Concept Of Drug Delivery Research Articles

Porous silica microshells from diatoms as biocarrier for drug delivery applications

The use of porous silica microshells (microparticles) generated from fossilised diatoms known as diatomite or diatomaceous earth (DE) as a natural drug carrier for drug delivery application is presented. The structure, morphology, particle size distribution, porosity, surface area and crystallinity of diatom microshells obtained from Australian mine (Mount Sylvia Diatomite Pty. Ltd.) were characterised using scanning electron microscopy, particle size measurements, BET analysis and X-ray powder diffraction analysis. To prove the drug delivery concept based on diatoms for implant and oral drug delivery, indomethacin as a model of water poorly soluble drug was investigated. Results show the effectiveness of diatom silica for drug delivery application, with about 22wt.% drug loading capacity and sustained drug release over two weeks. Two steps drug release from diatom structures were observed: the first is rapid release (over 6h) attributed to the surface deposited drug and the second is slow and sustained release over two weeks with zero order kinetics, as a result of release from diatom pores and internal hollow structure. These results confirm that natural material based on diatom silica can be successfully applied as a biocarrier for both oral and implant drug delivery applications, offering considerable potential to replace synthetic silica based materials.

Efficacy of clobetasol spray: Factors beyond patient compliance

Clobetasol 0.05% spray, a topical clobetasol propionate, is a non-greasy formulation that has shown increased clinical efficacy in a head-to-head comparison with foam formulation. Moreover, available data from randomized, controlled, double-blind trials suggests that clobetasol spray is, in fact, slightly more effective than most, if not all, other preparations of clobetasol. The fact that clobetasol spray is exceptionally easy to comply with may have played a major role in this outcome; however, other factors must be considered. These include vehicle metamorphosis post-application as well as vehicle and excipient effects on stratum corneum permeability. Basic concepts in topical drug delivery and how they apply to this spray vehicle may further explain the greater efficacy of clobetasol spray.

Novel free paclitaxel-loaded poly(L-γ-glutamylglutamine)–paclitaxel nanoparticles

The purpose of this study was to develop a novel formulation of paclitaxel (PTX) that would improve its therapeutic index. Here, we combined a concept of polymer–PTX drug conjugate with a concept of polymeric micelle drug delivery to form novel free PTX-loaded poly(L-γ-glutamylglutamine) (PGG)–PTX conjugate nanoparticles. The significance of this drug formulation emphasizes the simplicity, novelty, and flexibility of the method of forming nanoparticles that contain free PTX and conjugated PTX in the same drug delivery system. The results of effectively inhibiting tumor growth in mouse models demonstrated the feasibility of the nanoparticle formulation. The versatility and potential of this dual PTX drug delivery system can be explored with different drugs for different indications. Novel and simple formulations of PTX-loaded PGG–PTX nanoparticles could have important implications in translational medicines.

Passive targeting of ischemic myocardium with the use of silica nanoparticles

The clinical outcome in patients with ischemic heart disease can be significantly improved with the implementation of targeted drug delivery directly into the ischemic myocardium. In this study we describe the concept of heart-targeted drug delivery with the use of silica nannocarriers. The techniques of nanoparticle functionalization, as well as the data on the effects that silica nanoparticle formulations have on the parameters of systemic hemodynamics, are also presented. The natural biodistribution of fluorescein- and indocyanine green-labeled silica nanoparticles was studied with the use of optical fluorescence. We showed in the study that silica nanoparticles accumulated in the ischemic-reperfused area of the heart, thus providing the first experimental evidence for passive heart targeting. In conclusion, silica nanoparticles are prospective drug carriers that have no toxic effect during acute intravenous administration.

