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Journal of Acquired Immune Deficiency... Jul 2021Long-acting pre-exposure prophylaxis (LA-PrEP) formulated as implants and injections are promising prevention method strategies offering simplicity, discretion, and long...
BACKGROUND
Long-acting pre-exposure prophylaxis (LA-PrEP) formulated as implants and injections are promising prevention method strategies offering simplicity, discretion, and long dose duration. Men are important end users of LA-PrEP, and early assessment of their preferences could enhance downstream male engagement in HIV prevention.
METHODS
A discrete-choice experiment survey was conducted with 406 men, aged 18-24, in Cape Town, South Africa, to assess preferences for 5 LA-PrEP attributes with 2-4 pictorially-depicted levels: delivery form, duration, insertion location, soreness, and delivery facility. Latent class analysis was used to explore heterogeneity of preferences and estimate preference shares.
RESULTS
The median age was 21 (interquartile range 19-22), and 47% were men who have sex with men. Duration was the most important product attribute. Latent class analysis identified 3 classes: "duration-dominant decision makers" (46%) were the largest class, defined by significant preference for a longer duration product. "Comprehensive decision makers" (36%) had preferences shaped equally by multiple attributes and preferred implants. "Injection-dominant decision makers" (18%) had strong preference for injections (vs. implant) and were significantly more likely to be men who have sex with men. When estimating shares for a 2-month injection in the buttocks with mild soreness (HPTN regimen) vs. a 6-month implant (to arm) with moderate soreness (current target), 95% of "injection-dominant decision makers" would choose injections, whereas 79% and 63% of "duration-dominant decision makers" and "comprehensive decision makers" would choose implant.
CONCLUSIONS
Young South African men indicated acceptability for LA-PrEP. Preferences were shaped mainly by duration, suggesting a sizeable market for implants, and underscoring the importance of product choice. Further research into men's acceptability of LA PrEP strategies to achieve engagement in these HIV prevention tools constitutes a priority.
Topics: Adolescent; Anti-HIV Agents; Data Collection; Delayed-Action Preparations; Drug Implants; HIV Infections; HIV-1; Humans; Male; Patient Preference; South Africa; Young Adult
PubMed: 33633031
DOI: 10.1097/QAI.0000000000002670 -
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 -
Cell Biology International Aug 2021Metallic materials are commonly used for load-bearing implants and as internal fixation devices. It is customary to use austenitic stainless steel, especially surgical... (Review)
Review
Metallic materials are commonly used for load-bearing implants and as internal fixation devices. It is customary to use austenitic stainless steel, especially surgical grade type 316L SS as temporary and Ti alloys as permanent implants. However, long-term, poor bonding with bone, corrosion, and release of metal ions, such as chromium and nickel occur. These ions are powerful allergens and carcinogens and their uncontrolled leaching may be avoided by surface coatings. Therefore, bioactive glasses (BGs) became a vital biomedical material, which can form a biologically active phase of hydroxycarbonate apatite on their surface when in contact with physiological fluids. To reduce the high coefficient of friction and the brittle nature of BGs, polymers are normally incorporated to avoid the high-temperature sintering/densification of ceramic-only coatings. For medical application, electrophoretic deposition (EPD) is now used for polymer (organic) and ceramic (inorganic) components at room temperature due to its simplicity, control of coating thickness and uniformity, low cost of equipment, ability to coat substrates of intricate shape and to supply thick films in composite form, high purity of deposits as well as no phase transformation during coating. Although extensive research has been conducted on polymer/inorganic composite coatings, only some studies have reported multifunctional properties, such as biological antibacterial activity, enhanced cell adhesion, controlled drug release ability, and mechanical properties. This review will focus on biodegradable coatings, including zien, chitosan, gelatin, cellulose loaded with antibacterial drugs/metallic ions/natural herbs on biostable substrates (PEEK/PMMA/PCL/PLLA layers), which have the potential of multifunctional coating for metallic implants.
Topics: Alloys; Animals; Anti-Bacterial Agents; Biocompatible Materials; Chitosan; Drug Implants; Gelatin; Humans; Materials Testing; Metals
PubMed: 33818836
DOI: 10.1002/cbin.11604 -
Contraception Jul 2023Rifampin, a strong CYP3A inducer, is the gold standard for evaluating CYP3A-mediated drug-drug interactions. We aimed to evaluate the pharmacokinetic and pharmacodynamic...
OBJECTIVES
Rifampin, a strong CYP3A inducer, is the gold standard for evaluating CYP3A-mediated drug-drug interactions. We aimed to evaluate the pharmacokinetic and pharmacodynamic effects of a short course (2 weeks) of rifampin on serum etonogestrel (ENG) concentrations and serologic measures of ovarian activity (endogenous estradiol [E2] and progesterone [P4]) among ENG implant users.
