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Current Diabetes Reports Nov 2019The aim of this review is to summarize the development of the photoactivated depot (PAD) approach for the minimally invasive and continuously variable delivery of... (Review)
Review
PURPOSE OF REVIEW
The aim of this review is to summarize the development of the photoactivated depot (PAD) approach for the minimally invasive and continuously variable delivery of insulin.
RECENT FINDINGS
Using an insulin PAD, we have demonstrated that we can release native, bioactive insulin into diabetic animals in response to light signals from a small external LED light source. We have further shown that this released insulin retains bioactivity and reduces blood glucose. In addition, we have designed and constructed second generation materials that have high insulin densities, with the potential for multiple day delivery. The PAD approach for insulin therapy holds promise for addressing the pressing need for continuously variable delivery methods that do not rely on pumps, and their myriad associated problems.
Topics: Animals; Blood Glucose; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Drug Implants; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Light; Photosensitizing Agents
PubMed: 31696345
DOI: 10.1007/s11892-019-1233-3 -
Drug Delivery Dec 2022The traditional systemic chemotherapy through intravenous infusion of doxorubicin (DOX) has many side effects. The aim of this study was to develop a PLGA-based...
The traditional systemic chemotherapy through intravenous infusion of doxorubicin (DOX) has many side effects. The aim of this study was to develop a PLGA-based DOX-loaded implant and to evaluate the efficacy and drug metabolism distribution of the implant in intratumoral chemotherapy for osteosarcoma (OS). In this study, implants containing DOX, poly(d,l-lactide-co-glycolide), and polyethylene glycol 4000 were prepared by melt-molding method. Then, the antitumor activity and systemic drug distribution of the implants were tested in a K7M2 OS bearing mouse model. The scanning electron microscope images showed that DOX was uniformly dispersed in the polymer matrix. Both the and release profiles of implants are characterized by three-phase release. Implantation of DOX-loaded implants into tumors can inhibit tumor growth in a dose-dependent manner. The pharmacokinetic behavior shows that intratumor chemotherapy through implants has a much higher drug concentration in tumors than in normal tissues, which may be the reason for improving antitumor activity and reducing systemic side effects. In summary, the drug release of the implants prepared in this study is sustained and stable, which promotes long-term local accumulation of drugs in tumors, improves the efficacy of chemotherapy and has low toxicity to normal tissues.
Topics: Animals; Animals, Outbred Strains; Antibiotics, Antineoplastic; Bone Neoplasms; Cell Line, Tumor; Doxorubicin; Drug Implants; Drug Liberation; Female; Male; Mice; Mice, Inbred BALB C; Osteosarcoma; Polyethylene Glycols; Polylactic Acid-Polyglycolic Acid Copolymer; Random Allocation; Rats, Sprague-Dawley; Technology, Pharmaceutical; Xenograft Model Antitumor Assays; Rats
PubMed: 35147071
DOI: 10.1080/10717544.2022.2032878 -
Global Health, Science and Practice Jun 2020The Implants Access Program (IAP) was a partnership between public and private organizations that aimed to increase access to contraceptive implants for women in...
The Implants Access Program (IAP) was a partnership between public and private organizations that aimed to increase access to contraceptive implants for women in low-income countries. The partnership began with 2 volume guarantee agreements that reduced the price of implants by approximately 50% and was complemented by efforts to address supply chain, service delivery, and knowledge and awareness barriers. We conducted a summative evaluation to identify key insights related to the IAP's relevance, effectiveness, and sustainability. We completed a desk review of program materials and published literature, followed by 42 in-depth interviews, including global stakeholders and country stakeholders in 3 case example countries: Kenya, Nigeria, and Uganda. The evaluation found evidence of increased access to implants including a 10-fold increase in procurement between 2010 and 2018 and an increase in prevalence of contraceptive implants during this same period. The IAP leveraged global family planning efforts taking place at the time, and its partnerships offered a business case for manufacturers to support increased access to implants. Enhanced supply chain visibility and coordination helped limit country-level stock-outs, and the IAP built on existing in-country delivery capacity. Although the IAP was able to address key challenges due to its effective collaboration and coordination at global and country levels, sustaining progress requires institutionalized mechanisms to continue global efforts and long-term assurances that the low price of implants will be maintained. Over 6 years, the IAP supported tremendous progress in increasing access to implants for women in low-income countries by building a public- and private-sector collaboration that focused on systems change in the family planning field. This partnership matched a unique response to a unique problem: building tools, systems, and capacity that can inform and support the introduction and scale-up of new and underutilized contraceptive methods.