Konzept eines druckgesteuerten Mikrostents für die Glaukomtherapie

A pressure-controlled microstent could permanently normalise the intraocular pressure (IOP) for open-angle glaucoma therapy by drainage into the suprachoroidal space. The complex requirements demand new technical solutions as well as an improved understanding of specific cell biological processes at the implant's surface to develop effective local drug delivery (LDD) concepts and surface modifications. Fluid mechanical requirements were derived from physiological data and the analysis of commercial glaucoma implants. The technological basics for the production of suitable structures are refined ultra-short pulse laser technology and 2-photon polymerisation (2PP). All known glaucoma implants induce unwanted cell proliferation resulting in a loss of function. It is assumed that the activity of fibroblasts is low in the suprachoroidal space. However, it was seen that LDD concepts are required to control cell proliferation. Fibroblasts from sclera and choroidea were isolated und cultured as the most relevant cell types for in vitro investigation. Potential materials and drugs were investigated by cell viability tests for biocompatibility or suppression of cell viability. The fluid mechanical analysis leads to smallest stent lumina (ID = 50 µm) at anatomically suitable implant lengths (7 - 10 mm). Only pressure control can manage the individual conditions with changing IOP. Finite element analysis of valves showed the need for highly flexible structures. This can be achieved by combining basic structures with micromechanically active valves added by 2PP. The potential materials show perfect in vitro and in vivo biocompatibility. Ormocers which are best suited for 2PP are also highly biocompatible. The selected drugs paclitaxel and triamcinolon acetonide open a wide therapeutic window to impair fibroblast growth. The surgical procedure was established by implantation of prototypes in rabbit eyes, connecting the anterior chamber with the suprachoroidal space. Highly flexible implants are required for correct placement within the eye. The new concept of the microstent combines biomechanical approaches, technologies for microfabrication and current LDD concepts and opens new perspectives for glaucoma therapy.

Mycoplasma pneumoniae Mpn133 is a cytotoxic nuclease with a glutamic acid-, lysine- and serine-rich region essential for binding and internalization but not enzymatic activity

We identified Mpn133 as a Ca(2+)-dependent cytotoxic nuclease of Mycoplasma pneumoniae. Flow cytometry analysis and immunofluorescence studies revealed the binding and internalization of recombinant Mpn133 (rMpn133) in human airway A549 cells. Amino acid sequence comparisons of Mpn133 with other mycoplasma nucleases demonstrated the presence of a unique glutamic acid-, lysine- and serine-rich region (EKS region; amino acids 72-110). Deletion of this EKS peptide (rMpn133(Δ72-110)) abrogated its binding and internalization but not its nuclease activity. The function of the EKS region in host cell trafficking and nuclear localization was reinforced by the successful delivery of EKS-conjugated mCherry protein into A549 cells. rMpn133, but not rMpn133(Δ72-110), induced apoptosis-like death in A549 cells. This observation suggested a unique role of Mpn133 as an important contributor to M. pneumoniae-associated life cycle events and as a virulence factor in host-associated cytopathologies. In addition, the distinct property of the EKS peptide in delivery of proteins, like mCherry, into target cells opens new avenues to the establishment of novel concepts of drug delivery and therapy.

Enriching lipid nanovesicles with short‐chain glucosylceramide improves doxorubicin delivery and efficacy in solid tumors

For amphiphilic anticancer drugs, such as the anthracyclin doxorubicin (Dox), uptake by tumor cells involves slow diffusion across the plasma membrane, a limiting factor in clinical oncology. Previously, we discovered that preinsertion of short-chain sphingolipids such as N-octanoyl-glucosylceramide (GC) in the tumor cell membrane enhances cellular Dox uptake. In the present study, we apply this strategy in vitro and in vivo by coadministering GC and Dox in a lipid nanovesicle (LNV). GC enrichment of Dox-LNVs strongly enhanced in vitro cytotoxicity toward B16 melanoma and A431 carcinoma, as evidenced by 6-fold decreased IC(50) values compared with Dox-LNVs. This correlated with enhanced cellular Dox uptake observed by confocal microscopy. Intravital optical imaging in window chamber-bearing mice with orthotopically implanted B16 melanoma demonstrated enhanced GC-mediated Dox delivery to tumor cells. Treatment of nude mice bearing human A431 xenografts with 6 mg/kg GC-Dox-LNVs almost doubled the tumor growth delay compared with Dox-LNVs. A second administration of 5 mg/kg after 3 d induced even 3-fold delay in tumor growth, while no systemic toxicity was found. GC-enriched Dox-LNVs displayed superior in vitro and in vivo antitumor activity, without systemic toxicity. This new drug delivery concept, aiming at increased membrane permeability for amphiphilic drugs, provides an opportunity to improve cancer chemotherapy.

