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Experimental Eye Research Nov 2020Bio-engineering technologies are currently used to produce biomimetic artificial corneas that should present structural, chemical, optical, and biomechanical properties... (Review)
Review
Bio-engineering technologies are currently used to produce biomimetic artificial corneas that should present structural, chemical, optical, and biomechanical properties close to the native tissue. These properties are mainly supported by the corneal stroma which accounts for 90% of corneal thickness and is mainly made of collagen type I. The stromal collagen fibrils are arranged in lamellae that have a plywood-like organization. The fibril diameter is between 25 and 35 nm and the interfibrillar space about 57 nm. The number of lamellae in the central stroma is estimated to be 300. In the anterior part, their size is 10-40 μm. They appear to be larger in the posterior part of the stroma with a size of 60-120 μm. Their thicknesses also vary from 0.2 to 2.5 μm. During development, the acellular corneal stroma, which features a complex pattern of organization, serves as a scaffold for mesenchymal cells that invade and further produce the cellular stroma. Several pathways including Bmp4, Wnt/β-catenin, Notch, retinoic acid, and TGF-β, in addition to EFTFs including the mastering gene Pax-6, are involved in corneal development. Besides, retinoic acid and TGF- β seem to have a crucial role in the neural crest cell migration in the stroma. Several technologies can be used to produce artificial stroma. Taking advantage of the liquid-crystal properties of acid-soluble collagen, it is possible to produce transparent stroma-like matrices with native-like collagen I fibrils and plywood-like organization, where epithelial cells can adhere and proliferate. Other approaches include the use of recombinant collagen, cross-linkers, vitrification, plastically compressed collagen or magnetically aligned collagen, providing interesting optical and mechanical properties. These technologies can be classified according to collagen type and origin, presence of telopeptides and native-like fibrils, structure, and transparency. Collagen matrices feature transparency >80% for the appropriate 500-μm thickness. Non-collagenous matrices made of biopolymers including gelatin, silk, or fish scale have been developed which feature interesting properties but are less biomimetic. These bioengineered matrices still need to be colonized by stromal cells to fully reproduce the native stroma.
Topics: Animals; Bioengineering; Collagen; Corneal Stroma; Drug Implants; Humans; Mesenchymal Stem Cells; Recombinant Proteins
PubMed: 32971095
DOI: 10.1016/j.exer.2020.108256 -
Contraception Sep 2016This study aims to systematically review evidence published on the safety of Sino-implant (II) [SI (II)] among women with medical conditions or characteristics... (Review)
Review
OBJECTIVES
This study aims to systematically review evidence published on the safety of Sino-implant (II) [SI (II)] among women with medical conditions or characteristics identified by the World Health Organization for eligibility for contraceptive use.
STUDY DESIGN
We searched PubMed, WEIPU, CNKI and Wanfang to identify all relevant evidence published in peer-reviewed journals from 1991 through 2014 regarding the safety of SI (II). We considered studies among women with medical conditions or other characteristics, such as age and parity, as direct evidence and studies among healthy women or a general population of women as indirect evidence.
RESULTS
We identified 108 articles of which 9 met our inclusion criteria. Among women with medical conditions, no evidence was identified for the outcomes of interest, including serious adverse events or outcomes related to medical conditions. Among healthy women, evidence regarding efficacy of SI (II) for women weighing ≥70 kg was conflicting; one study showed an increased pregnancy rate and another showed no relationship. Women with menorrhagia did not experience worsened symptoms and may benefit from SI (II) use. Healthy women using SI (II) were no more likely than users of other methods to gain weight, develop elevated blood pressure, have abnormal liver or bone density tests or develop ovarian cysts or uterine myomas.
CONCLUSIONS
Evidence among healthy women suggests SI (II) is safe and had health outcomes similar to those of other levonorgestrel implants. Studies were limited and conflicting regarding efficacy for women ≥70 kg. All included studies were conducted in China, limiting generalizability.
Topics: Bone Density; China; Contraception Behavior; Contraceptive Agents, Female; Drug Implants; Female; Humans; Leiomyoma; Levonorgestrel; Ovarian Cysts; Patient Satisfaction; Randomized Controlled Trials as Topic; Weight Gain
PubMed: 27217053
DOI: 10.1016/j.contraception.2016.05.004 -
Journal of Women's Health (2002) Dec 2019Long-acting reversible contraception (LARC) is highly effective at preventing pregnancy. However, in sub-Saharan Africa, LARC education for clients is relatively...
