Determinants of drug and polypeptide bioavailability from aerosols delivered to the lung

Byron, Peter R.

doi:10.1016/0169-409x(90)90010-p

Cited by 63 publications

(23 citation statements)

References 49 publications

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“…A wide range of other proteins and peptides for systemic delivery via the lungs are being investigated, including calcitonin, growth hormone, immunoglobulins, and granulocyte colony-stimulating factor (G-CSF) to name a few (Table 1) The advantages of this route for macromolecular delivery are well documented and recently reviewed [7,28,5,29,30], with the molecular weight of a given macromolecular drug candidate impacting significantly on the rate of absorption [31,32] and metabolism [7,5]. Despite its perceived potential, progress to market in the area of systemic delivery of proteins has been slow to-date due to a number of confounding factors including rapid clearance, instability [33], risks of immunogenicity [33] and longterm toxicity, dosing issues [28] and limited additives licensed for inhalation. These issues have been covered in some detail in recent reviews [29,30].…”

Section: Drug Candidates For Systemic Delivery Via the Lungsmentioning

confidence: 99%

In vivo animal models for drug delivery across the lung mucosal barrier☆

Cryan

Sivadas

García-Contreras

2007

Advanced Drug Delivery Reviews

130

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Section: Drug Candidates For Systemic Delivery Via the Lungsmentioning

confidence: 99%

In vivo animal models for drug delivery across the lung mucosal barrier☆

Cryan

Sivadas

García-Contreras

2007

Advanced Drug Delivery Reviews

130

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“…Besides, the lung could offer large absorptive surface area in the range of 35-140 m 2 , and thin (0.2 µm) and highly vascularized epithelium, which could lead to high bioavailability (Shoyele and Cawthorne, 2006). Moreover, inhalation is well accepted by the general population because of the convenience and good compliance (Byron, 1990). …”

Section: Introductionmentioning

confidence: 99%

Preparation of honokiol-loaded chitosan microparticles via spray-drying method intended for pulmonary delivery

Guo

Zheng

et al. 2009

Drug Delivery

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R E S E A R C H A R T I C L EPreparation of honokiol-loaded chitosan microparticles via spray-drying method intended for pulmonary delivery IntroductionAt present, many drugs in clinic have to be administered by injection because of its poor oral bioavailability. However, injection route is not convenient for the patients due to poor compliance, pain, and etc. In the search for needle-free delivery, the administration of therapeutic drugs by inhalation is a promising alternative that has gained considerable interest over the past few years (Smith, 1997;Bosquillon et al., 2004). The lung was an attractive route for drug delivery because it was an efficient portal to the bloodstream, and it also could be the target organ. Besides, the lung could offer large absorptive surface area in the range of 35-140 m 2 , and thin (0.2 µm) and highly vascularized epithelium, which could lead to high bioavailability (Shoyele and Cawthorne, 2006). Moreover, inhalation is well accepted by the general population because of the convenience and good compliance (Byron, 1990).Preparation of dry powder formulations for inhalation is an attractive and appreciated proposal because solubility and stability issues of drugs can be resolved. Furthermore, a dry powder aerosol offers the capacity to provide a wide range of single dose per inhalation. The success of inhaled particles mostly depends on their size and density, and especially aerodynamic diameter (d ae ) (Grenha et al., 2005). Generally, the powder with aerodynamic diameter ranging from 1-5 µm could guarantee a maximum deposition in the deep lung. Particles size smaller than 1 µm failed to deposit in lung because it was easily breathed out again, and particle sizes larger than 5 µm also failed to deposit in the lung because they could not pass through the upper airways and cannot reach the deep lung (Broadhead et al.,1992;Bosquillon et al., 2001).Micronization is usually adopted to reduce the particle size of powder to less than 5 µm. Traditional method of micronization was using a ball or jet mill to produce powder. Whereas milling is a destructive Abstract It has been demonstrated that spray-drying is a powerful method to prepare dry powders for pulmonary delivery. This paper prepared dispersible dry powders based on chitosan and mannitol containing honokiol nanoparticles as model drug. The results showed that the prepared microparticles are almost spherical and have appropriate aerodynamic properties for pulmonary delivery (aerodynamic diameters was between 2.8-3.3 μm and tapped density ranging from 0.14-0. 18 g/cm 3 ). Moreover, surface morphology and aerodynamic properties of the powders were strongly affected by the content of mannitol. Fourier transform infra-red (FTIR) spectrum of powders indicated that the honokiol nanoparticles were successfully incorporated into microparticles. In vitro drug release profile was also observed. The content of mannitol in powders significantly influenced the release rate of honokiol from matrices. Keywords: Honokiol nanoparticles; spray-d...

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“…Particles that are too small (< 1 µm) are exhaled and larger particles (> 5 µm) are deposited in the upper airways. 13 Initial problems related to delivery of large doses of insulin to the alveoli have been overcome by modern inhaler devices. These devices are small and can deliver insulin molecules (between 3 to 5 µm in diameter) that are capable of reaching the lung periphery.…”

Section: Inhaled Route Of Insulin Deliverymentioning

confidence: 99%

Inhaled insulin (Exubera®): combining efficacy and convenience

Bellary

Barnett

2006

Diabetes and Vascular Disease Research

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The pulmonary route, due to its rich vascularity, large surface area and immunotolerant characteristics, may be an ideal target for drug delivery. Although the inhaled route has been used to deliver drugs used in the management of respiratory disorders, success with peptide delivery has been limited by poor bioavailability. Recent advances in technology have overcome these barriers and have enabled new delivery devices to be developed. Insulin is the first peptide to be delivered successfully by this route and the first of the inhaled insulin delivery devices (Exubera ® ) has now been approved for clinical use. In clinical trials it has been shown to be effective, apparently safe and a preferred alternative to subcutaneously injected meal-time insulin. This new technology offers great convenience to patients needing insulin treatment. While it will considerably reduce the number of injections needed by people with type 1 and type 2 diabetes, it should also encourage more patients to start insulin treatment earlier. The potential benefits from improved adherence and better glycaemic control with this insulin are also significant. 2006;3:179-85 Diabetes Vasc Dis Res

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Determinants of drug and polypeptide bioavailability from aerosols delivered to the lung

Cited by 63 publications

References 49 publications

In vivo animal models for drug delivery across the lung mucosal barrier☆

In vivo animal models for drug delivery across the lung mucosal barrier☆

Preparation of honokiol-loaded chitosan microparticles via spray-drying method intended for pulmonary delivery

Inhaled insulin (Exubera®): combining efficacy and convenience

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