Drug-Coated Balloons for the Prevention of Vascular Restenosis

From early in the history of percutaneous cardiovascular intervention, restenosis has been one of the most important clinical and biological measures of success, and a great deal of effort has been put into understanding the mechanisms responsible.1,2 Restenosis is the result of the interaction of a variety of mechanical and biological processes that begin immediately after balloon injury, including early vessel recoil,3,4 negative vascular remodeling,5 and excessive neointimal proliferation.5–7 The most important limitations of balloon angioplasty, abrupt vessel closure resulting from elastic recoil and occlusive plaque dissection, were effectively solved by the introduction of balloon-expandable stents.8 However, in-stent restenosis (ISR), the result of the initial injury and the vascular response to the implanted metallic prosthesis leading to excessive neointimal proliferation, remained as the most important cause of failure of these devices.9,10 Drug-eluting stents (DES) effectively reduced ISR by addressing the biological mechanisms of neointimal proliferation and have become the mainstay of the interventional treatment of coronary atherosclerotic disease.11 However, the demonstrated efficacy of DES is balanced by the small but unpredictable risk of very late stent thrombosis thought to be due to delayed vascular healing resulting from either the initial antiproliferative effect (and associated late acquired incomplete stent apposition) or a hypersensitivity reaction to the drug, polymer coating, or their combination.12,13 Moreover, beyond the coronary vasculature, there has been a paucity of effective therapies to manage restenosis after intervention. In recent years, drug-coated balloons (DCBs) have emerged as a therapeutic alternative in the interventional field.14 With this technology, short-term transfer of antiproliferative drugs to the arterial wall is achieved without the requirement of an implanted drug delivery system, thus potentially reducing the untoward effects associated with polymer-based stent technologies. In small clinical randomized trials, paclitaxel-coated balloons have been shown to be …

The importance of preclinical research in contemporary interventional cardiology

Historical overview of preclinical science Preclinical animal models provide a powerful tool for assessing vascular biology in cardiovascular medicine. In the search for reliable models that mirror the essential vascular effects of local drug delivery concepts, several animal species were evaluated during the past decades. One of the earliest successful models in interventional cardiology – the swine model of coronary artery stenting – has best stood the test of time1. In the era of drug eluting stents (DES), the rabbit iliac artery stenting model became established as a second appropriate model for the study of vascular responses to stent implantation2,3. More recent preclinical studies have again focused on using smaller animal models (rat and mouse) for evaluating stent implants as they provide the opportunity to assess basic molecular mechanisms of stent healing4,5. These models require smaller devices with adapted stent designs, and therefore their translational applicability for the assessment of human device safety is limited. Nevertheless, they may serve as important complementary tools due to the great advantage of utilising genetically engineered strains and the specific insights provided into pathophysiologic mechanisms.

CFD simulations of enhanced condensational growth (ECG) applied to respiratory drug delivery with comparisons to in vitro data

Enhanced condensational growth (ECG) is a newly proposed concept for respiratory drug delivery in which a submicrometer aerosol is inhaled in combination with saturated or supersaturated water vapor. The initially small aerosol size provides for very low extrathoracic deposition, whereas condensation onto droplets in vivo results in size increase and improved lung retention. The objective of this study was to develop and evaluate a CFD model of ECG in a simple tubular geometry with direct comparisons to in vitro results. The length (29 cm) and diameter (2 cm) of the tubular geometry were representative of respiratory airways of an adult from the mouth to the first tracheobronchial bifurcation. At the model inlet, separate streams of humidified air (25, 30, and 39 °C) and submicrometer aerosol droplets with mass median aerodynamic diameters (MMADs) of 150, 560, and 900 nm were combined. The effects of condensation and droplet growth on water vapor concentrations and temperatures in the continuous phase (i.e., two-way coupling) were also considered. For an inlet saturated air temperature of 39 °C, the two-way coupled numerical (and in vitro) final aerosol MMADs for initial sizes of 150, 560, and 900 nm were 1.75 μm (vs. 1.23 μm), 2.58 μm (vs. 2.66 μm), and 2.65 μm (vs. 2.63 μm), respectively. By including the effects of two-way coupling in the model, agreements with the in vitro results were significantly improved compared with a one-way coupled assumption. Results indicated that both mass and thermal two-way coupling effects were important in the ECG process. Considering the initial aerosol sizes of 560 and 900 nm, the final sizes were most influenced by inlet saturated air temperature and aerosol number concentration and were not largely influenced by initial size. Considering the growth of submicrometer aerosols to above 2 μm at realistic number concentrations, ECG may be an effective respiratory drug delivery approach for minimizing mouth–throat deposition and maximizing aerosol retention in a safe and simple manner. However, future studies are needed to explore effects of in vivo boundary conditions, more realistic respiratory geometries, and transient breathing.