Long-acting reversible contraception (LARC) is highly effective at preventing pregnancy. However, in sub-Saharan Africa, LARC education for clients is relatively limited and providers are often not skilled in their insertion. Before 2009, only 1% of family planning clients in Rwanda received an LARC. We trained Rwandan government clinic nurses to promote, insert, and remove copper intrauterine devices (IUDs) and hormonal implants. Training started in two large urban clinics, and those nurses trained three successive waves of clinic nurses. Initial LARC promotions were clinic based, but in 2015 included community-based promotions in eight clinics. We compare IUD and implant insertions by year and clinic and discuss implementation successes/obstacles. From 2009 to 2016, 222 nurses from 21 government clinics were LARC trained. The nurses performed 36,588 LARC insertions (19% IUD, 81% implant). LARC insertions increased over time, peaking at 8,897 in 2013. However, in 2014, the number dropped to 4,018 after closure of one large clinic, funding discontinuation, and supply stock-outs. With new funding in 2015, insertions increased reaching 8,218 in 2016. Catholic and non-Catholic and rural and urban clinics performed similarly, whereas clinics affiliated with community-based promotions performed better ( > 0.05). Between 2012 and 2014, 13% of family planning initiators chose the implant and 4% the IUD. LARC supply-demand services increased the proportion of family planning initiators choosing LARC to 17%. Challenges included inconsistent funding, irregular supplies, and staff turnover. Rural and Catholic clinics performed as well as urban and non-Catholic clinics. Concerted efforts to improve IUD uptake are needed.
Topics: Contraceptive Agents, Hormonal; Drug Implants; Family Planning Services; Female; Humans; Intrauterine Devices, Copper; Long-Acting Reversible Contraception; Nurses, Community Health; Rwanda
PubMed: 31274397
DOI: 10.1089/jwh.2018.7423 -
Journal of Controlled Release :... Nov 2023Different types of ibuprofen-loaded, poly (D,L lactic-co-glycolic acid) (PLGA)-based implants were prepared by 3D printing (Droplet Deposition Modeling). The theoretical...
Different types of ibuprofen-loaded, poly (D,L lactic-co-glycolic acid) (PLGA)-based implants were prepared by 3D printing (Droplet Deposition Modeling). The theoretical filling density of the mesh-shaped implants was varied from 10 to 100%. Drug release was measured in agarose gels and in well agitated phosphate buffer pH 7.4. The key properties of the implants (and dynamic changes thereof upon exposure to the release media) were monitored using gravimetric measurements, optical microscopy, Differential Scanning Calorimetry, Gel Permeation Chromatography, and Scanning Electron Microscopy. Interestingly, drug release was similar for implants with 10 and 30% filling density, irrespective of the experimental set-up. In contrast, implants with 100% filling density showed slower release kinetics, and the shape of the release curve was altered in agarose gels. These observations could be explained by the existence (or absence) of a continuous aqueous phase between the polymeric filaments and the "orchestrating role" of substantial system swelling for the control of drug release. At lower filling densities, it is sufficient for the drug to be released from a single filament. In contrast, at high filling densities, the ensemble of filaments acts as a much larger (more or less homogeneous) polymeric matrix, and the average diffusion pathway to be overcome by the drug is much longer. Agarose gel (mimicking living tissue) hinders substantial PLGA swelling and delays the onset of the final rapid drug release phase. This improved mechanistic understanding of the control of drug release from PLGA-based 3D printed implants can help to facilitate the optimization of this type of advanced drug delivery systems.
Topics: Polylactic Acid-Polyglycolic Acid Copolymer; Drug Liberation; Polyglycolic Acid; Sepharose; Lactic Acid; Gels; Printing, Three-Dimensional; Drug Implants
PubMed: 37714435
DOI: 10.1016/j.jconrel.2023.09.020 -
Cleveland Clinic Journal of Medicine Nov 2015Long-acting reversible contraceptives (LARCs) are safe for use in adolescents and do not rely on compliance or adherence for effectiveness. Continuation rates are higher... (Review)
Review
Long-acting reversible contraceptives (LARCs) are safe for use in adolescents and do not rely on compliance or adherence for effectiveness. Continuation rates are higher and pregnancy rates are lower for adolescent users of LARCs compared with short-acting methods such as oral contraceptives. Similarly, repeat pregnancy rates are lower when LARCs are used compared with other forms of contraception. Myths and misconceptions about LARCs and other contraceptives remain a barrier to their use. Health care providers are in a unique position to provide confidential care to adolescents, and should provide education to them about the various contraceptive options, especially LARCs.
Topics: Adolescent; Contraceptive Agents, Female; Desogestrel; Drug Implants; Female; Humans; Intrauterine Devices; Pregnancy; Pregnancy in Adolescence
PubMed: 26555813
DOI: 10.3949/ccjm.82.s1.02 -
Drug Design, Development and Therapy 2015The purpose of this meta-analysis was to assess the efficacy and safety of intravitreal corticosteroid implants for macular edema. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The purpose of this meta-analysis was to assess the efficacy and safety of intravitreal corticosteroid implants for macular edema.
