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Drug Design, Development and Therapy 2013The inherently toxic nature of chemotherapy drugs is essential for them to kill cancer cells but is also the source of the detrimental side effects experienced by... (Review)
Review
The inherently toxic nature of chemotherapy drugs is essential for them to kill cancer cells but is also the source of the detrimental side effects experienced by patients. One strategy to reduce these side effects is to limit the healthy tissue exposure by encapsulating the drugs in a vehicle that demonstrates a very low leak rate in circulation while simultaneously having the potential for rapid release once inside the tumor. Designing a vehicle with these two opposing properties is the major challenge in the field of drug delivery. A triggering event is required to change the vehicle from its stable circulating state to its unstable release state. A unique mechanical actuation type trigger is possible by harnessing the size changes that occur when microbubbles interact with ultrasound. These mechanical actuations can burst liposomes and cell membranes alike allowing for rapid drug release and facilitating delivery into nearby cells. The tight focusing ability of the ultrasound to just a few cubic millimeters allows for precise control over the tissue location where the microbubbles destabilize the vehicles. This allows the ultrasound to highlight the tumor tissue and cause rapid drug release from any carrier present. Different vehicle designs have been demonstrated from carrying drug on just the surface of the microbubble itself to encapsulating the microbubble along with the drug within a liposome. In the future, nanoparticles may extend the circulation half-life of these ultrasound triggerable drug-delivery vehicles by acting as nucleation sites of ultrasound-induced mechanical actuation. In addition to the drug delivery capability, the microbubble size changes can also be used to create imaging contrast agents that could allow the internal chemical environment of a tumor to be studied to help improve the diagnosis and detection of cancer. The ability to attain truly tumor-specific release from circulating drug-delivery vehicles is an exciting future prospect to reduce chemotherapy side effects while increasing drug effectiveness.
Topics: Antineoplastic Agents; Diagnostic Imaging; Humans; Microbubbles; Neoplasms; Pharmaceutical Vehicles; Ultrasonic Therapy
PubMed: 23667309
DOI: 10.2147/DDDT.S31564 -
International Journal of Pharmaceutics Sep 2014The purpose of this study was to compare the transdermal permeation of a model compound, diclofenac diethylamine, from a hydrophilic and lipophilic vehicle across in...
The purpose of this study was to compare the transdermal permeation of a model compound, diclofenac diethylamine, from a hydrophilic and lipophilic vehicle across in vitro models simulating compromised skin. Mineral oil served as a lipophilic vehicle while 10mM phosphate buffered saline served as a hydrophilic vehicle. Compromised skin was simulated by tape stripping, delipidization, or microneedle application and compared with intact skin as a control. Transepidermal water loss was measured to assess barrier function. Skin compromised with tape stripping and delipidization significantly (p<0.05) increased permeation of diclofenac diethylamine compared to intact and microneedle treated skin with phosphate buffered saline vehicle. A similar trend in permeation was observed with mineral oil as the vehicle. For both vehicles, permeation across skin increased in the same order and correlated with degree of barrier impairment as indicated by transepidermal water loss values: intact
vehicles found the same trend, with hydrophilic vehicle having greater delivery. In conclusion, phosphate buffered saline vehicle resulted in higher permeation into and across skin compared to mineral oil vehicle for all simulated models of compromised skin. Topics: Administration, Topical; Animals; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Humans; Hydrophobic and Hydrophilic Interactions; In Vitro Techniques; Male; Mineral Oil; Permeability; Pharmaceutical Vehicles; Rats, Hairless; Skin; Skin Absorption; Sodium Chloride; Solubility; Water
PubMed: 24979534
DOI: 10.1016/j.ijpharm.2014.06.050 -
Toxicology and Industrial Health May 2017This study evaluated the effects of three vehicles-ethanol (EtOH), isopropyl alcohol (IPA), and isopropyl myristate (IPM)-on stratum corneum (SC) absorption and...
