agents (drugs, genes, vaccines) are reviewed. Although chitosan has wide applications in terms of formulations and routes of drug delivery, this review is focused on pulmonary delivery of drug-encapsulated nanoparticles of chitosan and its derivatives. In addition, the controversial toxicological effects of chitosan nanoparticles for lung delivery will also be discussed.

Genetically engineered nanocarriers for drug delivery.

PubMed

Shi, Pu; Gustafson, Joshua A; MacKay, J Andrew

2014-01-01

Cytotoxicity, low water solubility, rapid clearance from circulation, and off-target side-effects are common drawbacks of conventional small-molecule drugs. To overcome these shortcomings, many multifunctional nanocarriers have been proposed to enhance drug delivery. In concept, multifunctional nanoparticles might carry multiple agents, control release rate, biodegrade, and utilize target-mediated drug delivery; however, the design of these particles presents many challenges at the stage of pharmaceutical development. An emerging solution to improve control over these particles is to turn to genetic engineering. Genetically engineered nanocarriers are precisely controlled in size and structure and can provide specific control over sites for chemical attachment of drugs. Genetically engineered drug carriers that assemble nanostructures including nanoparticles and nanofibers can be polymeric or non-polymeric. This review summarizes the recent development of applications in drug and gene delivery utilizing nanostructures of polymeric genetically engineered drug carriers such as elastin-like polypeptides, silk-like polypeptides, and silk-elastin-like protein polymers, and non-polymeric genetically engineered drug carriers such as vault proteins and viral proteins.

Genetically engineered nanocarriers for drug delivery

PubMed Central

Shi, Pu; Gustafson, Joshua A; MacKay, J Andrew

2014-01-01

Cytotoxicity, low water solubility, rapid clearance from circulation, and off-target side-effects are common drawbacks of conventional small-molecule drugs. To overcome these shortcomings, many multifunctional nanocarriers have been proposed to enhance drug delivery. In concept, multifunctional nanoparticles might carry multiple agents, control release rate, biodegrade, and utilize target-mediated drug delivery; however, the design of these particles presents many challenges at the stage of pharmaceutical development. An emerging solution to improve control over these particles is to turn to genetic engineering. Genetically engineered nanocarriers are precisely controlled in size and structure and can provide specific control over sites for chemical attachment of drugs. Genetically engineered drug carriers that assemble nanostructures including nanoparticles and nanofibers can be polymeric or non-polymeric. This review summarizes the recent development of applications in drug and gene delivery utilizing nanostructures of polymeric genetically engineered drug carriers such as elastin-like polypeptides, silk-like polypeptides, and silk-elastin-like protein polymers, and non-polymeric genetically engineered drug carriers such as vault proteins and viral proteins. PMID:24741309

Drug delivery technologies for autoimmune disease.

PubMed

Phillips, Brett E; Giannoukakis, Nick

2010-11-01

Targeting autoimmune disease poses two main challenges. The first is to identify unique targets to suppress directly or indirectly autoreactive cells exclusively. The second is to penetrate target tissues to deliver specifically drugs to desired cells that can achieve a therapeutic outcome. Herein, the range of drug delivery methods available and under development and how they can be useful to treat autoimmune diseases are discussed. Polymer delivery methods, as well as biological methods that include fusion proteins, targeted antibodies, recombinant viruses and cell products are compared. Readers will gain insight into the progression of clinical trials for different technologies and drug delivery methods useful for targeting and modulating the function of autoreactive immune cells. Several tissue-specific polymer-based and biologic drug delivery systems are now in Phase II/III clinical trials. Although these trials are focused mainly on cancer treatment, lessons from these trials can guide the use of the same agents for autoimmunity therapeutics.

The impact of occiput posterior fetal head position on the risk of anal sphincter injury in forceps-assisted vaginal deliveries.

PubMed

Benavides, Lorena; Wu, Jennifer M; Hundley, Andrew F; Ivester, Thomas S; Visco, Anthony G

2005-05-01

A forceps-assisted vaginal delivery is a well-recognized risk factor for anal sphincter injury. Some studies have shown that occiput posterior (OP) fetal head position is also associated with an increased risk for third- or fourth-degree lacerations. The objective of this study was to assess whether OP position confers an incrementally increased risk for anal sphincter injury above that present with forceps deliveries. This was a retrospective cohort study of 588 singleton, cephalic, forceps-assisted vaginal deliveries performed at our institution between January 1996 and October 2003. Maternal demographics, labor and delivery characteristics, and neonatal factors were examined. Statistical analysis consisted of univariate statistics, Student t test, chi2, and logistic regression. The prevalence of occiput anterior (OA) and OP positions was 88.4% and 11.6%, respectively. The groups were similar in age, marital status, body mass index, use of epidural, frequency of inductions, episiotomies, and shoulder dystocias. The OA group had a higher frequency of rotational forceps (16.2% vs 5.9%, P = .03), greater birth weights (3304 +/- 526 g vs 3092 +/- 777 g, P = .004), and a larger percentage of white women (48.8% vs 34.3%, P = .04). Overall, 35% of forceps deliveries resulted in a third- or fourth-degree laceration. Anal sphincter injury occurred significantly more often in the OP group compared with the OA group (51.5% vs 32.9%, P = .003), giving an odds ratio of 2.2 (CI: 1.3-3.6). In a logistic regression model that controlled for occiput posterior position, maternal body mass index, race, length of second stage, episiotomy, birth weight, and rotational forceps, OP head position was 3.1 (CI: 1.6-6.2) times more likely to be associated with anal sphincter injury than OA head position. Forceps-assisted vaginal deliveries have been associated with a greater risk for anal sphincter injury. Within this population of forceps deliveries, an OP position further increases the

Controlled drug delivery systems: past forward and future back.

PubMed

Park, Kinam

2014-09-28

Controlled drug delivery technology has progressed over the last six decades. This progression began in 1952 with the introduction of the first sustained release formulation. The 1st generation of drug delivery (1950-1980) focused on developing oral and transdermal sustained release systems and establishing controlled drug release mechanisms. The 2nd generation (1980-2010) was dedicated to the development of zero-order release systems, self-regulated drug delivery systems, long-term depot formulations, and nanotechnology-based delivery systems. The latter part of the 2nd generation was largely focused on studying nanoparticle formulations. The Journal of Controlled Release (JCR) has played a pivotal role in the 2nd generation of drug delivery technologies, and it will continue playing a leading role in the next generation. The best path towards a productive 3rd generation of drug delivery technology requires an honest, open dialog without any preconceived ideas of the past. The drug delivery field needs to take a bold approach to designing future drug delivery formulations primarily based on today's necessities, to produce the necessary innovations. The JCR provides a forum for sharing the new ideas that will shape the 3rd generation of drug delivery technology. Copyright © 2014 Elsevier B.V. All rights reserved.

Introduction for Design of Nanoparticle Based Drug Delivery Systems.

PubMed

Edgar, Jun Yan Chan; Wang, Hui

2017-01-01

Conventional drug delivery systems contain numerous limitations such as limited targeting, low therapeutic indices, poor water solubility, and the induction of drug resistances. In order to overcome the drawbacks of conventional pathway of drug delivery, nanoparticle delivery systems are therefore designed and used as the drug carriers. Nanoparticle based drug delivery systems have been rapidly growing and are being applied to various sections of biomedicine. Drug nanocarriers based on dendrimers, liposomes, self-assembling peptides, watersoluble polymers, and block copolymer micelles are the most extensively studied types of drug delivery systems and some of them are being used in clinical therapy. In particular for cancer therapy, antineoplastic drugs are taking advantage of nanoparticulate drug carriers to improve the cure efficacy. Nanoparticle based drug carriers are capable of improving the therapeutic effectiveness of the drugs by using active targeting for the site-specific delivery, passive targeting mechanisms such as enhanced permeability and retention (EPR), de novo synthesis and uptake of low density liposome in cancer cells or by being water-soluble to improve the suboptimal pharmacokinetics in limited water-soluble delivery methods. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Enzyme-Responsive Nanomaterials for Controlled Drug Delivery

PubMed Central

Hu, Quanyin; Katti, Prateek S.; Gu, Zhen

2015-01-01

Enzymes underpin physiological function and exhibit dysregulation in many disease-associated microenvironments and aberrant cell processes. Exploiting altered enzyme activity and expression for diagnostics, drug targeting, and drug release is tremendously promising. When combined with booming research in nanobiotechnology, enzyme-responsive nanomaterials for controlled drug release have achieved significant development and been studied as an important class of drug delivery devices in nanomedicine. In this review, we describe enzymes such as proteases, phospholipase and oxidoreductases that serve as delivery triggers. Subsequently, we explore recently developed enzyme-responsive nanomaterials with versatile applications for extracellular and intracellular drug delivery. We conclude by discussing future opportunities and challenges in this area. PMID:25251024

Enzyme-responsive nanomaterials for controlled drug delivery

NASA Astrophysics Data System (ADS)

Hu, Quanyin; Katti, Prateek S.; Gu, Zhen

2014-10-01

Enzymes underpin physiological function and exhibit dysregulation in many disease-associated microenvironments and aberrant cell processes. Exploiting altered enzyme activity and expression for diagnostics, drug targeting, and drug release is tremendously promising. When combined with booming research in nanobiotechnology, enzyme-responsive nanomaterials used for controlled drug release have achieved significant development and have been studied as an important class of drug delivery strategies in nanomedicine. In this review, we describe enzymes such as proteases, phospholipases and oxidoreductases that serve as delivery triggers. Subsequently, we explore recently developed enzyme-responsive nanomaterials with versatile applications for extracellular and intracellular drug delivery. We conclude by discussing future opportunities and challenges in this area.

