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Journal of Controlled Release :... Mar 2022The aim of this study was to better understand to which extent and in which way the presence of an agarose gel (mimicking living tissue) around a PLGA...
The aim of this study was to better understand to which extent and in which way the presence of an agarose gel (mimicking living tissue) around a PLGA [poly(lactic-co-glycolic acid)] implant affects the resulting drug release kinetics. Ibuprofen-loaded implants were prepared by hot melt extrusion. Drug release was measured upon exposure to phosphate buffer pH 7.4 in Eppendorf tubes, as well as upon inclusion into an agarose gel which was exposed to phosphate buffer pH 7.4 in an Eppendorf tube or in a transwell plate. Dynamic changes in the implants' dry & wet mass and dimensions were monitored gravimetrically and by optical macroscopy. Implant erosion and polymer degradation were observed by SEM and GPC. Different pH indicators were used to measure pH changes in the bulk fluids, gels and within the implants during drug release. Ibuprofen release was bi-phasic in all cases: A zero order release phase (~20% of the dose) was followed by a more rapid, final drug release phase. Interestingly, the presence of the hydrogel delayed the onset of the 2nd release phase. This could be attributed to the sterical hindrance of implant swelling: After a certain lag time, the degrading PLGA matrix becomes sufficiently hydrophilic and mechanically instable to allow for the penetration of substantial amounts of water into the system. This fundamentally changes the conditions for drug release: The latter becomes much more mobile and is more rapidly released. A gel surrounding the implant mechanically hinders system swelling and, thus, slows down drug release. These observations also strengthen the hypothesis of the "orchestrating" role of PLGA swelling for the control of drug release and can help developing more realistic in vitro release set-ups.
Topics: Drug Implants; Drug Liberation; Ibuprofen; Phosphates; Polylactic Acid-Polyglycolic Acid Copolymer; Sepharose
PubMed: 35085697
DOI: 10.1016/j.jconrel.2022.01.028 -
Drug Delivery Dec 2022The updating and optimization of drug delivery systems is critical for better behaviors of drugs, as well as for improving impaired implant osseointegration in...
The updating and optimization of drug delivery systems is critical for better behaviors of drugs, as well as for improving impaired implant osseointegration in diabetes. Numerous studies have reported the benefits of exendin-4 on diabetic bone, with the potential to enhance osseointegration in diabetes. To construct an appropriate sustained-release system of exendin-4 targeting implant osseointegration in diabetes, this study fabricated exendin-4-loaded microspheres using poly(lactic-co-glycolic acid) (PLGA) and chitosan. The morphology, size, encapsulation efficiency, and drug release behavior of microspheres were investigated. The bioactivity of drug-loaded microspheres on cell proliferation and osteogenic differentiation of diabetic BMSCs was investigated to examine the pharmacologic action of exendin-4 loaded into chitosan-PLGA microspheres. Further, the influence of microspheres on osseointegration was evaluated using type 2 diabetes mellitus (T2DM) rat implant model. After 4 weeks, the samples were evaluated by radiological and histological analysis. The results of experiments showed that the prepared exendin-4-loaded chitosan-PLGA microspheres have good properties as a drug delivery system, and the chitosan could improve the encapsulation efficiency and drug release of PLGA microspheres. In addition, exendin-4-loaded microspheres could enhance the proliferation and osteogenic differentiation of diabetic BMSCs. The results of experiments showed the exendin-4-loaded microspheres significantly improved the impaired osseointegration and bone formation around implants in T2DM rats without affecting blood glucose levels. Thus, the local application of exendin-4-loaded chitosan-PLGA microspheres might be a promising therapeutic strategy for improving the efficacy of dental implants in T2DM individuals.
Topics: Animals; Cell Proliferation; Chemistry, Pharmaceutical; Delayed-Action Preparations; Diabetes Mellitus, Experimental; Drug Implants; Drug Liberation; Exenatide; Hypoglycemic Agents; Male; Microspheres; Osseointegration; Particle Size; Polylactic Acid-Polyglycolic Acid Copolymer; Random Allocation; Rats; Rats, Sprague-Dawley; Surface Properties
PubMed: 35156499
DOI: 10.1080/10717544.2022.2036873 -
Pharmaceutical Research Jan 2022Drug-filled implants (DFIs) have emerged as an innovative approach to control the delivery of drugs. These devices contain the drug within the structure of the implant...
