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Arteriosclerosis, Thrombosis, and... Jun 2001We present the first steps in the elaboration of an approach of extracellular matrix-targeted local drug delivery (ECM-LDD), designed to provide a high concentration,...
We present the first steps in the elaboration of an approach of extracellular matrix-targeted local drug delivery (ECM-LDD), designed to provide a high concentration, ubiquitous distribution, and long-term retention of a drug within the vessel wall after local intravascular delivery. The approach is based on the concept of a bifunctional drug comprising a "therapeutic effector" and an "affinity vehicle," which should bind to an abundant component of the vessel wall. The aim of the present study was to select molecules suitable for the role of affinity vehicles for ECM-LDD and to study their intravascular delivery and retention ex vivo and in an animal model. By use of fluorescence microscopy, the following molecules were selected on the basis of strong binding to cross sections of human vessels: protamine, polylysine, polyarginine, a glycosaminoglycan-binding peptide from vitronectin, and a synthetic dendrimer. With polylysine as a prototypic affinity vehicle, we showed that after intravascular delivery, polylysine was concentrated throughout a luminal layer of the vascular wall to an extremely high concentration of 20 g/L and was retained therein for at least 72 hours of perfusion without noticeable losses. Low molecular weight (fluorescein) and high molecular weight (hirudin) compounds could be chemically conjugated to polylysine and were retained in the vessel wall after intravascular delivery of the conjugates. In conclusion, by use of the ECM-LDD method, an extremely high concentration and long-term retention of locally delivered drug can be reached. Polycationic molecules can be considered as potential affinity vehicles for ECM-LDD.
Topics: Animals; Aorta; Arterial Occlusive Diseases; Arteries; Carotid Arteries; Culture Techniques; Drug Delivery Systems; Extracellular Matrix; Glycosaminoglycans; Hirudins; Humans; Male; Microscopy, Fluorescence; Peptides; Pharmaceutical Vehicles; Polylysine; Protamines; Rats; Rats, Wistar; Umbilical Arteries
PubMed: 11397701
DOI: 10.1161/01.atv.21.6.943 -
Acta Pharmaceutica Suecica 1983
Topics: Administration, Topical; Biological Transport; Dose-Response Relationship, Drug; Estradiol; Glycols; Humans; In Vitro Techniques; Metronidazole; Pharmaceutical Vehicles; Regression Analysis; Skin Absorption
PubMed: 6675422
DOI: No ID Found -
Archives of Ophthalmology (Chicago,... Jan 1975Radioactive sodium pentechnetate Tc 99m was added to commonly used ophthalmic drug vehicles of saline, 1% methyicellulose, 1.4% polyvinyl alcohol, and a 6:4 mixture of...
Radioactive sodium pentechnetate Tc 99m was added to commonly used ophthalmic drug vehicles of saline, 1% methyicellulose, 1.4% polyvinyl alcohol, and a 6:4 mixture of white petrolatum-mineral oil ointment. These drug vehicles containing 99m Tc were placed on both rabbit and human eyes and the rate of disappearance of the radioactivity determined. The ocular retention of 99m Tc by the eye was much longer in the nonblinking eye regardless of the vehicle used. The rate of loss of 99m Tc from the eye was fastest with saline and slowest with the ointment, with methylcellulose and polyvinyl alcohol in between. The longest contact time of the drug vehicle with the eye is afforded by the use of the ointment vehicle and the covering of both eyes.