Chitosan Microspheres in Novel Drug Delivery Systems

PubMed Central

Mitra, Analava; Dey, Baishakhi

2011-01-01

The main aim in the drug therapy of any disease is to attain the desired therapeutic concentration of the drug in plasma or at the site of action and maintain it for the entire duration of treatment. A drug on being used in conventional dosage forms leads to unavoidable fluctuations in the drug concentration leading to under medication or overmedication and increased frequency of dose administration as well as poor patient compliance. To minimize drug degradation and loss, to prevent harmful side effects and to increase drug bioavailability various drug delivery and drug targeting systems are currently under development. Handling the treatment of severe disease conditions has necessitated the development of innovative ideas to modify drug delivery techniques. Drug targeting means delivery of the drug-loaded system to the site of interest. Drug carrier systems include polymers, micelles, microcapsules, liposomes and lipoproteins to name some. Different polymer carriers exert different effects on drug delivery. Synthetic polymers are usually non-biocompatible, non-biodegradable and expensive. Natural polymers such as chitin and chitosan are devoid of such problems. Chitosan comes from the deacetylation of chitin, a natural biopolymer originating from crustacean shells. Chitosan is a biocompatible, biodegradable, and nontoxic natural polymer with excellent film-forming ability. Being of cationic character, chitosan is able to react with polyanions giving rise to polyelectrolyte complexes. Hence chitosan has become a promising natural polymer for the preparation of microspheres/nanospheres and microcapsules. The techniques employed to microencapsulate with chitosan include ionotropic gelation, spray drying, emulsion phase separation, simple and complex coacervation. This review focuses on the preparation, characterization of chitosan microspheres and their role in novel drug delivery systems. PMID:22707817

Nanocarriers in ocular drug delivery: an update review.

PubMed

Wadhwa, Sheetu; Paliwal, Rishi; Paliwal, Shivani Rai; Vyas, S P

2009-01-01

Controlled drug delivery to eye is one of the most challenging fields of pharmaceutical research. Low drug-contact time and poor ocular bioavailability due to drainage of solution, tear turnover and its dilution or lacrimation are the problems associated with conventional systems. In addition, anatomical barriers and physiological conditions of eye are also important parameters which control designing of drug delivery systems. Nanosized carriers like micro/nano-suspensions, liposome, niosome, dendrimer, nanoparticles, ocular inserts, implants, hydrogels and prodrug approaches have been developed for this purpose. These novel systems offer manifold advantages over conventional systems as they increase the efficiency of drug delivery by improving the release profile and also reduce drug toxicity. Conventional delivery systems get diluted with tear, washed away through the lacrimal gland and usually require administering at regular time intervals whereas nanocarriers release drug at constant rate for a prolonged period of time and thus enhance its absorption and site specific delivery. This review presents an overview of the various aspects of the ocular drug delivery, with special emphasis on nanocarrier based strategies, including structure of eye, its barriers, delivery routes and the challenges/limitations associated with development of novel nanocarriers. The recent progresses in therapy of ocular disease like gene therapy have also been included so that future options should also be considered from the delivery point of view. Recent progress in the delivery of proteins and peptides via ocular route has also been incorporated for reader benefit.

Controlled-release biodegradable nanoparticles: From preparation to vaginal applications.

PubMed

Martínez-Pérez, Beatriz; Quintanar-Guerrero, David; Tapia-Tapia, Melina; Cisneros-Tamayo, Ricardo; Zambrano-Zaragoza, María L; Alcalá-Alcalá, Sergio; Mendoza-Muñoz, Néstor; Piñón-Segundo, Elizabeth

2018-03-30

This study aimed to prepare poly (d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) with chitosan (CTS) surface modification to be used as a vaginal delivery system for antimycotic drugs. Clotrimazole was encapsulated with entrapment efficiencies of 86.1 and 68.9% into Clotrimazole-PLGA-NPs (CLT-PLGA-NPs) and PLGA-NPs with CTS-modified surface (CLT-PLGA-CTS-NPs), respectively. The later NPs exhibited a larger size and higher positive zeta potential (Z potential) in comparison to unmodified NPs. In vitro release kinetic studies indicated that Clotrimazole was released in percentages of >98% from both nanoparticulate systems after 18days. Antifungal activity and mucoadhesive properties of NPs were enhanced when CTS was added onto the surface. In summary, these results suggested that Clotrimazole loaded into PLGA-CTS-NPs has great potential for vaginal applications in treating vaginal infections generated by Candida albicans. Copyright © 2018 Elsevier B.V. All rights reserved.

Nanoparticle-Hydrogel: A Hybrid Biomaterial System for Localized Drug Delivery

PubMed Central

Gao, Weiwei; Zhang, Yue; Zhang, Qiangzhe; Zhang, Liangfang

2016-01-01

Nanoparticles have offered a unique set of properties for drug delivery including high drug loading capacity, combinatorial delivery, controlled and sustained drug release, prolonged stability and lifetime, and targeted delivery. To further enhance therapeutic index, especially for localized application, nanoparticles have been increasingly combined with hydrogels to form a hybrid biomaterial system for controlled drug delivery. Herein, we review recent progresses in engineering such nanoparticle-hydrogel hybrid system (namely ‘NP-gel’) with a particular focus on its application for localized drug delivery. Specifically, we highlight four research areas where NP-gel has shown great promises, including (1) passively controlled drug release, (2) stimuli-responsive drug delivery, (3) site-specific drug delivery, and (4) detoxification. Overall, integrating therapeutic nanoparticles with hydrogel technologies creates a unique and robust hybrid biomaterial system that enables effective localized drug delivery. PMID:26951462

Abuse-resistant drug delivery.

PubMed

DuPont, Robert L; Bensinger, Peter B

2006-08-01

In attempting to reduce the nonmedical use of controlled substances, a reasonable step is to educate the physicians prescribing controlled substances, including the prescription stimulants used to treat ADHD, as well as patients and family members, about the risks of nonmedical use and the dangers of giving or selling these medicines to persons for whom they were not prescribed. Patients who find benefits in the use of such medicines have a significant interest in protecting their continued access to them. Such access is potentially threatened by concerns about widespread nonmedical use. Physicians can help protect the appropriate medical use of prescription stimulants by considering the abuse potential of various medicines used to treat patients with ADHD, especially when these patients also have a history of nonmedical substance use. In addition, we suggest that today there is an opportunity to add a new and perhaps more hopeful paradigm: the wider use of drug delivery systems that make products less attractive to drug abusers. This new drug abuse prevention paradigm holds great promise for efforts to reduce the nonmedical use of prescription controlled substances, including the prescription stimulants used to treat ADHD. To achieve the full potential of this new paradigm to reduce prescription drug abuse, it will be necessary to develop standards to assess the relative abuse resistance of various drug formulations and delivery systems, as well as meaningful incentives to foster the development of these abuse-resistant delivery systems for controlled substances.

Elastin-Like Recombinamers As Smart Drug Delivery Systems.

PubMed

Arias, F Javier; Santos, Mercedes; Ibanez-Fonseca, Arturo; Pina, Maria Jesus; Serrano, Sofía

2018-02-19

Drug delivery systems that are able to control the release of bioactive molecules and designed to carry drugs to target sites are of particular interest for tissue therapy. Moreover, systems comprising materials that can respond to environmental stimuli and promote self-assembly and higher order supramolecular organization are especially useful in the biomedical field. Objetive: This review focuses on biomaterials suitable for this purpose and that include elastin-like recombinamers (ELRs), a class of proteinaceous polymers bioinspired by natural elastin, designed using recombinant technologies. The self-assembly and thermoresponsive behaviour of these systems, along with their biodegradability, biocompatibility and well-defined composition as a result of their tailormade design, make them particularly attractive for controlled drug delivery. ELR-based delivery systems that allow targeted delivery are reviewed, especially ELR-drug recombinant fusion constructs, ELR-drug systems chemically bioconjugated in their monomeric and soluble forms, and drug encapsulation by nanoparticle-forming ELRs. Subsequently, the review focuses on those drug carriers in which smart release is triggered by pH or temperature with a particular focus on cancer treatments. Systems for controlled drug release based on depots and hydrogels that act as both a support and reservoir in which drugs can be stored will be described, and their applications in drug delivery discussed. Finally, smart drug-delivery systems not based on ELRs, including those comprising proteins, synthetic polymers and non-polymeric systems, will also be briefly discussed. Several different constructions based on ELRs are potential candidates for controlled drug delivery to be applied in advanced biomedical treatments. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Local Drug Delivery to Prevent Restenosis

PubMed Central

Seedial, Stephen M.; Ghosh, Soumojit; Saunders, R. Scott; Suwanabol, Pasithorn A.; Shi, Xudong; Liu, Bo; Kent, K. Craig

2013-01-01

Introduction Despite significant advances in vascular biology, bioengineering and pharmacology, restenosis remains a limitation to the overall efficacy of vascular reconstructions, both percutaneous and open. Although the pathophysiology of intimal hyperplasia is complex, a number of drugs and/or molecular tools have been identified that can prevent restenosis. Moreover, the focal nature of this process lends itself to treatment with local drug administration. In this article we provide a broad overview of current and future techniques for local drug delivery that have been developed to prevent restenosis following vascular intervention. Methods A systematic electronic literature search using PubMed was performed for all accessible published articles through September 2012. In an effort to remain current, additional searches were performed for abstracts presented at relevant societal meetings, filed patents, clinical trials and funded NIH awards. Results The efficacy of local drug delivery has been demonstrated in the coronary circulation with the current clinical use of drug-eluting stents (DES). Until recently, however, DES were not found to be efficacious in the peripheral circulation. Further pursuit of intraluminal devices has led to the development of balloon-based technologies with a recent surge in trials involving drug-eluting balloons. Early data appears encouraging, particularly for treatment of lesions in the superficial femoral artery, with several devices having recently received the CE mark in Europe. Investigators have also explored periadventitial application of biomaterials containing anti-restenotic drugs, an approach that could be particularly useful for surgical bypass or endarterectomy. In the past systemic drug delivery has been unsuccessful, however, there has been recent exploration of intravenous delivery of drugs designed specifically to target injured or reconstructed arteries. Our review revealed a multitude of additional interesting

Photoacoustic microscopy imaging for microneedle drug delivery

NASA Astrophysics Data System (ADS)

Moothanchery, Mohesh; Seeni, Razina Z.; Xu, Chenjie; Pramanik, Manojit

2018-02-01

The recent development of novel transdermal drug delivery systems (TDDS) using microneedle technology allows micron-sized conduits to be formed within the outermost skin layers attracting keen interest in skin as an interface for localized and systemic delivery of therapeutics. In light of this, researchers are using microneedles as tools to deliver nanoparticle formulations to targeted sites for effective therapy. However, in such studies the use of traditional histological methods are employed for characterization and do not allow for the in vivo visualization of drug delivery mechanism. Hence, this study presents a novel imaging technology to characterize microneedle based nanoparticle delivery systems using optical resolution-photoacoustic microscopy (OR-PAM). In this study in vivo transdermal delivery of gold nanoparticles using microneedles in mice ear and the spatial distribution of the nanoparticles in the tissue was successfully illustrated. Characterization of parameters that are relevant in drug delivery studies such as penetration depth, efficiency of delivered gold nanoparticles were monitored using the system. Photoacoustic microscopy proves an ideal tool for the characterization studies of microneedle properties and the studies shows microneedles as an ideal tool for precise and controlled drug delivery.