Drug-filled implants (DFIs) have emerged as an innovative approach to control the delivery of drugs. These devices contain the drug within the structure of the implant itself and avoid the need to include additional drug carrier materials such as a polymers, which are often associated with inflammation and delayed healing/tissue regeneration at the implant site. One common feature of in vitro experiments to generate drug release profiles is stirring or agitation of the release medium. However, the influence of the resulting fluid flow on the rate of drug release from DFIs has yet to be quantified. In this paper we consider two DFIs, which although similar in shape and size, employ different strategies to control the release of drug: a porous pin with pores on the order of μm and a pin drilled with orifices of the order of mm. We develop a multiphysics mathematical model of drug release from these DFIs, subject to fluid flow induced through stirring and show that fluid flow greatly influences the drug release profile for the orifice pin, but that the porous pin drug release profile is relatively insensitive to flow. We demonstrate that drug release from the porous pin may adequately be described through a simplified radial 1D dissolution-diffusion model, while a 3D dissolution-advection-diffusion model is required to describe drug release from the orifice pin. A sensitivity analysis reveals that that the balance of reaction-advection-diffusion in terms of key nondimensional numbers governs the overall drug release. Our findings potentially have important implications in terms of devising the most relevant experimental protocol for quantifying drug release from DFIs.
Topics: Diffusion; Drug Implants; Drug Liberation; Polymers; Porosity
PubMed: 34997423
DOI: 10.1007/s11095-021-03127-4 -
Therapeutic Delivery Feb 2020
Topics: Angiogenesis Inhibitors; Drug Implants; Intravitreal Injections
PubMed: 31914868
DOI: 10.4155/tde-2019-0081 -
Drug Design, Development and Therapy 2017Sustained-release intravitreal 0.7 mg dexamethasone (DEX) implant is approved in Europe for the treatment of macular edema related to diabetic retinopathy, branch... (Review)
Review
Sustained-release intravitreal 0.7 mg dexamethasone (DEX) implant is approved in Europe for the treatment of macular edema related to diabetic retinopathy, branch retinal vein occlusion, central retinal vein occlusion, and non-infectious uveitis. The implant is formulated in a biodegradable copolymer to release the active ingredient within the vitreous chamber for up to 6 months after an intravitreal injection, allowing a prolonged interval of efficacy between injections with a good safety profile. Various other ocular pathologies with inflammatory etiopathogeneses associated with macular edema have been treated by DEX implant, including neovascular age-related macular degeneration, Irvine-Gass syndrome, vasoproliferative retinal tumors, retinal telangiectasia, Coats' disease, radiation maculopathy, retinitis pigmentosa, and macular edema secondary to scleral buckling and pars plana vitrectomy. We undertook a review to provide a comprehensive collection of all of the diseases that benefit from the use of the sustained-release DEX implant, alone or in combination with concomitant therapies. A MEDLINE search revealed lack of randomized controlled trials related to these indications. Therefore we included and analyzed all available studies (retrospective and prospective, comparative and non-comparative, randomized and nonrandomized, single center and multicenter, and case report). There are reports in the literature of the use of DEX implant across a range of macular edema-related pathologies, with their clinical experience supporting the use of DEX implant on a case-by-case basis with the aim of improving patient outcomes in many macular pathologies. As many of the reported macular pathologies are difficult to treat, a new treatment option that has a beneficial influence on the clinical course of the disease may be useful in clinical practice.
Topics: Delayed-Action Preparations; Dexamethasone; Diabetic Retinopathy; Drug Implants; Glucocorticoids; Humans; Intravitreal Injections; Macular Edema; Randomized Controlled Trials as Topic
PubMed: 28860707
DOI: 10.2147/DDDT.S138922 -
Turkish Journal of Ophthalmology Apr 2020We present patient characteristics and follow-up results of cases with anterior chamber dexamethasone implant migration. The common feature of all six presented cases...
We present patient characteristics and follow-up results of cases with anterior chamber dexamethasone implant migration. The common feature of all six presented cases was vitrectomized eyes. Four of the patients had sutured intraocular lens (IOL) implantation due to complicated cataract surgery, one had combined retinal detachment surgery with sutured IOL implantation, and one had vitrectomy for diabetic intravitreal hemorrhage cleaning and uncomplicated cataract surgery. Anterior chamber implant migration caused corneal edema in all cases and elevated intraocular pressure in three cases. In two cases, the dexamethasone implant was directed into the vitreous cavity after maximum pupillary dilation and corneal manipulation with cotton tip applicator with the patient in reverse Trendelenburg position. There was no other complication until dexamethasone implant degradation, with clear cornea at final examination. In two cases, the implant was removed from the anterior chamber by aspiration, but keratoplasty surgery was planned due to endothelial cell loss and persistent corneal edema during follow-up. In the last two cases, the dexamethasone implant was redirected into the vitreous chamber with a 23-gauge catheter and anterior chamber maintainer but they migrated into the anterior chamber again. In one of these patients, the implant was aspirated by catheter and corneal transplantation was performed due to corneal edema, while the other patient's implant was redirected into the vitreous chamber with no further anterior migration. The risk of dexamethasone implants migrating into the anterior chamber of vitrectomized eyes and those with sutured IOL implantation should be kept in mind and the patient should be informed and advised to see an ophthalmologist immediately before permanent corneal endothelial damage occurs.