Novel technologies of oral controlled release drug delivery system

oral drug delivery technologies have emerged and expanded into different drug delivery systems with different drug release mechanisms in the last few decades. Sophisticated instrumentation, modern mathematical models and computational power have revolutionized the entire process of formulation and development of drug delivery systems and advanced the concept of drug delivery from a simple pill to a programmable, time controlled smart system. In situ forming oral controlled release formulation is a new technology in the field of oral controlled release delivery systems. The concept of in situ forming devices (ISFD) entered the pharmaceutical field in the early 1980s as parenteral controlled release dosage forms. In the last decade, this technology has grown significantly due to its potential advantages compared to the traditional parenteral controlled release dosage forms. However, a review of literature revealed that there are not many publications describing the usage of this technology for oral controlled release formulations. How to Cite this Article Pubmed Style Patel RR, Patel JK. Technologies of Oral Controlled Release Drug Delivery SRP. 2010; 1(2): 128-132. doi:10.4103/0975-8453.75054 Web Style Patel RR, Patel JK. Technologies of Oral Controlled Release Drug Delivery http://www.sysrevpharm.org/?mno=302644616 [Access: March 28, 2021]. doi:10.4103/0975-8453.75054 AMA (American Medical Association) Style Patel RR, Patel JK. Technologies of Oral Controlled Release Drug Delivery SRP. 2010; 1(2): 128-132. doi:10.4103/0975-8453.75054 Vancouver/ICMJE Style Patel RR, Patel JK. Technologies of Oral Controlled Release Drug Delivery SRP. (2010), [cited March 28, 2021]; 1(2): 128-132. doi:10.4103/0975-8453.75054 Harvard Style Patel RR, Patel JK (2010) Technologies of Oral Controlled Release Drug Delivery SRP, 1 (2), 128-132. doi:10.4103/0975-8453.75054 Turabian Style Patel RR, Patel JK. 2010. Technologies of Oral Controlled Release Drug Delivery Systematic Reviews in Pharmacy, 1 (2), 128-132. doi:10.4103/0975-8453.75054 Chicago Style Patel RR, Patel JK. Novel Technologies of Oral Controlled Release Drug Delivery System. Systematic Reviews in Pharmacy 1 (2010), 128-132. doi:10.4103/0975-8453.75054 MLA (The Modern Language Association) Style Patel RR, Patel JK. Novel Technologies of Oral Controlled Release Drug Delivery System. Systematic Reviews in Pharmacy 1.2 (2010), 128-132. Print. doi:10.4103/0975-8453.75054 APA (American Psychological Association) Style Patel RR, Patel JK (2010) Technologies of Oral Controlled Release Drug Delivery Systematic Reviews in Pharmacy, 1 (2), 128-132. doi:10.4103/0975-8453.75054

Externally Triggered Glass Transition Switch for Localized On‐Demand Drug Delivery

I want a new drug dose: External on-demand laser triggering is used in a drug-delivery concept, with on/off ratios in excess of 1000/1. The switching mechanism involves the glass transition of hydrophobic polymers with a large change in diffusivity. Formation of a glassy surface layer of the implant in the off state plays a key role, resulting in negligible off-release. (Picture: data points indicate ibuprofen concentration).

Organic–Inorganic Composites for Bone Drug Delivery

This review paper attempts to provide an overview in the fabrication and application of organic-inorganic based composites in the field of local drug delivery for bone. The concept of local drug delivery exists for a few decades. However, local drug delivery in bone and specially application of composites for delivery of drugs to bone is an area for potential research interest in the recent time. The advantages attained by an organic-inorganic composite when compared to its individual components include their ability to release drug, adopting to the natural environment and supporting local area until complete bone regeneration, which make them carriers of interest for local drug delivery for bone.