Advancements in the delivery of epigenetic drugs

PubMed Central

Cramer, Samantha A.; Adjei, Isaac M.; Labhasetwar, Vinod

2015-01-01

Introduction Advancements in epigenetic treatments are not only coming from new drugs but from modifications or encapsulation of the existing drugs into different formulations leading to greater stability and enhanced delivery to the target site. The epigenome is highly regulated and complex; therefore it is important that off-target effects of epigenetic drugs be minimized. The step from in vitro to in vivo treatment of these drugs often requires development of a method of effective delivery for clinical translation. Areas covered This review covers epigenetic mechanisms such as DNA methylation, chromatin remodeling and small RNA mediated gene regulation. There is a section in the review with examples of diseases where epigenetic alterations lead to impaired pathways, with an emphasis on cancer. Epigenetic drugs, their targets and clinical status are presented. Advantages of using a delivery method for epigenetic drugs as well as examples of current advancements and challenges are also discussed. Expert opinion Epigenetic drugs have the potential to be very effective therapy against a number of diseases, especially cancers and neurological disorders. As with many chemotherapeutics, undesired side effects need to be minimized. Finding a suitable delivery method means reducing side effects and achieving a higher therapeutic index. Each drug may require a unique delivery method exploiting the drug's chemistry or other physical characteristic requiring interdisciplinary participation and would benefit from a better understanding of the mechanisms of action. PMID:25739728

Engineering a degradable polyurethane intravaginal ring for sustained delivery of dapivirine.

PubMed

Kaur, Manpreet; Gupta, Kavita M; Poursaid, Azadeh E; Karra, Prasoona; Mahalingam, Alamelu; Aliyar, Hyder A; Kiser, Patrick F

2011-06-01

We describe the engineering of a degradable intravaginal ring (IVR) for the delivery of the potent HIV-1 reverse transcriptase inhibitor dapivirine. The degradable polymer used in fabricating the device incorporated poly(caprolactone) ester blocks in a poly(tetramethylene ether) glycol ABA type polyurethane backbone. The polymer was designed to maintain its structure for 1 month during usage and then degrade in the environment post-disposal. In vitro release of dapivirine showed zero-order kinetics for up to 1 month and significant levels of drug release into engineered vaginal tissue. The mechanical properties of the degradable IVR were comparable to those of a widely used contraceptive intravaginal ring upon exposure to simulated vaginal conditions. Incubation under simulated vaginal conditions for a month caused minimal degradation with minimal effect on the mechanical properties of the ring and polymer. The cytotoxicity evaluation of the drug-loaded IVRs against Vk2/E6E7 human vaginal epithelial cells, Lactobacillus jensenii, and engineered vaginal tissue constructs showed the degradable polyurethane to be non-toxic. In vitro evaluation of inflammatory potential monitored through the levels of inflammatory cytokines IL-8, IL-1α, IL-6, IL-1β, and MIP-3α when engineered EpiVaginal™ tissue was incubated with the polyurethanes suggested that the degradable polyurethane was comparable to commercial medical grade polyurethane. These results are encouraging for further development of this degradable IVR for topical vaginal delivery of microbicides.

pH and temperature dual-sensitive liposome gel based on novel cleavable mPEG-Hz-CHEMS polymeric vaginal delivery system

PubMed Central

Chen, Daquan; Sun, Kaoxiang; Mu, Hongjie; Tang, Mingtan; Liang, Rongcai; Wang, Aiping; Zhou, Shasha; Sun, Haijun; Zhao, Feng; Yao, Jianwen; Liu, Wanhui

2012-01-01

Background In this study, a pH and temperature dual-sensitive liposome gel based on a novel cleavable hydrazone-based pH-sensitive methoxy polyethylene glycol 2000-hydrazone-cholesteryl hemisuccinate (mPEG-Hz-CHEMS) polymer was used for vaginal administration. Methods The pH-sensitive, cleavable mPEG-Hz-CHEMS was designed as a modified pH-sensitive liposome that would selectively degrade under locally acidic vaginal conditions. The novel pH-sensitive liposome was engineered to form a thermogel at body temperature and to degrade in an acidic environment. Results A dual-sensitive liposome gel with a high encapsulation efficiency of arctigenin was formed and improved the solubility of arctigenin characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry. The dual-sensitive liposome gel with a sol-gel transition at body temperature was degraded in a pH-dependent manner, and was stable for a long period of time at neutral and basic pH, but cleavable under acidic conditions (pH 5.0). Arctigenin encapsulated in a dual-sensitive liposome gel was more stable and less toxic than arctigenin loaded into pH-sensitive liposomes. In vitro drug release results indicated that dual-sensitive liposome gels showed constant release of arctigenin over 3 days, but showed sustained release of arctigenin in buffers at pH 7.4 and pH 9.0. Conclusion This research has shed some light on a pH and temperature dual-sensitive liposome gel using a cleavable mPEG-Hz-CHEMS polymer for vaginal delivery. PMID:22679372

Polymer nanogels: a versatile nanoscopic drug delivery platform

PubMed Central

Chacko, Reuben T.; Ventura, Judy; Zhuang, Jiaming; Thayumanavan, S.

2012-01-01

In this review we put the spotlight on crosslinked polymer nanogels, a promising platform that has the characteristics of an “ideal” drug delivery vehicle. Some of the key aspects of drug delivery vehicle design like stability, response to biologically relevant stimuli, passive targeting, active targeting, toxicity and ease of synthesis are discussed. We discuss several delivery systems in this light and highlight some examples of systems, which satisfy some or all of these design requirements. In particular, we point to the advantages that crosslinked polymeric systems bring to drug delivery. We review some of the synthetic methods of nanogel synthesis and conclude with the diverse applications in drug delivery where nanogels have been fruitfully employed. PMID:22342438

Porous Carriers for Controlled/Modulated Drug Delivery

PubMed Central

Ahuja, G.; Pathak, K.

2009-01-01

Considerable research efforts have been directed in recent years towards the development of porous carriers as controlled drug delivery matrices because of possessing several features such as stable uniform porous structure, high surface area, tunable pore size and well-defined surface properties. Owing to wide range of useful properties porous carriers have been used in pharmaceuticals for many purposes including development of floating drug delivery systems, sustained drug delivery systems. Various types of pores like open, closed, transport and blind pores in the porous solid allow them to adsorb drugs and release them in a more reproducible and predictable manner. Pharmaceutically exploited porous adsorbents includes, silica (mesoporous), ethylene vinyl acetate (macroporous), polypropylene foam powder (microporous), titanium dioxide (nanoporous). When porous polymeric drug delivery system is placed in contact with appropriate dissolution medium, release of drug to medium must be preceded by the drug dissolution in the water filled pores or from surface and by diffusion through the water filled channels. The porous carriers are used to improve the oral bioavailability of poorly water soluble drugs, to increase the dissolution of relatively insoluble powders and conversion of crystalline state to amorphous state. PMID:20376211

Microneedles for drug and vaccine delivery

PubMed Central

Kim, Yeu-Chun; Park, Jung-Hwan; Prausnitz, Mark R.

2012-01-01

Microneedles were first conceptualized for drug delivery many decades ago, but only became the subject of significant research starting in the mid-1990’s when microfabrication technology enabled their manufacture as (i) solid microneedles for skin pretreatment to increase skin permeability, (ii) microneedles coated with drug that dissolves off in the skin, (iii) polymer microneedles that encapsulate drug and fully dissolve in the skin and (iv) hollow microneedles for drug infusion into the skin. As shown in more than 350 papers now published in the field, microneedles have been used to deliver a broad range of different low molecular weight drugs, biotherapeutics and vaccines, including published human studies with a number of small-molecule and protein drugs and vaccines. Influenza vaccination using a hollow microneedle is in widespread clinical use and a number of solid microneedle products are sold for cosmetic purposes. In addition to applications in the skin, microneedles have also been adapted for delivery of bioactives into the eye and into cells. Successful application of microneedles depends on device function that facilitates microneedle insertion and possible infusion into skin, skin recovery after microneedle removal, and drug stability during manufacturing, storage and delivery, and on patient outcomes, including lack of pain, skin irritation and skin infection, in addition to drug efficacy and safety. Building off a strong technology base and multiple demonstrations of successful drug delivery, microneedles are poised to advance further into clinical practice to enable better pharmaceutical therapies, vaccination and other applications. PMID:22575858

Inorganic Nanomaterials as Carriers for Drug Delivery.

PubMed

Chen, Shizhu; Hao, Xiaohong; Liang, Xingjie; Zhang, Qun; Zhang, Cuimiao; Zhou, Guoqiang; Shen, Shigang; Jia, Guang; Zhang, Jinchao

2016-01-01

For safe and effective therapy, drugs must be delivered efficiently and with minimal systemic side effects. Nanostructured drug carriers enable the delivery of small-molecule drugs as well as nucleic acids and proteins. Inorganic nanomaterials are ideal for drug delivery platforms due to their unique physicochemical properties, such as facile preparation, good storage stability and biocompatibility. Many inorganic nanostructure-based drug delivery platforms have been prepared. Although there are still many obstacles to overcome, significant advances have been made in recent years. This review focuses on the status and development of inorganic nanostructures, including silica, quantum dots, gold, carbon-based and magnetic iron oxide-based nanostructures, as carriers for chemical and biological drugs. We specifically highlight the extensive use of these inorganic drug carriers for cancer therapy. Finally, we discuss the most important areas in the field that urgently require further study.