METHODS
A total of 3,586 patients from previously reported randomized controlled trials were included. The meta-analysis was performed using RevMan 5.2. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, employing random-effects or fixed-effects models according to between-study heterogeneity. The main outcome measures were the ORs for effects and safety of intravitreal corticosteroid implants.
RESULTS
Four eligible studies were included. Compared with the sham group, the ORs for ≥15 letter improvement of visual acuity in the high-dose and low-dose groups were 1.89 (95% CI 1.33-2.69, P=0.0004) and 1.62 (95% CI 1.10-2.41, P=0.02), respectively. The weight mean differences in central retinal thickness increases were -75.46 (95% CI -90.29, -60.63, P<0.0001) and -46.47 (95% CI -92.08, -0.86, P=0.05), respectively. However, the ORs for increased intraocular pressure in both intervention groups were higher than in the sham group, and were 11.50 (95% CI 7.24-18.28, P<0.00001) and 10.30 (95% CI 6.49-16.36, P<0.00001), respectively. The incidence of cataract was 7.25 (95% CI 5.68-9.25, P<0.00001) and 3.56 (95% CI 1.28-9.96, P=0.02) in the two intervention groups, respectively. There was no significant difference between the intervention groups except for the incidence of cataract in which the OR was 1.59 (95% CI 1.28-1.97, P<0.001).
CONCLUSION
Intravitreal corticosteroid implants are effective in treating macular edema. However, the efficacy is not related to corticosteroid dose.
Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Delayed-Action Preparations; Drug Implants; Humans; Macular Edema; Randomized Controlled Trials as Topic
PubMed: 26005329
DOI: 10.2147/DDDT.S82929 -
International Journal of Gynaecology... Jan 2019Extending contraceptive implant duration of use increases accessibility by maximizing the lifetime of devices.
BACKGROUND
Extending contraceptive implant duration of use increases accessibility by maximizing the lifetime of devices.
OBJECTIVES
To review the contraceptive efficacy during extended use of progestin implants.
SEARCH STRATEGY
PubMed and EMBASE were searched for articles in any language, 1996-2017, utilizing terms for devices and contraceptive efficacy.
SELECTION CRITERIA
Randomized clinical trials (RCTs), cohort studies, and case-control studies were included; abstracts, posters, and presentations were excluded. Studies evaluating Norplant and implants currently in pre-marketing trials were excluded.
DATA COLLECTION AND ANALYSIS
Titles and abstracts of articles were reviewed; those that met inclusion and exclusion criteria underwent full text review and data abstraction.
MAIN RESULTS
The search identified 2951 articles; six met inclusion and exclusion criteria. Five studies evaluated the etonogestrel implant (Implanon), and one the levonorgestrel implant (Jadelle). One RCT randomized to method, not duration; the remaining studies were prospective cohort studies. Three studies analyzed efficacy among women beyond currently approved duration separately. All studies were of poor to fair quality by United States Preventative Services Task Force (USPTF) grading. Limitations include lack of generalizability and control of important confounders.
CONCLUSION
These studies provide limited data for extended duration of contraceptive implants.
Topics: Adult; Case-Control Studies; Contraceptive Agents, Female; Desogestrel; Drug Implants; Female; Humans; Levonorgestrel; Progestins; Prospective Studies; Randomized Controlled Trials as Topic; Time Factors
PubMed: 30343503
DOI: 10.1002/ijgo.12696 -
Obstetrics and Gynecology Apr 2022To evaluate topiramate and etonogestrel pharmacokinetic interactions in contraceptive implant users.
OBJECTIVE
To evaluate topiramate and etonogestrel pharmacokinetic interactions in contraceptive implant users.
METHODS
We conducted a prospective, noninferiority study with healthy women using etonogestrel implants continuously for 12-36 months. We measured baseline serum etonogestrel concentrations and then began a 6-week titrated topiramate regimen to standard migraine (100 mg/day) and epilepsy (400 mg/day) dosages. We repeated serum etonogestrel concentrations at 3 weeks (100 mg/day), 4 weeks (200 mg/day), and 6 weeks (400 mg/day) of topiramate therapy. We measured etonogestrel using a validated liquid chromatography-tandem, mass-spectrometry assay and tested for noninferiority (less than 30% decrease) in serum etonogestrel concentrations from baseline.