Preparation of Polymeric Carriers for Drug Delivery with Different Shape and Size Using an Electric Jet

A method for generating poly(lactic-co-glycolic acid) and polycaprolactone biodegradable particles of different size and shape using a jet generated in an electric field is elucidated. These particles are suitable for use as drug carriers and the method can be developed into a mass production route. The effect of different parameters such as applied voltage, collecting distance, flow rate and polymer concentration on inducing size and shape differences in these particles was studied. It was found that the flow rate, polymer concentration and collecting distance have a significant impact on the size of the generated particles and by changing the collecting distance a systematic reduction in the particle size by at least an order of magnitude (10microm-100nm) can be achieved. By using a high polymer concentration (30 wt. %) the shape and surface morphology of these particles can also be controlled from spherical to fibrous, and smooth to irregular, respectively, which presently is an interesting strategy and concept in drug delivery. This method is very useful as a one-step generator of different sizes of drug carriers with morphological variations.

Molecular Dynamics of PEG−Dendrimer Blends and PEGylated Dendrimers

Molecular dynamics of a series of poly(ethylene glycol)−poly(amidoamine) (PEG−PAMAM) dendrimer blends and PEG conjugated PAMAM dendrimers were investigated and contrasted using broadband dielectric relaxation spectroscopy (DRS). The study was carried with 2000 Da PEG and generation 3 PAMAM dendrimers. The results were generated over a wide range of frequencies and temperatures. A number of relaxation processes were detected and their origin and characteristics established. PEG−dendrimer blends show three local processes and a segmental process contributed by the amorphous PEG. The time scale of segmental relaxation decreases with increasing concentration of dendrimers due to the H-bonding that forms between the PEG oxygen and the amino groups on the surface of dendrimers. PEGylated dendrimers show two local processes and a segmental process, also contributed by the amorphous PEG. But unlike the blends, the amorphous PEG in PEGylated dendrimers is constrained not only by the crystalline lamellae but also by the covalent bonds with the dendrimer. This results in a different morphology which, in turn, gives rise to a different time scale of segmental relaxation in PEG−dendrimer blends and PEGylated dendrimers. A comprehensive analysis of the effect of morphology, concentration of dendrimers, number of attached PEG chains, and temperature on the relaxation time, dielectric relaxation strength, and spectral characteristics of various relaxation processes is offered. The results reported here are expected to provide an added dimension to our understanding of the principles that guide drug delivery concepts.

Transdermal Drug Delivery System: Patent Reviews

Transdermal drug delivery represents one of the most rapidly advancing areas of novel drug delivery. Although the concept of transdermal drug delivery has been known since 1924, it took until 1979, as FDA approved the transdermal delivery of scopolamine, that transdermal delivery systems [TDDS] received broad attention as novel tool for controlled release. These drug delivery systems are designed for controlled release of drug through the skin into systemic circulation maintaining consistent efficacy and reducing dose of the drug and its related side effects. More than 200 patents have been granted by the United State patent alone, of which more than 35 TDD products have now been approved for sale in the US, and approximately 16 active ingredients have been approved for use globally. Statistics reveal a market of $ 12.7 billion in the year 2005 which is expected to increase by $ 21.5 billion in the year 2010 and $ 31.5 billion in the year 2015. Almost all major and minor pharmaceutical companies are developing TDDS. There is not a single review article which describes patents on different types of TDDS. Thus this review is designed for patents on the different type of TDDS which would be helpful for the researcher in the field of TDDS.

Different Concepts of Drug Delivery in Disease Entities

This is a review of classical and novel concepts of drug delivery in particular diseases such as central nervous system disease, ophthalmic disease, cardiovascular disease, cancer and others. Nowadays, scientists are trying to propose efficient and selective drugs for the site of action, with best acceptance of patients, that can be metabolized to non-toxic derivatives. Prodrugs, soft drugs, codrugs are designed to maximize the amount of active drugs that reaches the site of action, through changing the physicochemical, biopharmaceutical or pharmacokinetic properties of the parent drugs. For last years different concepts of drug delivery have been developed to achieve the best patients' tolerance of a drug that has no undesirable properties. It is established that future studies will ameliorate drug properties so as to achieve the best drug delivery system.