Clinical Factors Associated With Presentation Change of the Second Twin After Vaginal Delivery of the First Twin.

PubMed

Panelli, Danielle M; Easter, Sarah Rae; Bibbo, Carolina; Robinson, Julian N; Carusi, Daniela A

2017-11-01

To identify clinical factors associated with a change from vertex to nonvertex presentation in the second twin after vaginal birth of the first. We assembled a retrospective cohort of women with viable vertex-vertex twin pregnancies who delivered the presenting twin vaginally. Women whose second twin changed from vertex to nonvertex after vaginal birth of the first were classified as experiencing an intrapartum change in presentation. Characteristics associated with intrapartum presentation change in a univariate analysis with a P value ≤.10 were then evaluated in a multivariate logistic regression model. Four-hundred fifty women met inclusion criteria, of whom 55 (12%) had intrapartum presentation change of the second twin. Women experiencing intrapartum presentation change were more likely to be multiparous (69% compared with 47%, P<.01) and to have had a change in the presentation of the second twin between the most recent antepartum ultrasonogram and the ultrasonogram done on admission to labor and delivery (11% compared with 4%, P=.04). In an adjusted analysis, multiparity and gestational age less than 34 weeks were significantly associated with presentation change (adjusted odds ratio [OR] 2.9, 95% CI 1.5-5.6 and adjusted OR 2.6, 95% CI 1.1-5.9, respectively). Women with intrapartum presentation change were more likely to undergo cesarean delivery for their second twin (44% compared with 7%, P<.01) with an adjusted OR of 10.50 (95% CI 5.20-21.20) compared with those with stable intrapartum presentation. Twenty of the 24 (83%) cesarean deliveries performed in the intrapartum presentation change group were done for issues related to malpresentation. Multiparity and gestational age less than 34 weeks are associated with intrapartum presentation change of the second twin.

Drug delivery with microsecond laser pulses into gelatin.

PubMed

Shangguan, H; Casperson, L W; Shearin, A; Gregory, K W; Prahl, S A

1996-07-01

Photo acoustic drug delivery is a technique for localized drug delivery by laser-induced hydrodynamic pressure following cavitation bubble expansion and collapse. Photoacoustic drug delivery was investigated on gelatin-based thrombus models with planar and cylindrical geometries by use of one microsecond laser pulses. Solutions of a hydrophobic dye in mineral oil permitted monitoring of delivered colored oil into clear gelatin-based thrombus models. Cavitation bubble development and photoacoustic drug delivery were visualized with flash photography. This study demonstrated that cavitation is the governing mechanism for photoacoustic drug delivery, and the deepest penetration of colored oil in gels followed the bubble collapse. Spatial distribution measurements revealed that colored oil could be driven a few millimeters into the gels in both axial and radial directions, and the penetration was less than 500 µm when the gelatin structure was not fractured.

Contact-facilitated drug delivery with Sn2 lipase labile prodrugs optimize targeted lipid nanoparticle drug delivery.

PubMed

Pan, Dipanjan; Pham, Christine T N; Weilbaecher, Katherine N; Tomasson, Michael H; Wickline, Samuel A; Lanza, Gregory M

2016-01-01

Sn2 lipase labile phospholipid prodrugs in conjunction with contact-facilitated drug delivery offer an important advancement in Nanomedicine. Many drugs incorporated into nanosystems, targeted or not, are substantially lost during circulation to the target. However, favorably altering the pharmacokinetics and volume of distribution of systemic drug delivery can offer greater efficacy with lower toxicity, leading to new prolonged-release nanoexcipients. However, the concept of achieving Paul Erhlich's inspired vision of a 'magic bullet' to treat disease has been largely unrealized due to unstable nanomedicines, nanosystems achieving low drug delivery to target cells, poor intracellular bioavailability of endocytosed nanoparticle payloads, and the substantial biological barriers of extravascular particle penetration into pathological sites. As shown here, Sn2 phospholipid prodrugs in conjunction with contact-facilitated drug delivery prevent premature drug diffusional loss during circulation and increase target cell bioavailability. The Sn2 phospholipid prodrug approach applies equally well for vascular constrained lipid-encapsulated particles and micelles the size of proteins that penetrate through naturally fenestrated endothelium in the bone marrow or thin-walled venules of an inflamed microcirculation. At one time Nanomedicine was considered a 'Grail Quest' by its loyal opposition and even many in the field adsorbing the pains of a long-learning curve about human biology and particles. However, Nanomedicine with innovations like Sn2 phospholipid prodrugs has finally made 'made the turn' toward meaningful translational success. © 2015 The Authors. WIREs Nanomedicine and Nanobiotechnology published by Wiley Periodicals, Inc.

Contact-facilitated drug delivery with Sn2 lipase labile prodrugs optimize targeted lipid nanoparticle drug delivery

PubMed Central

Pan, Dipanjan; Pham, Christine TN; Weilbaecher, Katherine N; Tomasson, Michael H; Wickline, Samuel A; Lanza, Gregory M

2016-01-01

Sn2 lipase labile phospholipid prodrugs in conjunction with contact-facilitated drug delivery offer an important advancement in Nanomedicine. Many drugs incorporated into nanosystems, targeted or not, are substantially lost during circulation to the target. However, favorably altering the pharmacokinetics and volume of distribution of systemic drug delivery can offer greater efficacy with lower toxicity, leading to new prolonged-release nanoexcipients. However, the concept of achieving Paul Erhlich's inspired vision of a ‘magic bullet’ to treat disease has been largely unrealized due to unstable nanomedicines, nanosystems achieving low drug delivery to target cells, poor intracellular bioavailability of endocytosed nanoparticle payloads, and the substantial biological barriers of extravascular particle penetration into pathological sites. As shown here, Sn2 phospholipid prodrugs in conjunction with contact-facilitated drug delivery prevent premature drug diffusional loss during circulation and increase target cell bioavailability. The Sn2 phospholipid prodrug approach applies equally well for vascular constrained lipid-encapsulated particles and micelles the size of proteins that penetrate through naturally fenestrated endothelium in the bone marrow or thin-walled venules of an inflamed microcirculation. At one time Nanomedicine was considered a ‘Grail Quest’ by its loyal opposition and even many in the field adsorbing the pains of a long-learning curve about human biology and particles. However, Nanomedicine with innovations like Sn2 phospholipid prodrugs has finally made ‘made the turn’ toward meaningful translational success. PMID:26296541

Development of polylactide and polyethylene vinyl acetate blends for the manufacture of vaginal rings.

PubMed

Mc Conville, Christopher; Major, Ian; Friend, David R; Clark, Meredith R; Woolfson, A David; Malcolm, R Karl

2012-05-01

Vaginal rings are currently being investigated for delivery of HIV microbicides. However, vaginal rings are currently manufactured form hydrophobic polymers such as silicone elastomer and polyethylene vinyl acetate (PEVA), which do not permit release of hydrophilic microbicides such as the nucleotide reverse transcriptase inhibitor tenofovir. Biodegradable polymers such as polylactide (PLA) may help increase release rates by controlling polymer degradation rather than diffusion of the drug through the polymer. However, biodegradable polymers have limited flexibility making them unsuitable for use in the manufacture of vaginal rings. This study demonstrates that by blending PLA and PEVA together it is possible to achieve a blend that has flexibility similar to native PEVA but also allows for the release of tenofovir. Copyright © 2011 Wiley Periodicals, Inc.

Targeted Vascular Drug Delivery in Cerebral Cancer.

PubMed

Humle, Nanna; Johnsen, Kasper Bendix; Arendt, Gitte Abildgaard; Nielsen, Rikke Paludan; Moos, Torben; Thomsen, Louiza Bohn

2016-01-01

This review presents the present-day literature on the anatomy and physiological mechanisms of the blood-brain barrier and the problematic of cerebral drug delivery in relation to malignant brain tumors. First step in treatment of malignant brain tumors is resection, but there is a high risk of single remnant infiltrative tumor cells in the outer zone of the brain tumor. These infiltrative single-cells will be supplied by capillaries with an intact BBB as opposed to the partly leaky BBB found in the tumor tissue before resection. Even though BBB penetrance of a chemotherapeutic agent is considered irrelevant though the limited success rate for chemotherapeutic treatability of GBM tumors indicate otherwise. Therefore drug delivery strategies to cerebral cancer after resection should be tailored to being able to both penetrate the intact BBB and target the cancer cells. In this review the intact bloodbrain barrier and cerebral cancer with main focus on glioblastoma multiforme (GBM) is introduced. The GBM induced formation of a blood-tumor barrier and the consequences hereof is described and discussed with emphasis on the impact these changes of the BBB has on drug delivery to GBM. The most commonly used drug carriers for drug delivery to GBM is described and the current drug delivery strategies for glioblastoma multiforme including possible routes through the BBB and epitopes, which can be targeted on the GBM cells is outlined. Overall, this review aims to address targeted drug delivery in GBM treatment when taking the differing permeability of the BBB into consideration.

A pulsed mode electrolytic drug delivery device

NASA Astrophysics Data System (ADS)

Yi, Ying; Buttner, Ulrich; Carreno, Armando A. A.; Conchouso, David; Foulds, Ian G.

2015-10-01

This paper reports the design of a proof-of-concept drug delivery device that is actuated using the bubbles formed during electrolysis. The device uses a platinum (Pt) coated nickel (Ni) metal foam and a solid drug in reservoir (SDR) approach to improve the device’s performance. This electrochemically-driven pump has many features that are unlike conventional drug delivery devices: it is capable of pumping periodically and being refilled automatically; it features drug release control; and it enables targeted delivery. Pt-coated metal foam is used as a catalytic reforming element, which reduces the period of each delivery cycle. Two methods were used for fabricating the Pt-coated metal: sputtering and electroplating. Of these two methods, the sputtered Pt-coated metal foam has a higher pumping rate; it also has a comparable recombination rate when compared to the electroplated Pt-coated metal foam. The only drawback of this catalytic reformer is that it consumes nickel scaffold. Considering long-term applications, the electroplated Pt metal foam was selected for drug delivery, where a controlled drug release rate of 2.2 μg  ±  0.3 μg per actuation pulse was achieved using 4 mW of power.