Topics: Contraception; Contraceptive Agents, Female; Contraceptive Devices; Delayed-Action Preparations; Developing Countries; Drug Implants; Family Planning Services; Female; Health Services Accessibility; Humans; Kenya; Long-Acting Reversible Contraception; Nigeria; Private Sector; Public-Private Sector Partnerships; Uganda
PubMed: 32467126
DOI: 10.9745/GHSP-D-19-00383 -
Scientific Reports Sep 2023Recently, Ta/Cu nanocomposites have been widely used in therapeutic medical devices due to their excellent bioactivity and biocompatibility, antimicrobial property, and...
Recently, Ta/Cu nanocomposites have been widely used in therapeutic medical devices due to their excellent bioactivity and biocompatibility, antimicrobial property, and outstanding corrosion and wear resistance. Since mechanical yielding and any other deformation in the patient's body during treatment are unacceptable in medicine, the characterization of the mechanical behavior of these nanomaterials is of great importance. We focus on the microstructural evolution of Ta/Cu nanocomposite samples under uniaxial tensile loading conditions at different strain rates using a series of molecular dynamics simulations and compare to the reference case of pure Ta. The results show that the increase in dislocation density at lower strain rates leads to the significant weakening of the mechanical properties. The strain rate-dependent plastic deformation mechanism of the samples can be divided into three main categories: phase transitions at the extreme strain rates, dislocation slip/twinning at lower strain rates for coarse-grained samples, and grain-boundary based activities for the finer-grained samples. Finally, we demonstrate that the load transfer from the Ta matrix to the Cu nanoparticles via the interfacial region can significantly affect the plastic deformation of the matrix in all nanocomposite samples. These results will prove useful for the design of therapeutic implants based on Ta/Cu nanocomposites.
Topics: Humans; Nanocomposites; Corrosion; Drug Implants; Edible Grain; Joint Dislocations
PubMed: 37737499
DOI: 10.1038/s41598-023-43126-6 -
Therapeutic Delivery Nov 2014“Despite limitations associated with every approach, delivery of proteins for an extended duration in a controlled manner is achievable… a clinically acceptable...
“Despite limitations associated with every approach, delivery of proteins for an extended duration in a controlled manner is achievable… a clinically acceptable formulation that delivers proteins over a period of months is largely an unmet need.”
Topics: Absorbable Implants; Chemistry, Pharmaceutical; Drug Carriers; Drug Implants; Forecasting; Polymers; Proteins; Technology, Pharmaceutical
PubMed: 25491667
DOI: 10.4155/tde.14.86 -
PloS One 2022This study was carried out to produce low-emitting biomass pellets biofuel from selected forest trees such as (Cedrus deodara and Pinus wallichiana) and agricultural...