STUDY DESIGN
We enrolled healthy females using ENG implants for 12 to 36 months. We measured baseline serum ENG concentrations using a validated liquid chromatography mass-spectrometry assay and baseline E2 and P4 concentrations using chemiluminescent immunoassays. After 2 weeks of rifampin 600 mg daily, we repeated ENG, E2, and P4 measurements. We compared pre- and post-rifampin serum measurements using paired Wilcoxon signed-rank tests.
RESULTS
Fifteen participants completed all study procedures. Participants' median age was 28.2 years (range 21.8-34.1), median body-mass index was 25.2 kg/m (range 18.9-37.3), and median duration of implant use was 22 months (range 12-32). All participants experienced significant decreases from baseline ENG concentrations (median 164.0 pg/mL [range 94.4-265.0]) to post-rifampin measurements (median 47.8 pg/mL [range 24.7-82.8]) (p < 0.001). Serum E2 concentrations also significantly increased with rifampin exposure (median 73 pg/mL vs 202 pg/mL, p = 0.003); increases in serum P4 concentrations were not statistically significant (p = 0.19). Three participants (20%) experienced increased luteal activity, with one presumptively ovulating post-rifampin (P4 = 15.8 ng/mL).
CONCLUSIONS
With only short exposure to a strong CYP3A inducer, ENG implant users experienced clinically significant decreases in serum ENG concentrations that led to changes in biomarkers indicative of waning suppression of ovulation.
IMPLICATIONS
Even a short, 2-week course of treatment with rifampin places etonogestrel contraceptive implant users at risk for decreased contraceptive efficacy. Clinicians should counsel patients using etonogestrel implants considering any duration of rifampin therapy on the need for backup nonhormonal contraception or the use of an intrauterine device to avoid unintended pregnancies.
Topics: Pregnancy; Female; Humans; Young Adult; Adult; Contraceptive Agents, Female; Rifampin; Cytochrome P-450 CYP3A Inducers; Drug Implants; Desogestrel; Ovulation; Biomarkers
PubMed: 36997081
DOI: 10.1016/j.contraception.2023.110035 -
Postgraduate Medicine Nov 2020Invasive interventional procedures for managing pain in cancer patients are often underutilized following the popularization of the WHO analgesic ladder. The procedures... (Review)
Review
Invasive interventional procedures for managing pain in cancer patients are often underutilized following the popularization of the WHO analgesic ladder. The procedures that were successfully used until then were relegated away from mainstream palliative care practice, with the advent of newer opioids and adjuvants. Even though nerve blocks, intrathecal pumps and spinal cord stimulation were reintroduced as the fourth step of the WHO ladder, often referrals for these procedures are too late to produce a meaningful effect on quality of life. At this point most patients have advanced disease and are requiring end of life care. Additionally, it is becoming evident that at least 10% of patients do not achieve good quality analgesia with oral opioids and are often troubled by unacceptable side effects. There is an increasing public awareness of the problems with long-term opioid therapy and some of these patients would certainly benefit from invasive procedures to alleviate their pain and improve their quality of life. Improving life quality and expectancy with better treatment options and increasing number of cancer survivors should be heralding a change and hence neurolytic procedures are to be used only in patients with limited life expectancy. ITDDs, neuromodulation and ever-increasing use of procedures routinely used in treating chronic nonmalignant pain would be the mainstay of interventional management until AI and nanotechnology would open doors for novel treatment options. Interventions should not be used as a last resort after multiple failed attempts at opioid therapy, but as an integral part of a management strategy including medical management, psychological and emotional welfare, and supportive care of the patient in a holistic manner. The curriculum of specialists should include appropriate training to safely perform and produce better quality evidence to validate the efficacy and safety of these challenging procedures.
Topics: Ablation Techniques; Cancer Pain; Drug Implants; Humans; Nerve Block; Pain Management; Palliative Care; Quality of Life
PubMed: 32799614
DOI: 10.1080/00325481.2020.1807796 -
European Journal of Pharmaceutics and... Aug 2022The aim of this study was to better understand the importance of the diameter of poly(lactic-co-glycolic acid) (PLGA)-based implants on system performance, in particular...