Topics: Absorption; Administration, Topical; Adult; Animals; Eye; Female; Half-Life; Human Experimentation; Humans; Male; Methylcellulose; Middle Aged; Mydriatics; Ointments; Ophthalmic Solutions; Pharmaceutical Vehicles; Pilocarpine; Polyvinyl Alcohol; Pupil; Rabbits; Radioisotopes; Sodium; Technetium; Time Factors
PubMed: 1111487
DOI: 10.1001/archopht.1975.01010020046008 -
Journal of Drugs in Dermatology : JDD Jun 2011Many topical medications are available for the treatment of papulopustular rosacea. While treatments contain metronidazole, azelaic acid, or sodium sulfacetamide-sulfur... (Review)
Review
Many topical medications are available for the treatment of papulopustular rosacea. While treatments contain metronidazole, azelaic acid, or sodium sulfacetamide-sulfur as the active ingredient, the composition of the vehicle formulations varies widely. These vehicles come in gels, creams, lotions and foams; some ingredients are common to many vehicles, while some vehicles contain unique ingredients designed to optimize skin penetration and delivery of the active drug to its target. Vehicles can also influence tolerability, which is always a concern in patients with heightened skin sensitivity, and compliance, which is typically lower for topical treatments than oral treatments. Ideally, the vehicle of any rosacea treatment should enhance drug delivery, be nonirritating and be easy to use. Ingredients that help repair barrier function are also desirable. This review will focus on the key components of the vehicles from the most commonly used topical therapies for papulopustular rosacea and how vehicle formulations influence the delivery of active ingredient, skin barrier repair, tolerability and compliance.
Topics: Administration, Cutaneous; Dermatologic Agents; Drug Delivery Systems; Humans; Medication Adherence; Pharmaceutical Vehicles; Rosacea
PubMed: 21637903
DOI: No ID Found -
Scientific Reports 2013Searching and detecting in some harsh environments such as collapsed buildings, pipes, small cracks are crucial for human rescue and industrial detection, military...
Searching and detecting in some harsh environments such as collapsed buildings, pipes, small cracks are crucial for human rescue and industrial detection, military surveillance etc. However, the drawbacks of traditional moving modes of current vehicles make them difficult to perform such tasks. So developing some new vehicles is urgent. Here, we report a Setaria viridis spike's interesting behavior on a vibrating track, and inspired by that phenomena we develop a concept for cargo delivery, and give a detailed discussion about its working mechanism. This vehicle can move on a wide range of smooth and rough surfaces. Moreover, its climbing capability in tilted and even vertical smooth pipe is also outstanding. These features make it suitable for search-rescue, military reconnaissance, etc. Finally, this vehicle can be reduced into micro/nano-scale, which makes it would play an important role in target-drug delivery, micro-electromechanical systems (MEMS).
PubMed: 23677337
DOI: 10.1038/srep01851 -
Drug Development and Industrial Pharmacy 2015The present study is focused on optimization of elastic liposomes-in-vehicle formulations in respect to drug release and formulation properties. By combining penetration...
OBJECTIVE
The present study is focused on optimization of elastic liposomes-in-vehicle formulations in respect to drug release and formulation properties. By combining penetration potential of elastic liposomes containing high ratio of entrapped drug and physicochemical properties of vehicles, both affecting the release and texture properties, optimal formulation could be achieved.
MATERIALS AND METHODS
Deformable, propylene glycol-containing or conventional liposomes with hydrophilic model drug (diclofenac sodium) were incorporated into the following vehicles appropriate for skin application: a hydrogel, a cream base and derma membrane structure base cream (DMS base). Each formulation was assessed for in vitro drug release and mechanical properties.
RESULTS AND DISCUSSION
The composition and type of both liposomes and the vehicle affected the rate and amount of the released drug. The cream base exhibited the slowest release, followed by the hydrogel and DMS base. Similar release profiles were achieved with both types of elastic vesicles (deformable and propylene glycol liposomes); the slowest release was observed for conventional liposomes, regardless of the vehicle used. The drug release profiles from different liposomes-in-vehicle formulations were in agreement with the physicochemical properties of the formulations. All of the liposomes were found to be compatible with the hydrogel preserving its original textures, whereas a significant decrease in all texture parameters was observed for liposomes-in-DMS base, regardless of liposome type.
CONCLUSION
Propylene glycol liposomes-in-hydrogel is considered as the optimal formulation for improving skin delivery of hydrophilic drug. Further investigations involving in vivo animal studies are necessary to confirm its applicability in skin therapy.
