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At least 127 records · Page 7Linked to original sources
PubMed2005

Recombinant virus like particles as drug delivery system.

The drug delivery system described here is based on a virus like particle consisting of the recombinant expressed major capsid protein of Polyomavirus, VP1. Polyoma, a murine virus belonging to the Papovaviridae, forms a non-enveloped icosahedral capsid. These capsids are organized as a double shell composed of three different proteins: VP1,VP2 and VP3. The outer shell of the vision is composed of 360 VP1 molecules arranged as 72 pentamers. These capsids have a diameter of about 50 nm. The VP1 protein acts as a major ligand for certain membrane receptors during virus infection. Furthermore, the N-terminus of the VP1 protein contains a DNA-binding domain and a nuclear localization sequence. The recombinant production of the VP1 protein offers a save way to obtain a highly purified, non pathogenic pharmaceutical excipient. Combining these aspects, VP1 proteins provide a targeting as well as a drug binding site when used as a save drug carrier for gene therapy. Current applications are also including oligonucleotides as well as small molecules as well as vaccines.

Animals↗
PubMed2002

In vivo evaluation of novel hyaluronan/chitosan microparticulate delivery systems for the nasal delivery of gentamicin in rabbits.

Biodegradable microparticles containing gentamicin were prepared using chitosan hydroglutamate (CH), hyaluronic acid (HA) and a combination of both polymers by a solvent evaporation method. These formulations were administered nasally via an insufflator. Gentamicin was also administered nasally into rabbits as a solution and powder (a physical mixture of gentamicin and lactose), intravenously (IV) and intramuscularly (IM). The resultant serum levels of gentamicin were determined by Fluorescence Polarisation Immunoassay (FPIA). The bioavailability of gentamicin was poor when administered as a nasal solution (1.1%) and dry powder (2.1%) when compared with IV. However, the microparticulate systems composed of CH and HA/CH considerably enhanced the bioavailability of gentamicin (31.4 and 42.9%, respectively,) with HA microparticles inducing a less significant enhancement (23.3%). Previous in vitro dissolution and frog palate studies indicated that these microparticulate formulations were all mucoadhesive and demonstrated prolonged drug release. Such findings were translated into an increase in the bioavailability of gentamicin when compared with a simple nasal solution in vivo. When HA and CH were combined in the HA/CH formulation, the polymers appeared to improve the absorption of incorporated gentamicin synergistically in comparison to the individual polymers, suggesting a promising nasal delivery system.

Adjuvants, Pharmaceutic↗
PubMed2002

Targeting tumors with non-viral gene delivery systems.

Targeting therapeutic genes to tumors is an attractive concept in curing malignant diseases. Systemic gene delivery systems are needed for therapeutic applications in which the target cells are not directly accessible, and which can only be reached via the systemic route. Recent developments in the field of non-viral gene delivery have shown that, based on (poly)cationic carrier molecules, DNA can be efficiently targeted to tumors via the bloodstream. Tailor-made synthetic vectors can be used to achieve predominant gene expression in tumor tissue. Therapeutic concepts based, for example, on suicide genes or cytokines, showed encouraging results in preclinical and also in first clinical evaluations.

Animals↗
PubMed1978

Simulated respiratory system for in vitro evaluation of two inhalation delivery systems using selected steroids.

A simulated respiratory system was developed for the in vitro evaluation of two differently designed oral inhalation delivery systems. The deposition properties of a newly designed delivery system used for triamcinolone acetonide were compared to the more conventional, commercially available adapter utilized for an aerosol containing beclomethasone dipropionate. The simulated respiratory system was constructed so that the delivered dose of active ingredient could be classified into two fractions: the fraction that would be deposited in the oral cavity and throat and the fraction that would reach the desired site of activity in the respiratory tract. Based on this method, the newly designed system delivered more than 95% of the labeled dose to the desired site. The beclomethasone dipropionate aerosol system, which was observed to discharge the active ingredient with a greater intensity, delivered approximately 40% of the labeled dose. The particle-size distribution of the dose dispensed from the newly designed delivery system attached to the triamcinolone acetonide aerosol was determined using an impactor technique. No effort was made to correlate these results with an in vivo response.

