Two-Week Aerosol Inhalation Study on Polyethylene Glycol (Peg) 3350 in F-344 Rats

Klonne, Dennis R.; Dodd, Darol E.; Losco, Patricia E.; Troup, Catherine M.; Tyler, T. R.

doi:10.3109/01480548908999141

Cited by 36 publications

(14 citation statements)

References 2 publications

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“…Further investigation of the nanocomplexes created a “stealth” drug formulation. This so-called “stealth” molecule has the ability to bypass the defense mechanisms of the airways, thus providing sustain release to a drug formulation [73]. Regarding aerosol gene therapy, the cationic polymers established effectiveness, based on their efficient binding to airway epithelial cells, as previously stated [34,37,43].…”

Section: Aerosol Drug Formulationmentioning

confidence: 99%

Vectors for Inhaled Gene Therapy in Lung Cancer. Application for Nano Oncology and Safety of Bio Nanotechnology

Zarogouldis

Karamanos

Porpodis

et al. 2012

IJMS

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Novel aerosol therapeutic modalities have been investigated for lung cancer. Inhaled gene therapy has presented safety and effectiveness previously in cystic fibrosis. However, safety concerns have been raised regarding the safety of non-viral vectors for inhaled gene therapy in lung cancer, and therefore small steps have been made towards this multifunctional treatment modality. During the last decade, numerous new nanocomplexes have been created and investigated as a safe gene delivery nano-vehicle. These formulations are multifunctional; they can be used as either local therapy or carrier for an effective inhaled gene therapy for lung cancer. Herein, we present current and future perspectives of nanocomplexes for inhaled gene therapy treatment in lung cancer.

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Section: Aerosol Drug Formulationmentioning

confidence: 99%

Vectors for Inhaled Gene Therapy in Lung Cancer. Application for Nano Oncology and Safety of Bio Nanotechnology

Zarogouldis

Karamanos

Porpodis

et al. 2012

IJMS

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“…The safety of PEG 3,350 Da has been proven in rats following 2-week exposure by aerosol [29]. However, there is no safety study on large PEG (> 5 kDa) delivered by inhalation.…”

Section: Discussionmentioning

confidence: 99%

PEGylation of paclitaxel largely improves its safety and anti-tumor efficacy following pulmonary delivery in a mouse model of lung carcinoma

Luo

Loira-Pastoriza

Patil

et al. 2016

Journal of Controlled Release

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The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription. AbstractPulmonary delivery offers an attractive route of administration for chemotherapeutic agents, with the advantages of high drug concentrations locally and low side effects systemically. However, fast clearance mechanisms result in short residence time of small molecule drugs in the lungs. Moreover, the local toxicity induced by antineoplastic drugs is considered a major obstacle for the clinical application of inhaled chemotherapy. In this study, we explored the utility of 6 kDa and 20 kDa polyethylene glycol-paclitaxel (PEG-PTX) conjugates to retain paclitaxel within the lungs, achieve its sustained release locally, and thereby, improve its efficacy and reduce its pulmonary toxicity. The conjugates increased the maximum tolerated dose of paclitaxel by up to 100-fold following intratracheal instillation in healthy mice. PEG-PTX conjugates induced lung inflammation. However, the inflammation was lower than that induced by an equivalent dose of the free drug and it was reversible. Conjugation of paclitaxel to both PEG sizes significantly enhanced its anti-tumor efficacy following intratracheal instillation of a single dose in a Lewis lung carcinoma model in mice. PEG-PTX 20k showed equivalent efficacy as PEG-PTX 6k delivered at a 2.5-fold higher dose, suggesting that the molecular weight of the conjugate plays a role in anti-cancer activity. PEG-PTX 20k conjugate presented a prolonged residency and a sustained paclitaxel release within the lungs. This study showed that PEGylation of paclitaxel offers a potential delivery system for inhalation with improved anti-cancer efficacy, prolonged exposure of lung-resident tumors to the antineoplastic drug and reduced local toxicity.