The aim of this study was to better understand the importance of the diameter of poly(lactic-co-glycolic acid) (PLGA)-based implants on system performance, in particular the control of drug release. Different types of ibuprofen-loaded implants were prepared by hot melt extrusion using a Leistritz Nano 16 twin-screw extruder. Drug release was measured in well agitated phosphate buffer pH7.4 bulk fluid and in agarose gels in Eppendorf tubes or transwell plates. Dynamic changes in the implants' dry & wet mass, volume, polymer molecular weight as well as inner & outer morphology were monitored using gravimetric analysis, optical macroscopy, gel permeation chromatography and scanning electron microscopy. The physical states of the drug and polymer were determined by DSC. Also pH changes in the release medium were investigated. Irrespective of the type of experimental set-up, the resulting absolute and relative drug release rates decreased with increasing implant diameter (0.7-2.8 mm). Bi-phasic drug release was observed in all cases from the monolithic solutions (ibuprofen was dissolved in the polymer): A zero order release phase was followed by a final, rapid drug release phase (accounting for 80-90% of the total drug dose). The decrease in the relative drug release rate with increasing system diameter can be explained by the increase in the diffusion pathway lengths to be overcome. Interestingly, also the onset of the final rapid drug release phase was delayed with increasing implant diameter. This can probably be attributed to the higher mechanical stability of thicker devices, offering more resistance to substantial entire system swelling.
Topics: Drug Implants; Drug Liberation; Ibuprofen; Polylactic Acid-Polyglycolic Acid Copolymer; Polymers
PubMed: 35659920
DOI: 10.1016/j.ejpb.2022.05.020 -
Promising Approach in the Treatment of Glaucoma Using Nanotechnology and Nanomedicine-Based Systems.Molecules (Basel, Switzerland) Oct 2019Glaucoma is considered a leading cause of blindness with the human eye being one of the body's most delicate organs. Ocular diseases encompass diverse diseases affecting... (Review)
Review
Glaucoma is considered a leading cause of blindness with the human eye being one of the body's most delicate organs. Ocular diseases encompass diverse diseases affecting the anterior and posterior ocular sections, respectively. The human eye's peculiar and exclusive anatomy and physiology continue to pose a significant obstacle to researchers and pharmacologists in the provision of efficient drug delivery. Though several traditional invasive and noninvasive eye therapies exist, including implants, eye drops, and injections, there are still significant complications that arise which may either be their low bioavailability or the grave ocular adverse effects experienced thereafter. On the other hand, new nanoscience technology and nanotechnology serve as a novel approach in ocular disease treatment. In order to interact specifically with ocular tissues and overcome ocular challenges, numerous active molecules have been modified to react with nanocarriers. In the general population of glaucoma patients, disease growth and advancement cannot be contained by decreasing intraocular pressure (IOP), hence a spiking in future research for novel drug delivery systems and target therapeutics. This review focuses on nanotechnology and its therapeutic and diagnostic prospects in ophthalmology, specifically glaucoma. Nanotechnology and nanomedicine history, the human eye anatomy, research frontiers in nanomedicine and nanotechnology, its imaging modal quality, diagnostic and surgical approach, and its possible application in glaucoma will all be further explored below. Particular focus will be on the efficiency and safety of this new therapy and its advances.
Topics: Animals; Biological Availability; Drug Delivery Systems; Drug Implants; Drug Liberation; Glaucoma; Humans; Intraocular Pressure; Mice; Nanomedicine; Rabbits; Tomography, Optical Coherence; Trabecular Meshwork
PubMed: 31652593
DOI: 10.3390/molecules24203805 -
International Journal of Pharmaceutics Apr 2023Fabricating a multifunctional orthopedic implant which prevents post-surgery infection is highly desirable in advanced materials applications. However, designing an...
Fabricating a multifunctional orthopedic implant which prevents post-surgery infection is highly desirable in advanced materials applications. However, designing an antimicrobial implant, which simultaneously promotes a sustained drug release and satisfactory cell proliferation, remains a challenge. The current study presents a drug-loaded surface-modified titanium nanotube (TNT) implant with different surface chemistry which was developed to investigate the effect of surface coating on drug release, antimicrobial activity, and cell proliferation. Accordingly, sodium alginate and chitosan were coated on the surface of TNT implants with different coating orders through layer-by-layer assembly. The coatings' swelling ratio and degradation rate were around 613% and 75%, respectively. The drug release results showed that surface-coatings prolonged the releasing profile for about 4 weeks. Chitosan coated TNTs demonstrated greater inhibition zone at 16.33mm compared with the other samples where no inhibition zone was observed. However, chitosan and alginate coated TNTs exhibited smaller inhibition zones at 48.56mm and 43.28mm, respectively, compared to bare TNT, which can be attributed to the coatings preventing the antibiotic burst release. Higher viability of cultured osteoblast cells was observed for chitosan-coated TNT as the top layer compared to the bare TNT at 12.18%, indicating improved bioactivity of TNT implants when the chitosan has the most contact with cells. Coupled with the cell viability assay, molecular dynamics (MD) simulations were carried out by placing collagen and fibronectin near the considered substrates. In agreement with cell viability results, MD simulations also indicated that chitosan had the highest adsorption energy approximately 60Kcal/mol. In summary, the proposed bilayer chitosan-coated drug-loaded TNT implant with chitosan and sodium alginate coating as the top and the bottom layers, respectively, can be a potential candidate for orthopedic applications in the light of its bacterial biofilm prevention, better osteoconductivity, and providing an adequate drug release profile.