Aerosols↗
PubMed1997

Evolution of computer-based information systems and networks to support integrated health care delivery systems.

As health care delivery systems become more integrated with an emphasis on community wellness and prevention, well-developed information infrastructures will be needed to support their activities. The article introduces several previously published independent models for the evolution of integrated delivery systems, computer-based patient records (CPRs), and health information networks as well as a summary model that illustrates the relationship among these entities and their somewhat parallel development.

Chronic Disease↗
PubMed1996

Interrelationship between buffer systems and particle sizes of TCPL drug delivery system.

The specific objective of this investigation is to study the effect of tricalcium phosphate delivery system (TCPL) particle sizes on the final density as well as the delivery profiles of various organic compounds in three different buffer environments. Each TCPL matrices were fabricated using three different particle sizes ranges between 1-38, 45-63 and 63-75 microns. The sintered microcrystal material was impregnated with either progesterone (P, 100 mg each) or bovine serum albumin (BSA, 100 mg each). In phase I of the study, each device was suspended in a serum bottle containing 100 mls of ethanol solution (50% wt/vol.) for P release or 100 mls of PBS (pH 7.4) for BSA release. In phase II, similar capsules were suspended in human plasma instead of standard buffers. The vials were agitated at 100 cycle per minute in a water bath set at 37 degrees C. The amount of P or BSA released from the devices into the buffered medium was measured spectrophotometrically. The results of this investigation revealed that a significant difference in the densities of the devices made from the range of individual particle sizes. The rate of steroid hormone and protein released from the devices made from 1-38 micron particle sizes was slower (p < 0.05) than the rate of delivery of P and BSA released from devices fabricated from either 45-63 or 63-75 micron particles. Regardless of the particle sizes effect the results show that the delivery profiles of BSA was higher than the rate of P. This observation could be attributed to the molecular structure as well as the physiochemical characteristics of the drug. In conclusion the data obtained from this study suggest that: (1) Particle sizes variations influence the density of the TCPL delivery system, (2) the rate of release of organic compounds from the ceramic devices is considerably affected by the physiochemical characteristics of medium or buffer system, and (3) the delivery rate of drugs from TCPL devices is directly proportional to the size of the device initial particles and macropores, and inversely proportional to the number of micropores within each device.

Buffers↗
PubMed2002

Synthesis and biological evaluations of brain-targeted chemical delivery systems of [Nva2]-TRH.

Various chemical delivery systems for [Nva2]-TRH were synthesized and their CNS activity was investigated and compared with that of a similar chemical delivery system of [Leu2]-TRH, previously studied. Sequential metabolism of the chemical delivery system delivered to the brain, starting with the conversion of the dihydrotrigonellyl (DHT) to the trigonellyl (T+) moiety, will provide the lock-in to the brain of the T+-chemical delivery system, which will undergo hydrolysis of the cholesteryl ester, formation of the Pr-amide and cleavage of the spacer-T+ part, allowing ultimately the sustained release of the active [Nva2]-TRH. The CNS activity was assessed by measuring the extent of antagonizing barbiturate-induced sleeping time in mice. The fully packaged DHT-Pro-Pro-Gln-Nva-Pro-Gly-OCh produced robust antagonism, reducing sleeping time from 89 min to 48 min, similar to the Leu2-analogue (49 min). However, the partially substituted [Nva2]-TRH analogues showed little or no CNS activity. The results indicate that the fully packaged delivery system is necessary to produce the successful brain targeting of the precursor construct and effective release of the Gln-Nva-ProNH2.

Amino Acids↗
PubMed1999

Diamond-shaped optical fiber delivery system.