This study was carried out to produce low-emitting biomass pellets biofuel from selected forest trees such as (Cedrus deodara and Pinus wallichiana) and agricultural crop residues such as (Zea mays and Triticum aestivum) in Gilgit-Baltistan, Pakistan using indigenously developed technology called pelletizer machine. Characterization, environmental life cycle impact assessment, and cumulative energy demand of biomass pellets biofuel produced from selected agriculture crops and forest tree residues were conducted. The primary data for biomass pellets production was collected by visiting various wood processing factories, sawmills, and agricultural crop fields in the study area. Biomass pellets are a type of biofuel that is often made by compressing sawdust and crushing biomass material into a powdery form. The particles are agglomerated as the raw material is extensively compressed and pelletized. Biomass pellets have lower moisture content, often less than 12%. Physically, the produced pellets were characterized to determine moisture content, pellet dimensions, bulk density, higher heating value, ash content, lower heating value, and element analysis. A functional unit of one kilogram (kg) biomass pellets production was followed in this study.The life cycle impact assessment of one kg biomass pellets biofuel produced from selected agro-forest species revealed environmental impact categories such as acidification (0.006 kg SO2 eq/kg pellets), abiotic depletion (0.018 kg Sb eq/kg pellets), marine aquatic ecotoxicity (417.803 kg 1,4-DB eq/kg pellets), human toxicity (1.107 kg 1,4-DB eq/kg pellets), freshwater aquatic ecotoxicity (0.191 kg 1,4-DB eq/kg pellets), eutrophication (0.001 kg PO4 eq/kg pellets), global warming (0.802 kg CO2 eq/kg pellets), and terrestrial ecotoxicity (0.008 kg 1,4-DB eq/kg pellets). Fossil fuel consumption was the hotspot source to all environmental impacts investigated. To measure the cumulative energy demand of biomass pellets made from different agroforestry species leftovers showed that the maximum cumulative energy was from wheat straw pellets (13.737 MJ), followed by corncob pellets (11.754 MJ), deodar sawdust pellets (10.905 MJ) and blue pine sawdust pellets (10.877 MJ). Among the various production activities, collection and transportation of primary raw material, crushing, screening, adding adhesives, pelletizing, cooling, final screening, and packing have the maximum contribution to the water scarcity index, followed by lubricating oil (0.00147m3). In contrast, the minimum contribution to water footprint was from electricity (0.00008m3) and wheat starch (0.00005m3). The highest contribution to the ecological footprint impact categories such as carbon dioxide, nuclear, and land occupation was lubricating oil and less contribution of wheat starch and electricity for manufacturing one kg pellets biofuel. It is concluded that physico-mechanical and combustion properties of the biomass pellets biofuel developed in the present study were following the Italian recommended standards. Therefore, it is strongly recommended that the Government of Pakistan should introduce the renewable biomass pellets industry in the country to reduce dependency on fossil fuels for cooking and heating purposes.
Topics: Animals; Biofuels; Biomass; Carbon Dioxide; Crops, Agricultural; Fossil Fuels; Humans; Life Cycle Stages; Starch; Water
PubMed: 36206274
DOI: 10.1371/journal.pone.0275005 -
Drug Delivery Nov 2018Along with the development of nanotechnological strategies for biomaterials associated with the prevention of infections, a myriad of clinically unproven techniques have... (Review)
Review
Along with the development of nanotechnological strategies for biomaterials associated with the prevention of infections, a myriad of clinically unproven techniques have been described to date. In this work, the aim was to perform a critical analysis of the literature available concerning antibacterial biomaterials for oral implantology and to provide a practical derivation for such a purpose. As anti-adhesive strategies may affect osseointegration, they should no longer be recommended for inclusion in this class of biomaterials, despite promising results in biomedical engineering for other, non-bone load bearing organs. Targeted, antibacterial drug delivery is most likely desirable in the case of intraosseous implants. Interfering factors such as the oral cavity environment, saliva, the bacterial microbiome, as well as, the characteristics of the alveolar mucosa and peri-implant space must be taken into account when calculating the local pharmacokinetics for antibacterial coatings. Effective release is crucial for tailoring antibacterial implant longevity providing minimal inhibitory concentration (MIC) for the desired amount of time, which for oral implants, should be at least the cumulative time for the osseointegration period and functional loading period within the tissues. These parameters may differ between the implant type and its anatomical site. Also, the functional drug concentration in the peri-implant space should be calculated as the amount of the drug released from the implant surface including the concentration of the drug inactivated by biological fluids of the peri-implant space or saliva flow throughout the effective release time.
Topics: Alveolar Bone Loss; Anti-Bacterial Agents; Biocompatible Materials; Drug Delivery Systems; Drug Implants; Humans; Maxillofacial Prosthesis Implantation; Microbial Sensitivity Tests; Mouth; Osseointegration
PubMed: 29968496
DOI: 10.1080/10717544.2018.1477855 -
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... May 2023The purpose of this study is to evaluate clinical outcomes of autoimmune retinopathy (AIR) in the patients treated with intravitreal dexamethasone implant (IDI).