This study evaluated the effects of three vehicles-ethanol (EtOH), isopropyl alcohol (IPA), and isopropyl myristate (IPM)-on stratum corneum (SC) absorption and diffusion of the [C]-model compounds benzoic acid and butenafine hydrochloride to better understand the transport pathways of chemicals passing through and resident in SC. Following application of topical formulations to human dermatomed skin for 30 min, penetration flux was observed for 24 h post dosing, using an in vitro flow-through skin diffusion system. Skin absorption and penetration was compared to the chemical-SC (intact, delipidized, or SC lipid film) binding levels. A significant vehicle effect was observed for chemical skin penetration and SC absorption. IPA resulted in the greatest levels of intact SC/SC lipid absorption, skin penetration, and total skin absorption/penetration of benzoic acid, followed by IPM and EtOH, respectively. For intact SC absorption and total skin absorption/penetration of butenafine, the vehicle that demonstrated the highest level of sorption/penetration was EtOH, followed by IPA and IPM, respectively. The percent doses of butenafine that were absorbed in SC lipid film and penetrated through skin in 24 h were greatest for IPA, followed by EtOH and IPM, respectively. The vehicle effect was consistent between intact SC absorption and total chemical skin absorption and penetration, as well as SC lipid absorption and chemical penetration through skin, suggesting intercellular transport as a main pathway of skin penetration for model chemicals. These results suggest the potential to predict vehicle effects on skin permeability with simple SC absorption assays. As decontamination was applied 30 min after chemical exposure, significant vehicle effects on chemical SC partitioning and percutaneous penetration also suggest that skin decontamination efficiency is vehicle dependent, and an effective decontamination method should act on chemical solutes in the lipid domain.
Topics: 2-Propanol; Adult; Benzoic Acid; Benzylamines; Epidermis; Ethanol; Humans; Myristates; Naphthalenes; Pharmaceutical Vehicles; Skin Absorption
PubMed: 27436841
DOI: 10.1177/0748233716656119 -
Current Pharmaceutical Design 2015Supersaturated systems have attracted interest to enhance the skin penetration because of the low cost and reduced risks of irritation with respect to other approaches.... (Review)
Review
Supersaturated systems have attracted interest to enhance the skin penetration because of the low cost and reduced risks of irritation with respect to other approaches. The mechanism is simply based on the increased drug driving force for transit out of the dosage form and penetrate the stratum corneum. Supersaturated systems can be obtained by preparation of solvent/non-solvent mixtures; or mixtures containing a skin penetrating solvent or a volatile solvent, and quenching. All methods are described to obtain solutions or semisolid preparations; meanwhile the solvent evaporation and quenching can be used in the transdermal patch production. The adopted formulative strategies can increase the drug concentration in the vehicle 5-fold the solubility and the corresponding increment of the thermodynamic activity determines a significant increase of the drug flux through the skin, according to the Fick's law. The main limitation of supersaturated systems is related to their thermodynamic instability that, leading to drug crystallization in the vehicle, affects the drug skin penetration. Among the possible strategies to avoid or retard this issue the use of polymeric materials appears the most efficacious. However, the crystallization of a drug during storage and/or application on the skin is driven by so many factors that the stability of supersaturated systems is unpredictable. This paper offers a comprehensive review of the literature with the aim to underline the "pros and cons" of the application of supersaturation in transdermal delivery in the light of the theoretical aspects.
Topics: Administration, Cutaneous; Animals; Humans; Models, Theoretical; Permeability; Pharmaceutical Preparations; Pharmaceutical Vehicles; Skin; Skin Absorption; Solvents
PubMed: 25925122
DOI: 10.2174/1381612821666150428125046 -
Journal of Drugs in Dermatology : JDD Dec 2012Topical steroid allergy (TSA), as defined by an allergy to either the steroid molecule itself or to an ingredient in the vehicle, is common in clinical practice, but it... (Review)
Review
Topical steroid allergy (TSA), as defined by an allergy to either the steroid molecule itself or to an ingredient in the vehicle, is common in clinical practice, but it is rarely diagnosed. This article elucidates the difficulties involved in clinically recognizing TSA, and also the appropriate protocols for its diagnosis and treatment.
Topics: Administration, Topical; Chemistry, Pharmaceutical; Cross Reactions; Drug Hypersensitivity; Humans; Patch Tests; Pharmaceutical Vehicles; Steroids
PubMed: 23547333
DOI: No ID Found -
Expert Opinion on Drug Delivery May 2007Drug delivery to the diseased lung is hindered by the buildup of fluid and shunting of blood flow away from the site of injury. The use of perfluorocarbon compounds... (Review)
Review
Drug delivery to the diseased lung is hindered by the buildup of fluid and shunting of blood flow away from the site of injury. The use of perfluorocarbon compounds (PFCs) as drug delivery vehicles has been proposed to overcome these obstacles. This drug delivery approach is based on the unique properties of PFCs. For example, PFCs can homogeneously fill the lung and recruit airways by replacing edematous fluid. Analogously, drugs administered with a PFC vehicle are expected to be homogeneously distributed throughout the lung. At the same time, intrapulmonary administration of the drug will achieve higher drug concentrations in the lung than conventional approaches, while reducing systemic exposure. Unfortunately, PFCs are poor solvents for typical drug molecules. To overcome this obstacle, several approaches, such as dispersions, prodrugs, solubilizing agents and (micro)emulsions, are under investigation to develop homogeneous PFC-drug mixtures suitable for intrapulmonary administration.