Vaginal preparation with antiseptic solution before cesarean section for preventing postoperative infections.

PubMed

Haas, David M; Morgan, Sarah; Contreras, Karenrose

2014-12-21

Cesarean delivery is one of the most common surgical procedures performed by obstetricians. Infectious morbidity after cesarean delivery can have a tremendous impact on the postpartum woman's return to normal function and her ability to care for her baby. Despite the widespread use of prophylactic antibiotics, postoperative infectious morbidity still complicates cesarean deliveries. To determine if cleansing the vagina with an antiseptic solution before a cesarean delivery decreases the risk of maternal infectious morbidities, including endometritis and wound complications. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (10 December 2014). We included randomized and quasi-randomized trials assessing the impact of vaginal cleansing immediately before cesarean delivery with any type of antiseptic solution versus a placebo solution/standard of care on post-cesarean infectious morbidity. We independently assessed eligibility and quality of the studies. Seven trials randomizing 2816 women (2635 analyzed) evaluated the effects of vaginal cleansing (all with povidone-iodine) on post-cesarean infectious morbidity. The risk of bias was generally low, with the quality of most of the studies being high. Vaginal preparation immediately before cesarean delivery significantly reduced the incidence of post-cesarean endometritis from 8.3% in control groups to 4.3% in vaginal cleansing groups (average risk ratio (RR) 0.45, 95% confidence interval (CI) 0.25 to 0.81, seven trials, 2635 women). The risk reduction was particularly strong for women who were already in labor at the time of the cesarean delivery (7.4% in the vaginal cleansing group versus 13.0% in the control group; RR 0.56, 95% CI 0.34 to 0.95, three trials, 523 women) and for women with ruptured membranes (4.3% in the vaginal cleansing group versus 17.9% in the control group; RR 0.24, 95% CI 0.10 to 0.55, three trials, 272 women). No other outcomes realized statistically significant

21 CFR 884.3900 - Vaginal stent.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Vaginal stent. 884.3900 Section 884.3900 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES... stent. (a) Identification. A vaginal stent is a device used to enlarge the vagina by stretching, or to...

Drug self-delivery systems for cancer therapy.

PubMed

Qin, Si-Yong; Zhang, Ai-Qing; Cheng, Si-Xue; Rong, Lei; Zhang, Xian-Zheng

2017-01-01

Carrier-assistant drug delivery systems (DDSs) have been rapidly established for cancer therapy and great strides have been made in recent years. However, further development of DDSs is retarded by the aspects such as the low drug carrying capacity, carrier-induced toxicity and immunogenicity, complex synthesis manipulation. Drug self-delivery systems (DSDSs), in which active drugs exhibit nanoscale characteristic to realize intracellular delivery by themselves without the help of nanocarriers, have been rapidly developed to address these issues. In this review, we present a comprehensive summary of the recent advances in DSDSs for cancer therapy. After a brief introduction to the major types of DSDSs and their fabrication strategies, we emphatically discuss some representative achievements of these DSDSs for passive or/and positive targeting therapy, combinational therapy as well as theranostics. The design principle is explained and justified, which can cast a new light on developing drug delivery systems for cancer treatments. Copyright © 2016 Elsevier Ltd. All rights reserved.

Postpartum anal sphincter lacerations in a population with minimal exposure to episiotomy and operative vaginal delivery.

PubMed

Lewis, Cindi; Williams, Alana M; Rogers, Rebecca G

2008-01-01

This case-control study was designed to identify risk factors for anal sphincter lacerations (ASL) in a multicultural population where episiotomies and operative vaginal deliveries are rarely performed. Cases were subjects with ASL delivered between July 1997 and June 2003. Two controls were selected for each case matched for gestational age. Independent variables collected included age, race/ethnicity, parity, tobacco use, medical conditions, episiotomy, operative vaginal delivery, epidural use, and infant weight. One thousand and sixty-six subjects met the inclusion criteria. The risk of ASL increased with increasing maternal age (Odds ratio [OR] 1.09 per year, 95% confidence interval [CI] 1.06, 1.12) and increasing infant weight (OR 1.09 per 100 g, 95% CI 1.06, 1.13). Multiparity was protective (P1 vs P2 OR 0.19, 95% CI 0.13, 0.28, and > or =P3 vs P1 OR 0.04, 95% CI 0.02, 0.11). Hispanic and Native American women were at increased risk for ASL (OR 2.08, 95% CI 1.41, 3.09 and OR 1.92, 95% CI 1.07, 3.45, respectively).

Current Strategies for Brain Drug Delivery

PubMed Central

Dong, Xiaowei

2018-01-01

The blood-brain barrier (BBB) has been a great hurdle for brain drug delivery. The BBB in healthy brain is a diffusion barrier essential for protecting normal brain function by impeding most compounds from transiting from the blood to the brain; only small molecules can cross the BBB. Under certain pathological conditions of diseases such as stroke, diabetes, seizures, multiple sclerosis, Parkinson's disease and Alzheimer disease, the BBB is disrupted. The objective of this review is to provide a broad overview on current strategies for brain drug delivery and related subjects from the past five years. It is hoped that this review could inspire readers to discover possible approaches to deliver drugs into the brain. After an initial overview of the BBB structure and function in both healthy and pathological conditions, this review re-visits, according to recent publications, some questions that are controversial, such as whether nanoparticles by themselves could cross the BBB and whether drugs are specifically transferred to the brain by actively targeted nanoparticles. Current non-nanoparticle strategies are also reviewed, such as delivery of drugs through the permeable BBB under pathological conditions and using non-invasive techniques to enhance brain drug uptake. Finally, one particular area that is often neglected in brain drug delivery is the influence of aging on the BBB, which is captured in this review based on the limited studies in the literature. PMID:29556336

Drug Delivery of the Future: Chasing the Invisible Gorilla

PubMed Central

Park, Kinam

2015-01-01

For more than 60 years drug delivery systems have produced numerous controlled release formulations helping patients improve compliance and maximize the drug efficacy. Development of new controlled drug delivery systems was very productive during the period 1950-1980. The productivity, as measured by the number of clinically used formulations, dropped significantly during 1980-2010. This reduced productivity needs to be understood so that the future development of drug delivery systems can be accelerated and prolific again. This requires critical evaluation of the current drug delivery field, so that the factors inhibiting rapid progress can be identified and resolved. The current drug delivery field is faced with an invisible gorilla syndrome, i.e., seeing a gorilla when it is not present and missing a gorilla when it actually exists. Overcoming this syndrome requires a new way of thinking, questioning the status quo. Advances in drug delivery technologies occur by an evolutionary process, and thus, the more trials and errors lead to faster advances. The drug delivery area needs to nurture the environment where vastly different ideas can be tested, and all data, positive or negative, need to be exchanged freely as they have equal importance. PMID:26519857

Inhaled nano- and microparticles for drug delivery

PubMed Central

El-Sherbiny, Ibrahim M.; El-Baz, Nancy M.; Yacoub, Magdi H.

2015-01-01

The 21st century has seen a paradigm shift to inhaled therapy, for both systemic and local drug delivery, due to the lung's favourable properties of a large surface area and high permeability. Pulmonary drug delivery possesses many advantages, including non-invasive route of administration, low metabolic activity, control environment for systemic absorption and avoids first bypass metabolism. However, because the lung is one of the major ports of entry, it has multiple clearance mechanisms, which prevent foreign particles from entering the body. Although these clearance mechanisms maintain the sterility of the lung, clearance mechanisms can also act as barriers to the therapeutic effectiveness of inhaled drugs. This effectiveness is also influenced by the deposition site and delivered dose. Particulate-based drug delivery systems have emerged as an innovative and promising alternative to conventional inhaled drugs to circumvent pulmonary clearance mechanisms and provide enhanced therapeutic efficiency and controlled drug release. The principle of multiple pulmonary clearance mechanisms is reviewed, including mucociliary, alveolar macrophages, absorptive, and metabolic degradation. This review also discusses the current approaches and formulations developed to achieve optimal pulmonary drug delivery systems. PMID:26779496

Quantitative analyses of variability in normal vaginal shape and dimension on MR images

PubMed Central

Luo, Jiajia; Betschart, Cornelia; Ashton-Miller, James A.; DeLancey, John O. L.

2016-01-01

Introduction and hypothesis We present a technique for quantifying inter-individual variability in normal vaginal shape, axis, and dimension, and report findings in healthy women. Methods Eighty women (age: 28~70 years) with normal pelvic organ support underwent supine, multi-planar proton-density MRI. Vaginal width was assessed at five evenly-spaced locations, and vaginal axis, length, and surface area were quantified via ImageJ and MATLAB. Results The mid-sagittal plane angles, relative to the horizontal, of three vaginal axes were 90± 11, 72± 21, and 41± 22° (caudal to cranial, p < 0.001). The mean (± SD) vaginal widths were 17± 5, 24± 4, 30± 7, 41± 9, and 45± 12 mm at the five locations (caudal to cranial, p < 0.001). Mid-sagittal lengths for anterior and posterior vaginal walls were 63± 9 and 98 ± 18 mm respectively. The vaginal surface area was 72 ± 21 cm2 (range: 34 ~ 164 cm2). The coefficient of determination between any demographic variable and any vaginal dimension did not exceed 0.16. Conclusions Large variations in normal vaginal shape, axis, and dimensions were not explained by body size or other demographic variables. This variation has implications for reconstructive surgery, intravaginal and surgical product design, and vaginal drug delivery. PMID:26811115

Inner Ear Drug Delivery for Auditory Applications

PubMed Central

Swan, Erin E. Leary; Mescher, Mark J.; Sewell, William F.; Tao, Sarah L.; Borenstein, Jeffrey T.

2008-01-01

Many inner ear disorders cannot be adequately treated by systemic drug delivery. A blood-cochlear barrier exists, similar physiologically to the blood-brain barrier, which limits the concentration and size of molecules able to leave the circulation and gain access to the cells of the inner ear. However, research in novel therapeutics and delivery systems has led to significant progress in the development of local methods of drug delivery to the inner ear. Intratympanic approaches, which deliver therapeutics to the middle ear, rely on permeation through tissue for access to the structures of the inner ear, whereas intracochlear methods are able to directly insert drugs into the inner ear. Innovative drug delivery systems to treat various inner ear ailments such as ototoxicity, sudden sensorineural hearing loss, autoimmune inner ear disease, and for preserving neurons and regenerating sensory cells are being explored. PMID:18848590

Development of a gastroretentive pulsatile drug delivery platform.