Topics: Administration, Cutaneous; Chemistry, Pharmaceutical; Diclofenac; Drug Delivery Systems; Elasticity; Liposomes; Skin; Skin Absorption
PubMed: 25019501
DOI: 10.3109/03639045.2014.938658 -
Cutis May 2008An aqueous gel formulation containing solubilized clindamycin phosphate 1.2% and a stable combination of both solubilized and crystalline tretinoin 0.025% (clin/tret)... (Review)
Review
An aqueous gel formulation containing solubilized clindamycin phosphate 1.2% and a stable combination of both solubilized and crystalline tretinoin 0.025% (clin/tret) has been evaluated in 3 pivotal phase 3 studies, among other studies including a 52-week trial. The pivotal studies enrolled 4550 participants 12 years and older with mild, moderate, and severe acne vulgaris. The combination clin/tret gel was effective in reducing both inflammatory and noninflammatory lesions and was well-tolerated. This article reviews important vehicle characteristics of the combination gel as well as formulation stability and tolerability data that are potentially clinically relevant.
Topics: Acne Vulgaris; Administration, Cutaneous; Anti-Bacterial Agents; Benzoyl Peroxide; Clindamycin; Dermatitis, Irritant; Dermatologic Agents; Drug Combinations; Drug Interactions; Drug Stability; Gels; Humans; Pharmaceutical Vehicles; Skin Absorption; Tretinoin
PubMed: 18543590
DOI: No ID Found -
Methods and Findings in Experimental... Mar 1989The histochemical and physicochemical aspects of skin permeability and transdermal drug permeation are reviewed under preponderant consideration of the past years'... (Review)
Review
The histochemical and physicochemical aspects of skin permeability and transdermal drug permeation are reviewed under preponderant consideration of the past years' literature supplied by relevant investigations from the author's laboratories. The chemical composition and the physical order of the horny layer lipids as well as the interactions of drugs and vehicle components with these lipids are the basis of understanding drug penetration, its influencing by vehicles and penetration enhancement. By means of measuring drug concentration profiles in human skin the mechanisms of vehicle effects and penetration enhancement are demonstrated. The consequences of increased permeability and xenobiotic enrichment in pathologically altered skin are discussed.
Topics: Animals; Humans; Pharmacokinetics; Skin; Skin Absorption
PubMed: 2657274
DOI: No ID Found -
Acta Pharmaceutica Suecica 1983
Topics: Administration, Topical; Biological Transport; Estradiol; Glycols; Humans; In Vitro Techniques; Metronidazole; Pharmaceutical Vehicles; Skin Absorption
PubMed: 6675423
DOI: No ID Found -
Food and Chemical Toxicology : An... Jun 2001Accurate risk assessment in allergic contact dermatitis is dependent on the successful prospective identification of chemicals which possess the ability to behave as... (Review)
Review
Accurate risk assessment in allergic contact dermatitis is dependent on the successful prospective identification of chemicals which possess the ability to behave as skin sensitisers, followed by appropriate measurement of the relative ability to cause sensitisation; their potency. Tools for hazard identification have been available for many years; more recently, a novel approach to the quantitative assessment of potency--the derivation of EC3 values in the local lymph node assay (LLNA)--has been described. It must be recognised, however, that these evaluations of chemical sensitisers also may be affected by the vehicle matrix in which skin exposure occurs. In this article, our knowledge of this area is reviewed and potential mechanisms through which vehicle effects may occur are detailed. Using the LLNA as an example, it is demonstrated that the vehicle may have little impact on the accuracy of basic hazard identification; the data also therefore support the view that testing ingredients in specific product formulations is not warranted for hazard identification purposes. However, the effect on potency estimations is of greater significance. Although not all chemical allergens are affected similarly, for certain substances a greater than 10-fold vehicle-dependent change in potency is observed. Such data are vital for accurate risk assessment. Unfortunately, it does not at present appear possible to predict notionally the effect of the vehicle matrix on skin sensitising potency without recourse to direct testing, for example by estimation of LLNA EC3 data, which provides a valuable tool for this purpose.
Topics: Allergens; Biological Assay; Dermatitis, Allergic Contact; Hazardous Substances; Humans; Lymph Nodes; Pharmaceutical Vehicles; Risk Assessment
PubMed: 11346493
DOI: 10.1016/s0278-6915(00)00169-1