Topics: Administration, Inhalation; Animals; Fluorocarbons; Genetic Therapy; Humans; Lung Diseases; Pharmaceutical Preparations; Pharmaceutical Vehicles
PubMed: 17489652
DOI: 10.1517/17425247.4.3.247 -
Journal of Controlled Release :... Nov 2011The use of focused ultrasound can be an effective method to locally highlight tumor tissue and specifically trigger the activation of echogenic drug delivery vehicles in...
The use of focused ultrasound can be an effective method to locally highlight tumor tissue and specifically trigger the activation of echogenic drug delivery vehicles in an effort to reduce systemic chemotherapy side effects. Here we demonstrate a unique ultrasound triggered vehicle design and fabrication method where the payload and a perfluorocarbon gas microbubble are both encapsulated within the internal aqueous space of a liposome. This nested lipid shell geometry both stabilized the microbubble and ensured it was spatially close enough to interact with the liposome membrane at all times. The internal microbubble was shown to fragment the outer liposome membrane upon exposure to ultrasound at intensities of 1-1.5MPa. The focused ultrasound allowed the release of the internal payload to localized regions within tissue phantoms. The vehicles showed high payload loading efficiency of 16%, stability in blood of several hours, and low level macrophage recognition in vitro. High speed fluorescent videos present the first optical images of such vehicles interacting with ultrasound. This ability to open the outer membrane in small regions of deep tissue could provide a second level of spatial and temporal control beyond biochemical targeting, making these particles promising for in vivo animal studies.
Topics: Drug Delivery Systems; Drug Stability; Fluorocarbons; High-Energy Shock Waves; Lipids; Liposomes; Microbubbles; Pharmaceutical Vehicles
PubMed: 21745505
DOI: 10.1016/j.jconrel.2011.06.032 -
Journal of the American Academy of... Jul 2005Topical corticosteroids have been the mainstay of topical anti-inflammatory therapy of psoriasis and are available in different treatment strengths or doses and various... (Comparative Study)
Comparative Study Review
Topical corticosteroids have been the mainstay of topical anti-inflammatory therapy of psoriasis and are available in different treatment strengths or doses and various formulations or vehicles. Traditional formulations have included ointments, creams, and lotions. More recently, the mid-potency corticosteroid betamethasone valerate (BMV) and the ultra-high-potency corticosteroid clobetasol propionate (CP) have become available in a novel, thermolabile, low-residue foam vehicle for topical application. This review examines recent clinical studies on efficacy and safety of these two new formulations, BMV 0.12% foam (Luxiq; Connetics Corp, Palo Alto, Calif) and CP 0.05% foam (OLUX, Connetics Corp), as treatments for scalp and nonscalp psoriasis. The studies demonstrated that BMV foam and CP foam are safe and effective treatments for psoriasis affecting scalp and nonscalp regions of the body. BMV foam and CP foam were absorbed more rapidly and demonstrated greater total absorption than their respective comparison formulations, namely BMV lotion and CP solution. The foam vehicle also appears to be associated with better compliance and improvements in quality of life. The unique nature of the foam vehicle, together with the positive findings of in vitro studies suggest these new foam formulations may expand the options currently available for combination therapy.
Topics: Administration, Cutaneous; Adult; Betamethasone Valerate; Clobetasol; Cross-Over Studies; Dermatitis, Atopic; Dosage Forms; Double-Blind Method; Female; Forecasting; Humans; Hydrocortisone; Male; Multicenter Studies as Topic; Ointments; Pharmaceutical Vehicles; Psoriasis; Randomized Controlled Trials as Topic; Scalp Dermatoses; Single-Blind Method; Treatment Outcome
PubMed: 15968263
DOI: 10.1016/j.jaad.2005.04.029 -
Journal of Clinical Pharmacology 1973
Topics: Animals; Collagen; Pharmaceutical Vehicles; Pilocarpine; Pupil; Rabbits; Time Factors
PubMed: 4490006
DOI: 10.1002/j.1552-4604.1973.tb00217.x -
Drug Metabolism Reviews 1983
Review
Topics: Administration, Topical; Cell Membrane Permeability; Diffusion; Humans; Kinetics; Pharmaceutical Preparations; Pharmaceutical Vehicles; Skin Absorption; Solubility
PubMed: 6341025
DOI: 10.3109/03602538308991389