PURPOSE
The purpose of this study is to evaluate clinical outcomes of autoimmune retinopathy (AIR) in the patients treated with intravitreal dexamethasone implant (IDI).
METHOD
Twenty-one eyes of 11 AIR patients treated with at least 1 injection of IDI were retrospectively reviewed. Clinical outcomes before and after treatment, including best corrected visual acuity (BCVA), optic coherence tomography (OCT), fundus autofluorescence (FAF), full-field electroretinography (ff-ERG), and visual field (VF) at last visit within 6 and/or 12 months, were recorded.
RESULTS
Among all the patients, 3 had cancer-associated retinopathy (CAR) and 8 had non-paraneoplastic-AIR (npAIR) with mean followed up of 8.52 ± 3.03 months (range 4-12 months). All patients achieved improved or stable BCVA within 6 and/or 12 months after the treatment. Cystoid macular edema (CME) in 2 eyes and significant retinal inflammation in 4 eyes were markedly resolved after single injection. Central retinal thickness (CFT) in all eyes without CME, ellipsoid zone (EZ) on OCT in 71.4% of eyes, ERG response in 55% of eyes, and VF in 50% of eyes were stable or improved within 6 months after treatment. At last visit within 12 months, both BCVA and CFT remained stable in the eyes treated with either single or repeated IDI; however, progression of EZ loss and damage of ERG response occurred in some patients with single IDI.
CONCLUSION
Clinical outcomes, including BCVA and parameters of OCT, ERG, and VF, were stable or improved after IDI in a majority of AIR patients. Local treatment of AIR with IDI was a good option to initiate the management or an alternative for the patients' refractory to the systemic therapy but with limited side effect.
Topics: Humans; Dexamethasone; Glucocorticoids; Autoimmune Diseases; Retinal Diseases; Retrospective Studies; Tomography, Optical Coherence; Macular Edema; Retina; Intravitreal Injections; Drug Implants; Diabetic Retinopathy
PubMed: 36565329
DOI: 10.1007/s00417-022-05941-x -
Journal of Glaucoma Sep 2019There is a limit beyond which increasing either the concentration of a prostaglandin analog (PGA) or its dosing frequency fails to produce increases in ocular... (Review)
Review
There is a limit beyond which increasing either the concentration of a prostaglandin analog (PGA) or its dosing frequency fails to produce increases in ocular hypotensive efficacy with topical dosing. Intracameral PGA dosing with a bimatoprost implant, however, does not exhibit the same intraocular pressure (IOP)-lowering plateau at studied concentrations, and the maximum-achievable ocular hypotensive effects are not yet known. This suggests that the bimatoprost intracameral implant may activate another mechanism of action in addition to the mechanism(s) activated by topical application. Episcleral venous pressure (EVP) is a key determinant of IOP, and experimental manipulation of the episcleral vasculature can change both EVP and IOP. The recent observation that topical and intracameral PGA drug delivery routes produce different patterns of conjunctival hyperemia suggested that the differences in the IOP-lowering profiles may be caused by differing effects on the episcleral vasculature. Recent experiments in animals have shown that topical PGAs increase EVP, while the bimatoprost intracameral implant causes a smaller, transient increase in EVP, followed by a sustained decrease. The increase in EVP could be limiting the IOP-lowering efficacy of topical PGAs. In contrast, the decrease in EVP associated with the bimatoprost implant could explain its enhanced IOP-lowering effects. Further research on EVP as a target for IOP lowering is indicated to improve our understanding of this potentially important pathway for treating patients with glaucoma.
Topics: Administration, Ophthalmic; Animals; Antihypertensive Agents; Bimatoprost; Drug Implants; Glaucoma; Humans; Intraocular Pressure; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins, Synthetic; Sclera; Venous Pressure
PubMed: 31261285
DOI: 10.1097/IJG.0000000000001307