PubMed

Thitinan, Sumalee; McConville, Jason T

2012-04-01

To develop a novel gastroretentive pulsatile drug delivery platform by combining the advantages of floating dosage forms for the stomach and pulsatile drug delivery systems. A gastric fluid impermeable capsule body was used as a vessel to contain one or more drug layer(s) as well as one or more lag-time controlling layer(s). A controlled amount of air was sealed in the innermost portion of the capsule body to reduce the overall density of the drug delivery platform, enabling gastric floatation. An optimal mass fill inside the gastric fluid impermeable capsule body enabled buoyancy in a vertical orientation to provide a constant surface area for controlled erosion of the lag-time controlling layer. The lag-time controlling layer consisted of a swellable polymer, which rapidly formed a gel to seal the mouth of capsule body and act as a barrier to gastric fluid ingress. By varying the composition of the lag-time controlling layer, it was possible to selectively program the onset of the pulsatile delivery of a drug. This new delivery platform offers a new method of delivery for a variety of suitable drugs targeted in chronopharmaceutical therapy. This strategy could ultimately improve drug efficacy and patient compliance, and reduce harmful side effects by scaling back doses of drug administered. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

Development In Drug Targeting And Delivery In Cervical Cancer.

PubMed

Aggarwal, Urvashi; Goyal, Amit Kumar; Rath, Goutam

2017-10-09

Cervical cancer is the second most common cancer in women. Standard treatment options available for cervical cancer including chemotherapy, surgery and radiation therapy associated with their own side effects and toxicities. Tumor-targeted delivery of anticancer drugs is perhaps one of the most appropriate strategies to achieve optimal outcomes from treatment and improve quality of life. Recently nanocarriers based drug delivery systems owing to their unique properties have been extensively investigated for anticancer drug delivery. In addition to that addressing the anatomical significance of cervical cancer, various local drug delivery strategies for the cancer treatment are introduced like: gels, nanoparticles, polymeric films, rods and wafers, lipid based nanocarrier. Localized drug delivery systems allows passive drug targeting results in high drug concentration at the target site. Further they can be tailor made to achieve both sustained and controlled release behavior, substantially improving therapeutic outcomes and minimizing side effects. This review summarizes the meaningful advances in drug delivery strategies to treat cervical cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Conservative Management of Placenta Accreta/Increta after Vaginal Birth

PubMed Central

Peiffer, S.; Reinhard, J.; Reitter, A.; Louwen, F.

2012-01-01

Aim: Aim of the study was to show that conservative management with preservation of the uterus and of fertility is possible in patients with placenta accreta/increta after vaginal delivery. Method: A retrospective analysis of patients with placental attachment disorders after vaginal delivery was done in a perinatal centre between November 2009 and April 2011. The patient collective was identified using the ICD-10 codes for placenta accreta/increta/percreta, and patient records were analysed for risk factors, maternal morbidity, preservation of the uterus and of fertility, and neonatal outcome. Results: Three cases of placenta increta were identified in the last 1.5 years out of a total of 1457 vaginal deliveries, and all 3 cases were treated conservatively. Mean maternal age was 35.3 years; gestational age ranged from 39 to 41 weeks, and mean duration between delivery of the child and delivery of the placenta was 44.67 days (range: 14–100 days). Two patients developed symptoms of endomyometritis, including fever, leukocytosis and increased CRP levels. All 3 women were successfully managed with preservation of the uterus. Conclusion: In selected cases with placenta accreta/increta after vaginal delivery, it is possible to avoid surgical procedures, particularly hysterectomy procedures, and successfully manage these patients conservatively with preservation of the uterus. PMID:25308979

Vaginal preparation with antiseptic solution before cesarean section for preventing postoperative infections.

PubMed

Haas, David M; Morgan, Sarah; Contreras, Karenrose

2014-09-09

Cesarean delivery is one of the most common surgical procedures performed by obstetricians. Infectious morbidity after cesarean delivery can have a tremendous impact on the postpartum woman's return to normal function and her ability to care for her baby. Despite the widespread use of prophylactic antibiotics, postoperative infectious morbidity still complicates cesarean deliveries. To determine if cleansing the vagina with an antiseptic solution before a cesarean delivery decreases the risk of maternal infectious morbidities, including endometritis and wound complications. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (21 July 2014). We included randomized and quasi-randomized trials assessing the impact of vaginal cleansing immediately before cesarean delivery with any type of antiseptic solution versus a placebo solution/standard of care on post-cesarean infectious morbidity. We independently assessed eligibility and quality of the studies. Five trials randomizing 1946 women (1766 analyzed) evaluated the effects of vaginal cleansing (all with povidone-iodine) on post-cesarean infectious morbidity. The risk of bias was generally low, with the quality of most of the studies being high. Vaginal preparation immediately before cesarean delivery significantly reduced the incidence of post-cesarean endometritis from 7.2% in control groups to 3.6% in vaginal cleansing groups (average risk ratio (RR) 0.39, 95% confidence interval (CI) 0.16 to 0.97, five trials, 1766 women). The risk reduction was particularly strong for women with ruptured membranes (1.4% in the vaginal cleansing group versus 15.4% in the control group; RR 0.13, 95% CI 0.02 to 0.66, two trials, 148 women). No other outcomes realized statistically significant differences between the vaginal cleansing and control groups. No adverse effects were reported with the povidone-iodine vaginal cleansing.The quality of the evidence using GRADE was low for post-cesarean endometritis

Application of the low-level laser therapy for the treatment of vaginitis

NASA Astrophysics Data System (ADS)

Passeniouk, A. N.; Mikhailov, V. A.

2000-06-01

Vaginitis is the most common female infectious disease. Females suffering from this disorder are annually increasing in number. There are a lot of modalities of treatment of vaginitis, but because of drug allergy and microbe's stability to drug the treatment of vaginitis is difficult. Our study compares the efficacy of laser-therapy with drug therapy in the treatment of non-specific vaginitis and vaginal candidiasis. Thirty women reci4eed the LLLT by local action with antiseptic liquid daily during ten days, 20 women received metronidazole and fluconozole and vaginal application of metronidazole. The results suggest that local laser-therapy is able to remove sights of vaginitis more efficiently and faster than drug therapy. Repair of normal vaginal microflora, which is the best indicator of recovery, was significantly at a faster rate in laser-therapy group. There were no report of adverse reaction with vaginal laser- therapy, whereas there were women on drug therapy who reported side effects. In conclusion, vaginal aser-therapy with antiseptic liquid is a suitable, effective, safe and chip alternative to drug therapy in the treatment of vaginitis.

Rapidly separating microneedles for transdermal drug delivery.

PubMed

Zhu, Dan Dan; Wang, Qi Lei; Liu, Xu Bo; Guo, Xin Dong

2016-09-01

The applications of polymer microneedles (MNs) into human skin emerged as an alternative of the conventional hypodermic needles. However, dissolving MNs require many minutes to be dissolved in the skin and typically have difficulty being fully inserted into the skin, which may lead to the low drug delivery efficiency. To address these issues, we introduce rapidly separating MNs that can rapidly deliver drugs into the skin in a minimally invasive way. For the rapidly separating MNs, drug loaded dissolving MNs are mounted on the top of solid MNs, which are made of biodegradable polylactic acid which eliminate the biohazardous waste. These MNs have sufficient mechanical strength to be inserted into the skin with the drug loaded tips fully embedded for subsequent dissolution. Compared with the traditional MNs, rapidly separating MNs achieve over 90% of drug delivery efficiency in 30s while the traditional MNs needs 2min to achieve the same efficiency. With the in vivo test in mice, the micro-holes caused by rapidly separating MNs can heal in 1h, indicating that the rapidly separating MNs are safe for future applications. These results indicate that the design of rapidly separating dissolvable MNs can offer a quick, high efficient, convenient, safe and potentially self-administered method of drug delivery. Polymer microneedles offer an attractive, painless and minimally invasive approach for transdermal drug delivery. However, dissolving microneedles require many minutes to be dissolved in the skin and typically have difficulty being fully inserted into the skin due to the skin deformation, which may lead to the low drug delivery efficiency. In this work we proposed rapidly separating microneedles which can deliver over 90% of drug into the skin in 30s. The in vitro and in vivo results indicate that the new design of these microneedles can offer a quick, high efficient, convenient and safe method for transdermal drug delivery. Copyright © 2016 Acta Materialia Inc

Engineered Polymers for Advanced Drug Delivery

PubMed Central

Kim, Sungwon; Kim, Jong-Ho; Jeon, Oju; Kwon, Ick Chan; Park, Kinam

2009-01-01

Engineered polymers have been utilized for developing advanced drug delivery systems. The development of such polymers has caused advances in polymer chemistry, which, in turn, has resulted in smart polymers that can respond to changes in environmental condition, such as temperature, pH, and biomolecules. The responses vary widely from swelling/deswelling to degradation. Drug-polymer conjugates and drug-containing nano/micro-particles have been used for drug targeting. Engineered polymers and polymeric systems have also been used in new areas, such as molecular imaging as well as in nanotechnology. This review examines the engineered polymers that have been used as traditional drug delivery and as more recent applications in nanotechnology. PMID:18977434

Inhaled Micro/Nanoparticulate Anticancer Drug Formulations: An Emerging Targeted Drug Delivery Strategy for Lung Cancers.