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“…Lung weights of both sexes were increased, and histopathology revealed some macrophage-filled alveoli. No histological lesions were found in other tissues (186).…”

Section: Experimental Studiesmentioning

confidence: 97%

“…In a shorter study administered via inhalation, rats were exposed to aerosols of polyoxyethylene (PEG 3350) at concentrations of 0, 109, 567, or 1008 mg/m 3 for 6 h/day, 5 days/week for 2 weeks (186). No effects were noted when animals were evaluated for clinical signs, ophthalmology, clinical chemistries, urinalyses, or gross pathology.…”

Section: Experimental Studiesmentioning

confidence: 99%

Synthetic Polymers: Polyesters, Polyethers, Polysulfones, and Other Polymers

Benson¹

2012

Patty's Toxicology

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Commercial use of polyester resins dates from the early twentieth century, when alkyd resins were first used in surface coatings. The polyesters are found today as fibers, films, laminating resins, molding resins, and engineering plastics. Many of the high molecular weight polyethers are used as engineering plastics, as are the polysulfides and the polysulfones. Important properties of these compounds and production data for the general categories are provided. Processing techniques vary widely and are discussed in the sections in this chapter. Although toxicity data for some of these polymers are limited, information is discussed in the sections in this chapter. In many cases, the finished polymers are associated with low toxicity. However, some chemicals within the finished products have been known to migrate from the polymers (although usually in small amounts). Further, some of the polymers described in this chapter are used in biomedical equipment, including grafts and other implants, dialysis membranes, or as vehicles for intravenous injections, and there may be toxicity associated with these uses. For specific medical applications, any risks should be weighed against benefits derived from the products. Consultation with medical professionals is necessary before deciding on whether to use particular devices. Certainly some of the highest potentials for concern associated with these polymers are for workers at manufacturing or processing sites. Workers may be exposed to volatile chemicals (e.g., monomers, flame retardants, additives) generated during processing of flammable solvents, elevated temperatures, or fires. Workers may also be exposed to dust or particulates generated in the manufacturing and processing of polyester fibers. Finally, explosion hazards might be possible where static charges are generated (e.g., during physical processing of polyester films over rollers) where flammable materials are used. Industrial hygiene concerns with these polymers depend on the type of resin. Examples of such concerns include the following: significant quantities of styrene may be released during the fabrication of unsaturated polyester resins; particulates that have biologically significant consequences when inhaled in large amounts may be generated in the manufacturing and processing of polyester fibers; processing of polyoxymethylene in a poorly ventilated space may release biologically significant amounts of formaldehyde into the adjacent atmosphere; or sulfur‐containing engineering resins may yield hydrogen sulfide or sulfur dioxide if heated to decomposition temperatures. The chemical inputs typically used to synthesize each of the polymers as well as relevant additives are discussed in the sections in this chapter. Toxicity data for most of these inputs can be found in other chapters of this edition of Patty's Industrial Hygiene and Toxicology . No specific standards are known that pertain to ordinary industrial use of the finished polymeric products. However, there may be occupational exposure limits for the chemicals used to synthesize or process these polymers. In addition, there are occupational exposure limits for dust and particles that may be applicable. There are also several examples of general protection measures that might be required such as using a continuous supply of fresh air to the workplace together with removal of processing fumes through exhaust systems is recommended. Also, processing fume condensates that are toxic or are fire hazards should be removed periodically from exhaust hoods, ductwork, and other surfaces by individuals using appropriate personal protection. Ventilation requirements must be locally determined to limit exposure to materials at their point of use. Use of proper personal protection while cleaning or handling condensates and plastic processing fumes should be observed. The polymers described in this chapter have generally little or no data on toxicity from burning. The toxicological aspects of plastic combustion products can be very complex in part because it is very difficult to simulate real‐world environments under controlled conditions. Also, depending on a variety of factors, the qualitative and quantitative nature of chemicals present in the combustion product mixtures will vary. Some factors that may contribute to toxicity of combustion products of these polymers include increase of carbon monoxide and carbon dioxide, decrease of oxygen, and the presence of irritant gases. The primary effects from fires are often asphyxia due to oxygen deficiency, poisoning from carbon monoxide, heat damage to tissues, and irritation of the respiratory tract by combustion gases. Some polymers are used in packaging (or directly in food), and clearances for direct or indirect food contact applications are listed under Title 21 of the Code of Federal Regulations, and are listed in the sections in this chapter. Other polymers have been approved for use in specific medical devices that may be implanted in the body or used in dialysis machines.

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Two-Week Aerosol Inhalation Study on Polyethylene Glycol (Peg) 3350 in F-344 Rats

Cited by 36 publications

References 2 publications

Vectors for Inhaled Gene Therapy in Lung Cancer. Application for Nano Oncology and Safety of Bio Nanotechnology

Vectors for Inhaled Gene Therapy in Lung Cancer. Application for Nano Oncology and Safety of Bio Nanotechnology

PEGylation of paclitaxel largely improves its safety and anti-tumor efficacy following pulmonary delivery in a mouse model of lung carcinoma

Synthetic Polymers: Polyesters, Polyethers, Polysulfones, and Other Polymers

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