RESULTS
We enrolled 48 total participants; 32 completed 3 weeks, 31 completed 4 weeks, and 27 completed all follow-up visits. Participants' median age was 25.3 years (range 18.3-37.2), median body mass index (BMI) was 25.5 kg/m2 (range 18.7-42.2), and median duration of implant use was 24 months (range 12-36). Median etonogestrel concentrations were 142 pg/mL (range 76.2-771) at baseline, 126 pg/mL (range 72.4-585) at 3 weeks, 119 pg/mL (range 65.6-542) at 4 weeks, and 105 pg/mL (46.2-859) at 6 weeks. The 95% CIs for mean percent change in serum etonogestrel concentrations from baseline were [-37.3%+16.9%], [-45.4%+5.2%], and [-66.8%+24.8%] at 3 weeks, 4 weeks, and 6 weeks, respectively. Excluding one participant who had a serum etonogestrel concentration less than 90 pg/mL at baseline, 30.8% of participants (8/26, 95% CI 14.3-51.8%) had a serum etonogestrel concentration less than 90 pg/mL at 6 weeks.
CONCLUSION
Though only a mild enzyme-inducing antiepileptic drug, concomitant topiramate use led to inferior serum etonogestrel concentrations among implant users, with a significant proportion reaching etonogestrel concentrations below the threshold for ovulatory suppression when taking antiepileptic dosages of topiramate.
FUNDING SOURCE
This study was primarily funded through an Investigator-Initiated Study grant from Merck Sharp & Dohme Corp [MISP#57073]. This work was also supported by NIH/NCATS CTSA Grant Number UL1 TR001082 and NICHD K12 Women's Reproductive Health Research Scholar Program (grant number 5K12HD001271-18).
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, NCT03335163.
Topics: Adolescent; Adult; Contraceptive Agents, Female; Desogestrel; Drug Implants; Female; Humans; Prospective Studies; Topiramate; Young Adult
PubMed: 35594123
DOI: 10.1097/AOG.0000000000004697 -
Graefe's Archive For Clinical and... Jul 2016To review published data pertaining to the clinical experience with a dexamethasone intravitreal implant (Ozurdex®) with a view to establishing a clinically based... (Review)
Review
PURPOSE
To review published data pertaining to the clinical experience with a dexamethasone intravitreal implant (Ozurdex®) with a view to establishing a clinically based therapeutic regime.
METHODS
A PubMed search using the MeSH terms "retinal vein occlusion" and either "pathophysiology" or "dexamethasone intravitreal implant" was undertaken for manuscripts published until August 2015. The analysis included studies involving minimally 15 patients under a prospective design or 30 under a retrospective design, a minimal follow up of 6 months, and at least 2 intravitreal Ozurdex® injections per eye.
RESULTS
In the vast majority of eyes, satisfactory outcomes were achieved with retreatment intervals of between 3 and 5 months. Initial evidence indicates a similar efficacy compared to anti-VEGF therapies as a first-line treatment. Safety concerns associated with the long-term and repeated use of Ozurdex® are not borne out by clinical findings: its implantation is not associated with a sustained increase in intraocular pressure (IOP) over time or with the number of applications.
CONCLUSION
Compared with anti-VEGF therapies, the burden of retreatment is reduced. In patients with chronic macular edema not responsive to repetitive anti-VEGF therapies, the outcome after dexamethasone implant treatment is encouraging. However, these results are achieved at the expense of side effects typically associated with steroids: in up to 20 % of the Ozurdex®-treated patients, an elevation in IOP, which could be medically controlled in the majority of cases, and cataract formation or progression was observed.
Topics: Dexamethasone; Drug Implants; Glucocorticoids; Humans; Intravitreal Injections; Retinal Vein Occlusion; Tomography, Optical Coherence; Treatment Outcome; Visual Acuity
PubMed: 27178087
DOI: 10.1007/s00417-016-3350-x -
European Journal of Pharmaceutics and... Feb 2021In the field of drug delivery, the most commonly used treatments have traditionally been systemically delivered using oral or intravenous administration. The problems... (Review)
Review
In the field of drug delivery, the most commonly used treatments have traditionally been systemically delivered using oral or intravenous administration. The problems associated with this type of delivery is that the drug concentration is controlled by first pass metabolism, and therefore may not always remain within the therapeutic window. Implantable drug delivery systems (IDDSs) are an excellent alternative to traditional delivery because they offer the ability to precisely control the drug release, deliver drugs locally to the target tissue, and avoid the toxic side effects often experienced with systemic administration. Since the creation of the first FDA-approved IDDS in 1990, there has been a surge in research devoted to fabricating and testing novel IDDS formulations. The versatility of these systems is evident when looking at the various biomedical applications that utilize IDDSs. This review provides an overview of the history of IDDSs, with examples of the different types of IDDS formulations, as well as looking at current and future biomedical applications for such systems. Though there are still obstacles that need to be overcome, ever-emerging new technologies are making the manufacturing of IDDSs a rewarding therapeutic endeavor with potential for further improvements.
Topics: Delayed-Action Preparations; Drug Approval; Drug Compounding; Drug Implants; Drug-Eluting Stents; History, 20th Century; History, 21st Century; Humans; United States; United States Food and Drug Administration
PubMed: 33338604
DOI: 10.1016/j.ejpb.2020.12.005