PubMed

Islam, Nazrul; Richard, Derek

2018-05-24

Local delivery of drug to the target organ via inhalation offers enormous benefits in the management of many diseases. Lung cancer is the most common of all cancers and it is the leading cause of death worldwide. Currently available treatment systems (intravenous or oral drug delivery) are not efficient in accumulating the delivered drug into the target tumor cells and are usually associated with various systemic and dose-related adverse effects. The pulmonary drug delivery technology would enable preferential accumulation of drug within the cancer cell and thus be superior to intravenous and oral delivery in reducing cancer cell proliferation and minimising the systemic adverse effects. Site-specific drug delivery via inhalation for the treatment of lung cancer is both feasible and efficient. The inhaled drug delivery system is non-invasive, produces high bioavailability at low dose and avoids first pass metabolism of the delivered drug. Various anticancer drugs including chemotherapeutics, proteins and genes have been investigated for inhalation in lung cancers with significant outcomes. Pulmonary delivery of drugs from dry powder inhaler (DPI) formulation is stable and has high patient compliance. Herein, we report the potential of pulmonary drug delivery from dry powder inhaler (DPI) formulations inhibiting lung cancer cell proliferation at very low dose with reduced unwanted adverse effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Maternal and neonatal outcomes of vaginal breech delivery for singleton term pregnancies in a carefully selected Cameroonian population: a cohort study

PubMed Central

Dohbit, Julius Sama; Foumane, Pascal; Mamoudou, Fadimatou; Temgoua, Mazou N; Tankeu, Ronni; Aletum, Veronica; Mboudou, Emile

2017-01-01

Background and objectives Vaginal breech delivery (VBD) is known to be associated with more perinatal and maternal complications. Very few studies on the subject have been carried out in poor-resource settings. The aim of this study was to determine maternal and neonatal outcomes in carefully selected cases of VBD for singleton term pregnancies in a tertiary centre in Cameroon. Design A retrospective cohort study. Setting A tertiary hospital in Yaounde, Cameroon. Participants Cases of VBD of newborns weighing 2500–3500 g were matched in a ratio of 1:4 to consecutive vaginal cephalic deliveries (VCDs) of newborns weighing 2500–3500 g over a 5-year period. Both groups were matched for maternal age and parity. We excluded cases of multiple gestations, footling breech, clinically inadequate maternal pelvis, preterm delivery, post-term pregnancies, fetal demise prior to the onset of labour, placenta praevia and fetal anomaly incompatible with vaginal delivery. Outcome measures Neonatal and maternal adverse outcomes of VBD observed till 6 weeks after delivery analysed using Bonferroni correction. Results Fifty-three (53) VBDs were matched against 212 VCD. Unlike women who had VCD, those who underwent VBD were more likely to have prolonged labour (OR 8.05; 95% CI 3.00 to 11.47; P<0.001), and their newborns were more likely to suffer from birth asphyxia (OR 10.24; 95% CI 4.92 to 21.31; P<0.001). Conclusion The study infers a strong association between VBD of singleton term pregnancies and maternofetal morbidity when specific protocols are applied. This, however, failed to translate into higher differences in perinatal mortality. This finding does not discount the role of VBD in low-income countries, but we emphasise the need for specific precautions like close monitoring of labour and adequate anticipation for neonatal resuscitation in order to reduce these complications. PMID:29170287

Infrared free electron laser enhanced transdermal drug delivery

NASA Astrophysics Data System (ADS)

Awazu, Kunio; Uchizono, Takeyuki; Suzuki, Sachiko; Yoshikawa, Kazushi

2005-08-01

It is necessary to control enhancement of transdermal drug delivery with non-invasive. The present study was investigated to assess the effectivity of enhancing the drug delivery by irradiating 6-μm region mid infrared free electron laser (MIR-FEL). The enhancement of transdermal drug (lidocaine) delivery of the samples (hairless mouse skin) irradiated with lasers was examined for flux (μg/cm2/h) and total penetration amount (μg/cm2) of lidocaine by High performance Liquid Chromatography (HPLC). The flux and total amount penatration date was enhanced 200-300 fold faster than the control date by the laser irradiation. FEL irradiating had the stratum corneum, and had the less thermal damage in epidermis. The effect of 6-μm region MIR-FEL has the enhancement of transdermal drug delivery without removing the stratum corneum because it has the less thermal damage. It leads to enhancement drug delivery system with non-invasive laser treatment.

Novel Strategies for Anterior Segment Ocular Drug Delivery

PubMed Central

Cholkar, Kishore; Patel, Sulabh P.; Vadlapudi, Aswani Dutt

2013-01-01

Abstract Research advancements in pharmaceutical sciences have led to the development of new strategies in drug delivery to anterior segment. Designing a new delivery system that can efficiently target the diseased anterior ocular tissue, generate high drug levels, and maintain prolonged and effective concentrations with no or minimal side effects is the major focus of current research. Drug delivery by traditional method of administration via topical dosing is impeded by ocular static and dynamic barriers. Various products have been introduced into the market that prolong drug retention in the precorneal pocket and to improve bioavailability. However, there is a need of a delivery system that can provide controlled release to treat chronic ocular diseases with a reduced dosing frequency without causing any visual disturbances. This review provides an overview of anterior ocular barriers along with strategies to overcome these ocular barriers and deliver therapeutic agents to the affected anterior ocular tissue with a special emphasis on nanotechnology-based drug delivery approaches. PMID:23215539

Thiolated polymers as mucoadhesive drug delivery systems.

PubMed

Duggan, Sarah; Cummins, Wayne; O' Donovan, Orla; Hughes, Helen; Owens, Eleanor

2017-03-30

Mucoadhesion is the process of binding a material to the mucosal layer of the body. Utilising both natural and synthetic polymers, mucoadhesive drug delivery is a method of controlled drug release which allows for intimate contact between the polymer and a target tissue. It has the potential to increase bioavailability, decrease potential side effects and offer protection to more sensitive drugs such as proteins and peptide based drugs. The thiolation of polymers has, in the last number of years, come to the fore of mucoadhesive drug delivery, markedly improving mucoadhesion due to the introduction of free thiol groups onto the polymer backbone while also offering a more cohesive polymeric matrix for the slower and more controlled release of drug. This review explores the concept of mucoadhesion and the recent advances in both the polymers and the methods of thiolation used in the synthesis of mucoadhesive drug delivery devices. Copyright © 2017 Elsevier B.V. All rights reserved.

Role of Nanodiamonds in Drug Delivery and Stem Cell Therapy.

PubMed

Ansari, Shakeel Ahmed; Satar, Rukhsana; Jafri, Mohammad Alam; Rasool, Mahmood; Ahmad, Waseem; Kashif Zaidi, Syed

2016-09-01

The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Nanodiamonds (NDs) have contributed significantly in the development of highly efficient and successful drug delivery systems, and in stem cell therapy. Drug delivery through NDs is an intricate and complex process that deserves special attention to unravel underlying molecular mechanisms in order to overcome certain bottlenecks associated with it. It has already been established that NDs based drug delivery systems have excellent biocompatibility, nontoxicity, photostability and facile surface functionalization properties. There is mounting evidence that suggests that such conjugated delivery systems well retain the properties of nanoparticles like small size, large surface area to volume ratio that provide greater biocatalytic activity to the attached drug in terms of selectivity, loading and stability. NDs based drug delivery systems may form the basis for the development of effective novel drug delivery vehicles with salient features that may facilitate their utility in fluorescence imaging, target specificity and sustainedrelease.

Preformulation and Vaginal Film Formulation Development of Microbicide Drug Candidate CSIC for HIV prevention.

PubMed

Gong, Tiantian; Zhang, Wei; Parniak, Michael A; Graebing, Phillip W; Moncla, Bernard; Gupta, Phalguni; Empey, Kerry M; Rohan, Lisa C

2017-06-01

5-chloro-3-[phenylsulfonyl] indole-2-carboxamide (CSIC) is a highly potent non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1 which has been shown to have a more desirable resistance profile than other NNRTIs in development as HIV prevention strategies. This work involves generation of preformulation data for CSIC and systematic development of a cosolvent system to effectively solubilize this hydrophobic drug candidate. This system was then applied to produce a polymeric thin film solid dosage form for vaginal administration of CSIC for use in prevention of sexual acquisition of HIV. Extensive preformulation, formulation development, and film characterization studies were conducted. An HPLC method was developed for CSIC quantification. Preformulation tests included solubility, crystal properties, stability, and drug-excipient compatibility. Cytotoxicity was evaluated using both human epithelial and mouse macrophage cell lines. Ternary phase diagram methodology was used to identify a cosolvent system for CSIC solubility enhancement. Following preformulation evaluation, a CSIC film formulation was developed and manufactured using solvent casting technique. The developed film product was assessed for physicochemical properties, anti-HIV bioactivity, and Lactobacillus biocompatibility during 12-month stability testing period. Preformulation studies showed CSIC to be very stable. Due to its hydrophobicity, a cosolvent system consisting of polyethylene glycol 400, propylene glycol, and glycerin (5:2:1, w/w/w ) was developed, which provided a uniform dispersion of CSIC in the film formulation. The final film product met target specifications established for vaginal microbicide application. The hydrophobic drug candidate CSIC was successfully formulated with high loading capacity in a vaginal film by means of a cosolvent system. The developed cosolvent strategy is applicable for incorporation of other hydrophobic drug candidates in the film platform.

Bupivacaine compared with etidocaine for vaginal delivery.

PubMed

Moore, D C; Bridenbaugh, P O; Bridenbaugh, L D; Thompson, G E; Balfour, R I; Lysons, D F

1975-01-01

A comparison of 0.5 percent etidocaine with 0.25 and 0.5 percent bupivacaine, using continuous (intermittent) caudal block in 60 vaginal deliveries, showed the latter two solutions to be the agents of choice. All solutions contained a final concentration of 1:2000,000 epihephrine. In 40 parturients given either 0.25 or 0.5 percent bupivacaine, all had pain relief after the initial dose, while 5 of 20 given etidocaine required a refill dose within 30 to 50 minutes for complete pain relief. The duration of action of the initial dose with both concentrations of bupivacaine was longer than that of etidocaine. The degree of motor blockade with 0.5 percent etidocaine was greater than with 0.5 percent bupivacaine, and with 0.5 percent concentrations of either etidocaine or bupivacaine was greater than with 0.25 percent bupivacaine. The duration of motor blockade of 0.5 percent etidocaine and bupivacaine was comparable. The duration of motor blockade of the 0.25 percent concentration of bupivacaine was shorter than with the 0.5 percent concentration of both etidocaine and bupivacaine; and with both bupivacaine concentrations the duration of sensory anesthesia in the extremities was longer than motor blockade; with etidocaine, the opposite occurred.