OBJECTIVE: Physicians who use laser systems are looking for new fiberoptic delivery systems with better performance. We searched for a delivery system with high power and with a tip of high durability that may be reused many times. SUMMARY BACKGROUND DATA: The delivery systems currently found on the market can burn and break easily. The surgeon may either finish the surgery with a damaged delivery system, or have to switch to a new one during surgery, thus increasing the inconvenience and cost of the surgery. METHODS: Distal tips of fibers used with Nd:YAG and diode lasers have been shaped and polished according to their specific function, including excision, vaporization, and coagulation of tissue. RESULTS: We have developed several prototypes of optical fiber delivery systems, and in particular, we have developed a prototype of a delivery system, called the Diamond-Shaped Optical Fiber Delivery System, or Diamond. By making the tip of an optical fiber diamond shaped, we are able to obtain greater mechanical resistance than that of other delivery systems that were tested in our laboratory. In the Colorectal Unit, we applied it in surgical procedures such as perianal fistulectomy, hemorrhoidectomy, and excision of condilomata acuminata and pilonidal cyst and sinuses. During cutting and coagulating, the system performed well with no technical problems. CONCLUSIONS: A new delivery system (Diamond) gave satisfactory performance during surgical operations. Its main component, the diamond-shaped distal end, provided high durability and was reused many times, thus improving the quality of operations and reducing expenses greatly.

Biophysical Phenomena↗
PubMed1997

Enterprise networks. Strategies for integrated delivery systems.

More integrated delivery systems are making progress toward building computer networks that link all their care delivery sites so they can efficiently and economically coordinate care. A growing number of these systems are turning to intranets--private computer networks that use Internet-derived protocols and technologies--to move information that's essential to managing scare health care resources.

Computer Communication Networks↗
PubMed2006

Ultrasound guided site specific gene delivery system using adenoviral vectors and commercial ultrasound contrast agents.

We have evaluated if ultrasound imaging (US) and various commercially available contrast microbubbles can serve as a non-invasive systemically administered delivery vehicle for site-specific adenoviral-mediated gene transfer in vitro and in vivo. The contrast agents were tested for their ability to enclose and to protect an adenoviral vector carrying the GFP marker gene (Ad-GFP) into the microbubbles. We have also evaluated the ability of the innate immune system to inactivate free adenoviruses as well as unenclosed viruses adsorbed on the surface of the contrast agents and in turn the ability of the microbubbles to enclose and to protect the viral vectors from such agents. In vitro as well as in vivo, innate components of the immune system were able to serve as inactivating agents to clear free viral particles and unenclosed adenoviruses adsorbed on the microbubbles' surface. Systemic delivery of Ad-GFP enclosed into microbubbles in the tail vein of nude mice resulted in specific targeting of the GFP transgene. Both fluorescence microscopy and GFP immunohistochemistry demonstrated US guided specific transduction in the targeted cells only, with no uptake in either heart, lungs or liver using complement-pretreated Ad-GFP microbubbles. This approach enhances target specificity of US microbubble destruction as a delivery vehicle for viral-mediated gene transfer.

Adenoviridae↗
PubMed2000

Transdermal drug delivery system exposure outcomes.

Transdermal drug delivery systems are increasingly popular, yet few data exist regarding medical outcomes after exposures. Using data collected through a Regional Poison Information System, this retrospective study identified 61 cases of transdermal drug delivery system exposures reported over a recent 5-year period. Exposure routes included dermal (48 patients), oral (10 patients), combined oral and dermal (one patient), parenteral use of gel residue (one patient), and combined oral and parenteral (one patient). Forty-four exposures (72%) were managed by home telephone consultation only. Eleven of 17 patients (18%) evaluated in health care facilities were admitted, including eight (13%) to intensive care units. Hospital admission correlated statistically with clonidine and fentanyl exposures, oral exposures, and drug abuse. Clonidine exposure also correlated statistically with intensive care admission. One fatality was recorded, and all other patients recovered uneventfully. Transdermal drug delivery system exposures are infrequently reported to our regional poison information center but are associated with a significant hospital use and admission rate.

Administration, Oral↗
PubMed2003

[Experimental study on the prevention of after cataract by heparin drug delivery system].