Topics: Gentamicins; Titanium; Chitosan; Surface Properties; Anti-Bacterial Agents; Drug Implants; Nanotubes; Alginates; Coated Materials, Biocompatible
PubMed: 36889413
DOI: 10.1016/j.ijpharm.2023.122764 -
Annals of Biomedical Engineering May 2023There is a growing number of protein drugs, yet their limited oral bioavailability requires that patients receive frequent, high dose injections. In situ forming...
There is a growing number of protein drugs, yet their limited oral bioavailability requires that patients receive frequent, high dose injections. In situ forming implants (ISFIs) for controlled release of biotherapeutics have the potential to greatly reduce the injection frequency and improve patient compliance. However, protein release from ISFIs is a challenge due to their proclivity for instability. Specifically, factors such as the acidic microclimate within ISFIs can lead to protein aggregation and denaturation. Basic salts have been shown in PLGA microparticle and microcylinder formulations to significantly reduce protein instability by neutralizing this acidic environment. The overall objective of the study was to demonstrate that basic salts can be used with an ISFI system to neutralize the implant acidification. To this end, the basic salts MgCO3 and Mg(OH)2 were added to a protein-releasing ISFI and the effect on drug release, pH, implant swelling, implant diffusivity, and implant erosion were evaluated. Either salt added at 3 wt% neutralized the acidic environment surrounding the implants, keeping the pH at 6.64 ± 0.03 (MgCO) and 6.46 ± 0.11 (Mg(OH)) after 28 day compared to 3.72 ± 0.05 with no salts added. The salts initially increased solution uptake into the implants but delayed implant degradation and erosion. The 3 wt% Mg(OH) formulation also showed slightly improved drug release with a lower burst and increased slope. We showed that salt additives can be an effective way to modulate the pH in the ISFI environment, which can improve protein stability and ultimately improve the capacity of ISFIs for delivering pH-sensitive biomolecules. Such a platform represents a low-cost method of improving overall patient compliance and reducing the overall healthcare burden.
Topics: Humans; Drug Implants; Drug Liberation; Prostheses and Implants
PubMed: 36454398
DOI: 10.1007/s10439-022-03109-6 -
International Journal of Pharmaceutics Jun 2022In situ forming implants are injectable liquid formulations which form solid or semisolid depots following injection. This allows for minimally invasive administration,...
In situ forming implants are injectable liquid formulations which form solid or semisolid depots following injection. This allows for minimally invasive administration, localized drug delivery, and extended drug release. Unfortunately, this drug delivery strategy lacks standardized in vitro dissolution methods due to the difficulties in recreating implant formation in vitro that is biomimicry and with reproducible and controllable shape and dimensions. In the present study, an innovative, adapter-based in vitro release testing method was developed to solve this problem. Two distinctively different in situ forming implants (a risperidone formulation (suspension) consisting of PLGA dissolved in N-methyl pyrrolidone (NMP), where risperidone powder was suspended to form a drug suspension, and a naproxen formulation (solution) consisting of PLGA dissolved in NMP, where naproxen was completely dissolved to form a solution), were used as model in situ-forming implants. The results revealed that the implants formed in the custom-designed adapter with a water-dissolvable polyvinyl alcohol (PVA) film were bio-mimicking and reproducible in both shape and burst release of drug according to rabbit data. For both the suspension and solution formulations, this adapter-based in vitro release testing method resulted in consistent release data. Compared with a direct injection in vitro release testing method, the release profiles generated using the adapter-based method were capable of distinguishing the different release phases (initial release within 24 h, diffusion-facilitated release, and degradation-controlled release). In addition, the adapter-based method could discriminate formulation and dissolution apparatus changes and could be utilized to develop accelerated release testing methods. This adapter-based method has the promise of wide use in release testing of in situ forming implant formulations and has the potential to be used in the development of in vivo-predictive in vitro release methods.
Topics: Animals; Drug Implants; Drug Liberation; Naproxen; Pharmaceutical Preparations; Polylactic Acid-Polyglycolic Acid Copolymer; Rabbits; Risperidone
PubMed: 35489601
DOI: 10.1016/j.ijpharm.2022.121777