Effect of early oral clindamycin on late miscarriage and preterm delivery in asymptomatic women with abnormal vaginal flora and bacterial vaginosis: a randomised controlled trial.

PubMed

Ugwumadu, Austin; Manyonda, Isaac; Reid, Fiona; Hay, Phillip

2003-03-22

Abnormal vaginal flora and bacterial vaginosis are associated with amplified risks of late miscarriage and spontaneous preterm delivery. We aimed to establish whether antibiotic treatment early in the second trimester might reduce these risks in a general obstetric population. We screened 6120 pregnant women attending hospital for their first antenatal visit--who were at 12-22 weeks' gestation (mean 15.6 weeks)--for bacterial vaginosis or abnormal vaginal flora. We used gram-stained slides of vaginal smears to diagnose abnormal vaginal flora or bacterial vaginosis, in accordance with Nugent's criteria. We randomly allocated 494 women with one of these signs to receive either clindamycin 300 mg or placebo orally twice daily for 5 days. Primary endpoints were spontaneous preterm delivery (birth > or =24 but <37 weeks) and late miscarriage (pregnancy loss > or =13 but <24 weeks). Analysis was intention to treat. Nine women were lost to follow-up or had elective termination. Thus, we analysed 485 women with complete outcome data. Women receiving clindamycin had significantly fewer miscarriages or preterm deliveries (13/244) than did those in the placebo group (38/241; percentage difference 10.4%, 95% CI 5.0-15.8, p=0.0003). Clindamycin also reduced adverse outcomes across the range of abnormal Nugent scores, with maximum effect in women with the highest Nugent score of 10. Treatment of asymptomatic abnormal vaginal flora and bacterial vaginosis with oral clindamycin early in the second trimester significantly reduces the rate of late miscarriage and spontaneous preterm birth in a general obstetric population.

Simulation to Improve Trainee Knowledge and Comfort About Twin Vaginal Birth.

PubMed

Easter, Sarah Rae; Gardner, Roxane; Barrett, Jon; Robinson, Julian N; Carusi, Daniela

2016-10-01

To describe a simulation-based curriculum on twin vaginal delivery and evaluate its effects on trainee knowledge and comfort about twin vaginal birth. Trainees participated in a three-part simulation consisting of a patient counseling session, a twin delivery scenario, and a breech extraction skills station. Consenting trainees completed a 21-item presimulation survey and a 22-item postsimulation survey assessing knowledge, experience, attitudes, and comfort surrounding twin vaginal birth. Presimulation and postsimulation results were compared using univariate analysis. Our primary outcomes were change in knowledge and comfort before and after the simulation. Twenty-four obstetrics and gynecology residents consented to participation with 18 postsimulation surveys available for comparison (75%). Trainees estimated their participation in 445 twin deliveries (median 19, range 0-52) with only 20.4% of these as vaginal births. Participants reported a need for more didactic or simulated training on this topic (64% and 88%, respectively). Knowledge about twin delivery improved after the simulation (33.3% compared with 58.3% questions correct, P<.01). Before training, 33.3% of participants reported they would strongly counsel a patient to attempt vaginal birth instead of elective cesarean delivery for twins compared with 50% after training (P=.52). Personal comfort with performing a breech extraction of a nonvertex second twin improved from 5.5% to 66.7% after the simulation (P<.01). Resident exposure to twin vaginal birth is infrequent and variable with a demonstrable need for more training. Our contemporary obstetric climate is prioritizing vaginal birth despite less frequent operative obstetric interventions. We describe a reproducible twin delivery simulation associated with a favorable effect on resident knowledge and comfort levels.

Micro-scale Devices for Transdermal Drug Delivery

PubMed Central

Arora, Anubhav; Prausnitz, Mark; Mitragotri, Samir

2009-01-01

Skin makes an excellent site for drug and vaccine delivery due to easy accessibility, immuno-surveillance functions, avoidance of macromolecular degradation in the gastrointestinal tract and possibility of self-administration. However, macromolecular drug delivery across the skin is primarily accomplished using hypodermic needles, which have several disadvantages including accidental needle-sticks, pain and needle phobia. These limitations have led to extensive research and development of alternative methods for drug and vaccine delivery across the skin. This review focuses on the recent trends and developments in this field of micro-scale devices for transdermal macromolecular delivery. These include liquid jet injectors, powder injectors, microneedles and thermal microablation. The historical perspective, mechanisms of action, important design parameters, applications and challenges are discussed for each method. PMID:18805472

Facilitation of transscleral drug delivery by drug loaded magnetic polymeric particles.

PubMed

Mousavikhamene, Zeynab; Abdekhodaie, Mohammad J; Ahmadieh, Hamid

2017-10-01

A unique method was used to facilitate ocular drug delivery from periocular route by drug loaded magnetic sensitive particles. Injection of particles in periocular space along the eye axis followed by application of magnetic field in front of the eye would trigger the magnetic polymeric particles to move along the direction of magnetic force and reside against the outer surface of the sclera. This technique prevents removal of drug in the periocular space, observed in conventional transscleral drug delivery systems and hence higher amount of drug can enter the eye in a longer period of time. The experiments were performed by fresh human sclera and an experimental setup. Experimental setup was designed by side by side diffusion cell and hydrodynamic and thermal simulation of the posterior segment of the eye were applied. Magnetic polymeric particles were synthesized by alginate as a model polymer, iron oxide nanoparticles as a magnetic agent and diclofenac sodium as a model drug and characterized by SEM, TEM, DLS and FT-IR techniques. According to the SEM images, the size range of particles is around 60 to 800nm. The results revealed that the cumulative drug transfer from magnetic sensitive particles across the sclera improves by 70% in the presence of magnetic field. The results of this research show promising method of drug delivery to use magnetic properties to facilitate drug delivery to the back of the eye. Copyright © 2017. Published by Elsevier B.V.

[Smart drug delivery systems based on nanoscale ZnO].

PubMed

Huang, Xiao; Chen, Chun; Yi, Caixia; Zheng, Xi

2018-04-01

In view of the excellent biocompatibility as well as the low cost, nanoscale ZnO shows great potential for drug delivery application. Moreover, The charming character enable nanoscale ZnO some excellent features (e.g. dissolution in acid, ultrasonic permeability, microwave absorbing, hydrophobic/hydrophilic transition). All of that make nanoscale ZnO reasonable choices for smart drug delivery. In the recent decade, more and more studies have focused on controlling the drug release behavior via smart drug delivery systems based on nanoscale ZnO responsive to some certain stimuli. Herein, we review the recent exciting progress on the pH-responsive, ultrasound-responsive, microwave-responsive and UV-responsive nanoscale ZnO-based drug delivery systems. A brief introduction of the drug controlled release behavior and its effect of the drug delivery systems is presented. The biocompatibility of nanoscale ZnO is also discussed. Moreover, its development prospect is looked forward.

[Methods of pushing at vaginal delivery and pelvi-perineal consequences. Review].

PubMed

Ratier, N; Balenbois, E; Letouzey, V; Marès, P; de Tayrac, R

2015-03-01

The main objective of that review was to evaluate the pelvi-perineal consequences of the different methods of pushing at vaginal delivery. A review on PubMed, the Cochrane Library and EM-Premium was performed from 1984 to 2014. Among 29 manuscripts analysed, only nine randomised controlled trials (including one meta-analysis of three trials) comparing Valsalva and spontaneous pushing were selected. A 10 th study, secondary analysis of a randomized controlled trial comparing different methods of perineal protection (warm compresses, massage and manual protection), was also selected. Two trials have shown that spontaneous pushing reduces the risk of perineal tears, but studies were heterogeneous and discordant results do not allowed definitive conclusions. Results on the duration of the second stage of labour are conflicting. The method of pushing does not seem to affect the rate of episiotomy, instrumental delivery and cesarean section. Maternal satisfaction seems to be better after spontaneous pushing. It seems that there is no negative effect of spontaneous pushing on neonate well-being, and one study has shown a significant improvement of prenatal fetal parameters during the expulsive phase. According to current knowledge, both techniques of pushing during the expulsive phase at delivery seem comparable in terms of duration, risk of perineal tears and neonatal outcome. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Ultrasound mediated nanoparticle drug delivery

NASA Astrophysics Data System (ADS)

Mullin, Lee B.

Ultrasound is not only a powerful diagnostic tool, but also a promising therapeutic technology that can be used to improve localized drug delivery. Microbubble contrast agents are micron sized encapsulated gas filled bubbles that are administered intravenously. Originally developed to enhance ultrasound images, microbubbles are highly echogenic due to the gas core that provides a detectable impedance difference from the surrounding medium. The core also allows for controlled response of the microbubbles to ultrasound pulses. Microbubbles can be pushed using acoustic radiation force and ruptured using high pressures. Destruction of microbubbles can increase permeability at the cellular and vascular level, which can be advantageous for drug delivery. Advances in drug delivery methods have been seen with the introduction of nanoparticles, nanometer sized objects often carrying a drug payload. In chemotherapy, nanoparticles can deliver drugs to tumors while limiting systemic exposure due to abnormalities in tumor vasculature such large gaps between endothelial cells that allow nanoparticles to enter into the interstitial space; this is referred to as the enhanced permeability and retention (EPR) effect. However, this effect may be overestimated in many tumors. Additionally, only a small percentage of the injected dose accumulates in the tumor, which most the nanoparticles accumulating in the liver and spleen. It is hypothesized that combining the acoustic activity of an ultrasound contrast agent with the high payload and extravasation ability of a nanoparticle, localized delivery to the tumor with reduced systemic toxicity can be achieved. This method can be accomplished by either loading nanoparticles onto the shell of the microbubble or through a coadministration method of both nanoparticles and microbubbles. The work presented in this dissertation utilizes novel and commercial nanoparticle formulations, combined with microbubbles and a variety of ultrasound systems

The impact of manual rotation of the occiput posterior position on spontaneous vaginal delivery rate: study protocol for a randomized clinical trial (RMOS).

PubMed

Verhaeghe, C; Parot-Schinkel, E; Bouet, P E; Madzou, S; Biquard, F; Gillard, P; Descamps, P; Legendre, G