OBJECTIVE: Heparin drug delivery system (HEP DDS) was developed and applied to the experimental animals for the prevention of after cataract. METHODS: Thirty New Zealand rabbits (30 eyes) received phacoemulsification, and were randomly divided into 3 groups: normal saline eye dripping (Group A); posterior chamber implantation of carrier drug delivery system (Group B) or HEP DDS (Group C). All eyes were examined by slit-lamp microscopy, the blood and aqueous humor heparin concentrations were measured and the wet weight of posterior capsules was weighed. RESULTS: (1) In the 12th week after the operation, the number of eyes developed posterior capsule opacification in Groups A, B, and C was 10, 10 and 4, respectively; with statistically very significant difference (chi(2) = 14.09, P = 0.001). (2) Twelve weeks after operation, the average wet weight of the posterior capsules in these 3 groups was (158 +/- 5) mg, (160 +/- 9) mg and (20 +/- 3) mg, respectively; with statistically very significant difference (F = 1 168.99, P = 0.000). (3) The average value of the aqueous humor heparin concentration in group C was (26 +/- 12) mg/L. (4) Light and electron microscopy did not revealed any active cell proliferation in the posterior capsules in Group C; the conjunctiva, cornea, iris, ciliary body and retina remained intact, without obviously toxic reaction. (5) No intraocular hemorrhage occurred during the follow-up period. CONCLUSION: The implantation of HEP DDS into the posterior chamber can raise the aqueous humor heparin concentration to a high level and remained for a long period. This procedure can effectively inhibit the occurrence of after cataract, has few toxic and side effects, and is proved to be a safe and effective procedure.

Animals↗
PubMed2002

In vitro and in vivo evaluations of dihydroquinoline- and dihydroisoquinoline-based targetor moieties for brain-specific chemical delivery systems.

Brain-targeted delivery of various drugs can be successfully achieved by chemical delivery systems (CDS) that contain a 1,4-dihydropyridine-based redox targetor moiety and undergo a sequential metabolism. However, the susceptibility of this moiety toward hydration in acidic media may limit the shelf-life of such compounds in aqueous formulation. Here, a systematic investigation of the chemical stability toward oxidation and hydration of ester and amide derivatives of 3-substituted 1,4-dihydropyridine, 1,4-dihydroquinoline, and 4-substituted 1,2-dihydroisoquinoline is reported, together with the in vitro stability and in vivo (rat) distribution of isoquinoline-based testosterone and hydrocortisone chemical delivery systems, which were selected as having the most suitable acid-resistant targetor moieties.

Animals↗
PubMedDate not supplied

The ENCEL system: a somatic cell protein delivery system.

A wide variety of somatic cells are being explored for the introduction of foreign genes with a view toward gene therapy. A prime requirement for successful gene therapy is the sustained expression, effective dosing, and systemic delivery of the therapeutic gene product. Microvascular endothelial cells offer several advantages over other cell types as a somatic cell gene delivery vehicle in that they provide direct secretion of protein into the blood stream and they are amendable to highly stable retroviral-based protein expression. Importantly, they also offer a large surface volume to size ratio in that they can be induced with angiogenic factors to form organized capillary-like structures in vitro when grown in a three dimensional culture system using collagen gels. These genetically-modified capillary endothelial cells (the ENCEL system) maintained in collagen gels can be stably transplanted and removed. The unique biological properties of microvascular capillary endothelial cells allows the ENCEL system to provide large numbers of cells in a small volume which offers the highly desired opportunity for providing a sustained and effective dose of a therapeutic protein. Alexion is currently applying its Unigraft immunotherapeutic and engineering technologies to commercialize a non-human ENCEL system acceptable for implantation into any patient.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Gastroretentive drug delivery systems.

A controlled drug delivery system with prolonged residence time in the stomach is of particular interest for drugs that i) are locally active in the stomach, ii) have an absorption window in the stomach or in the upper small intestine, iii) are unstable in the intestinal or colonic environment, or iv) exhibit low solubility at high pH values. This article gives an overview of the parameters affecting gastric emptying in humans as well as on the main concepts used to design pharmaceutical dosage forms with prolonged gastric residence times. In particular, bioadhesive, size-increasing and floating drug delivery systems are presented and their major advantages and shortcomings are discussed. Both single- and multiple-unit dosage forms are reviewed and, if available, results from in vivo trials are reported.

Adhesiveness↗
PubMed1979

Inadequate removal of methanol and formate using the sorbent based regeneration hemodialysis delivery system.

The sorbent based hemodialysis delivery system was shown to be ineffective for the treatment of methanol intoxication. Clinical and in vitro studies showed rapid saturation of the sorbent cartridge for methanol and formate adsorption. Methanol and formate clearances were four fold less than achieved with the recirculating single pass delivery system. The sorbent delivery system should not be used for methanol intoxication.

Formates↗