Topics: Anterior Chamber; Dexamethasone; Drug Implants; Foreign-Body Migration; Humans; Macular Edema; Male; Middle Aged; Tomography, Optical Coherence
PubMed: 32367704
DOI: 10.4274/tjo.galenos.2019.43778 -
TheScientificWorldJournal 2013Decades of research in bioengineering have resulted in the development of many types of 3-dimentional (3D) scaffolds for use as drug delivery systems (DDS) and for... (Review)
Review
Decades of research in bioengineering have resulted in the development of many types of 3-dimentional (3D) scaffolds for use as drug delivery systems (DDS) and for tissue regeneration. Scaffolds may be comprised of different natural fibers and synthetic polymers as well as ceramics in order to exert the most beneficial attributes including biocompatibility, biodegradability, structural integrity, cell infiltration and attachment, and neovascularization. Type I collagen scaffolds meet most of these criteria. In addition, type I collagen binds integrins through RGD and non-RGD sites which facilitates cell migration, attachment, and proliferation. Type I collagen scaffolds can be used for bone tissue repair when they are coated with osteogenic proteins such as bone morphogenic protein (BMP) and bone sialoprotein (BSP). BSP, a small integrin-binding ligand N-linked glycoprotein (SIBLING), has osteogenic properties and plays an essential role in bone formation. BSP also mediates mineral deposition, binds type I collagen with high affinity, and binds α v β 3 and α v β 5 integrins which mediate cell signaling. This paper reviews the emerging evidence demonstrating the efficacy of BSP-collagen scaffolds in bone regeneration.
Topics: Animals; Bone Regeneration; Collagen; Drug Implants; Equipment Design; Humans; Osteoblasts; Sialoglycoproteins; Tissue Scaffolds
PubMed: 23653530
DOI: 10.1155/2013/812718 -
Drug Design, Development and Therapy 2023Fluocinolone acetonide (FAc) intravitreal implant (Iluvien) is a corticosteroid implant indicated for the treatment of diabetic macular oedema (DMO) in patients who have... (Review)
Review
Fluocinolone acetonide (FAc) intravitreal implant (Iluvien) is a corticosteroid implant indicated for the treatment of diabetic macular oedema (DMO) in patients who have previously received conventional treatment without good response, non-infectious posterior uveitis, and as an off-label treatment of the macular oedema secondary to retinal vein occlusion. FAc is a non-biodegradable 0.19 mg intravitreal implant which is designed to release FAc over 3 years at a rate of approximately 0.2 mcg per day. The aim of this review is to describe the special pharmacological properties of Iluvien and display the outcomes of the most important clinical trials and real-world studies regarding its efficacy and safety for the management of the above retinal disorders.
Topics: Humans; Diabetic Retinopathy; Drug Implants; Fluocinolone Acetonide; Glucocorticoids; Intravitreal Injections; Macular Edema; Retinal Diseases; Anti-Inflammatory Agents
PubMed: 37020801
DOI: 10.2147/DDDT.S403259 -
Advanced Drug Delivery Reviews Sep 2012Many surgical procedures require the placement of an inert or tissue-derived implant deep within the body cavity. While the majority of these implants do not become... (Review)
Review
Many surgical procedures require the placement of an inert or tissue-derived implant deep within the body cavity. While the majority of these implants do not become colonized by bacteria, a small percentage develops a biofilm layer that harbors invasive microorganisms. In orthopaedic surgery, unresolved periprosthetic infections can lead to implant loosening, arthrodeses, amputations and sometimes death. The focus of this review is to describe development of an implant in which an antibiotic tethered to the metal surface is used to prevent bacterial colonization and biofilm formation. Building on well-established chemical syntheses, studies show that antibiotics can be linked to titanium through a self-assembled monolayer of siloxy amines. The stable metal-antibiotic construct resists bacterial colonization and biofilm formation while remaining amenable to osteoblastic cell adhesion and maturation. In an animal model, the antibiotic modified implant resists challenges by bacteria that are commonly present in periprosthetic infections. While the long-term efficacy and stability is still to be established, ongoing studies support the view that this novel type of bioactive surface has a real potential to mitigate or prevent the devastating consequences of orthopaedic infection.
Topics: Animals; Anti-Bacterial Agents; Biofilms; Disease Models, Animal; Drug Delivery Systems; Drug Design; Drug Implants; Humans; Orthopedic Procedures; Prostheses and Implants; Prosthesis Design; Prosthesis-Related Infections; Titanium
PubMed: 22512927
DOI: 10.1016/j.addr.2012.03.015 -
BioMed Research International 2016With the objective of improving efficacy and morbidity, device manufacturers incorporate chemicals or drugs into medical implants. Using multiple reservoirs of discrete... (Review)
Review
With the objective of improving efficacy and morbidity, device manufacturers incorporate chemicals or drugs into medical implants. Using multiple reservoirs of discrete drug doses, microchips represent a new technology capable of on-demand release of various drugs over long periods of time. Herein, we review drug delivery systems, how microchips work, recent investigations, and future applications in various fields of medicine.
Topics: Drug Delivery Systems; Drug Implants; Drug Liberation; Humans; Lab-On-A-Chip Devices; Pharmaceutical Preparations
PubMed: 27376079
DOI: 10.1155/2016/1743472