Optimizing Microneedle Arrays to Increase Skin Permeability for Transdermal Drug Delivery

Improving drug permeability in the skin is one of the most important issues for designing new methods of transdermal drug delivery. Consequently, many techniques have been proposed to effectively deliver drugs across the stratum corneum. The microneedle is a new technology to enhance transdermal delivery of high-molecular-weight drugs. This technique combines the concepts of transdermal drug delivery across the skin with patches and hypodermic injections. The microneedles have been shown experimentally to increase the skin permeability by orders of magnitude in vitro for a range of drugs that differ in molecular size and weight. Recently, other questions appeared while using these microneedles, such as how to reduce needle diameters by which the hole is produced to be as small as possible to exclude bacteria and other foreign particles. Another issue is how to correlate the skin thickness and microneedle length with the skin permeability. In this work, we have developed an optimization framework for improving skin permeability to drugs by using microneedle arrays, which considers different classifications of skin thickness arising from different races, sex groups, ages, and anatomical regions. To know the optimum design of these microneedles, the effect of the microneedle geometry (e.g., number of microneedles, microneedle radius) on skin should be determined. In this work, the optimization algorithm is presented. The outcome of this work will be used to suggest optimum microneedle designs based on the parameters of interest.

Release and Molecular Transport of Cationic and Anionic Fluorescent Molecules in Mesoporous Silica Spheres

We describe here a method for study of bulk release and local molecular transport within mesoporous silica spheres. We have analyzed the loading and release of charged fluorescent dyes from monodisperse mesoporous silica (MMS) spheres with an average pore size of 2.7 nm. Two different fluorescent dyes, one cationic and one anionic, have been loaded into the negatively charged porous material and both the bulk release and the local molecular transport within the MMS spheres have been quantified by confocal laser scanning microscopy. Analysis of the time-dependent release and the concentration profiles of the anionic dye within the spheres show that the spheres are homogeneous and that the release of this nonadsorbing dye follows a simple diffusion-driven process. The concentration of the cationic dye varies radially within the MMS spheres after loading; there is a significantly higher concentration of the dye close to the surface of the spheres (forming a "skin") compared to that at the core. The release of the cationic dye is controlled by diffusion after an initial period of rapid release. The transport of the cationic dye within the MMS spheres of the dye from the core to near the surface is significantly faster compared to the transport within the surface "skin". A significant fraction of the cationic dye remains permanently attached to the negatively charged walls of the MMS spheres, preferentially near the surface of the spheres. Relating bulk release to the local molecular transport within the porous materials provides an important step toward the design of new concepts in controlled drug delivery and chromatography.

Encapsulation and release of plasminogen activator from biodegradable magnetic microcarriers

There are a number of therapies available to recanalize occluded arteries. However, even though proven beneficial, these approaches are not without significant shortcomings. Previous research showed that by encapsulating therapeutic thrombolytic enzymes in liposomic formulations, the reperfusion times in vivo were significantly lower than for administration of free thrombolytic. Like liposomes, biodegradable, diblock polymers of poly(lactic acid)–poly(ethylene glycol) (PLA–PEG) have been shown to have therapeutic benefit as delivery vehicles for a variety of drug delivery concepts. We report on new formulations based on tissue plasminogen activator (tPA) encapsulated in magnetic, PLA–PEG microcarriers. We studied the tPA encapsulation efficiency, loading, and release after varying the molecular weight of polymer, carrier size, tPA solution composition, and use of ultrasound to enhance release. We loaded 3.3–9.4 wt% tPA and 12–17 wt% magnetite into the carriers, depending on the exact formulation. The release of tPA was complete 20 min after reconstitution. Ultrasound insonation failed to enhance tPA release rates in smaller carriers but significantly enhanced release in larger carriers. With these formulations, we should be able to achieve lytic concentrations if we can magnetically concentrate 5 mg of carrier within about 11 ml of blood volume near the clot.