Particle delivery techniques

Abstract

A method is provided for in vivo or ex vivo delivery of a preparation of powdered nucleic acid molecules into vertebrate tissue for transformation of cells in the tissue using needleless injection techniques. The method can be used to deliver therapeutically relevant nucleotide sequences to cells in mammalian tissue to provide gene therapy, elicit immunity or to provide antisense or ribozyme functions. A method for providing densified processed pharmaceutical compositions is also described. The method is used to convert non-dense pharmaceutical powders or particulate formulations into densified particles optimally suited for transdermal delivery using a needleless syringe. The method is also used to optimize the density and particle size of powders and particulate formulations for subsequent transdermal delivery thereof. Densified pharmaceutical compositions formed by the present methods are also provided.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation of application Ser. No. 09 / 216,641, filed Dec. 17, 1998, now allowed, which is a continuation-in-part of International Patent Application Numbers PCT / GB97 / 01636, filed Jun. 17, 1997, and PCT / GB97 / 02478, filed Sep. 11, 1997, both designating the United States, from which applications priority is claimed pursuant to 35 U.S.C. §365(c), and which applications are incorporated herein by reference in their entirety.TECHNICAL FIELD [0002] The present invention relates generally to particle delivery methods. More particularly, the invention pertains to in vivo and ex vivo delivery of powdered nucleic acid molecules into mammalian tissue using needleless injection techniques. The invention also relates to methods for forming dense, substantially solid particles from non-dense particulate pharmaceutical compositions such as those prepared using freeze-drying or spray drying techniques. The densified compositions...

AI Technical Summary

Benefits of technology

[0025] In various aspects of the invention, the above method can be practiced in vivo to provide targeted delivery of the nucleic acid particles to a target tissue, such as delivery to the epidermis (for gene therapy applications) or to the stratum basal layer of skin (for nucleic acid immunization applications). In these aspects of the invention, particle characteristics and / or device operating parameters are selected to provide optimal tissue-specific delivery. One particular approach entails the selection of particle size, particle density and initial velocity to provide a momentum density (e.g., particle momentum divided by particle frontal area) of between about 2 and 10 kg / sec / m, and more preferably between about 4 and 7 kg / sec / m. Such control over momentum density allows for precisely controlled, tissue-selective delivery of the nucleic acid particles.

Problems solved by technology

However, despite its clear advantages, transdermal drug delivery presents a number of its own inherent logistical problems.

However, such techniques often give rise to unwanted side effects, such as skin irritation or sensitization.

Thus, the number of drugs that can be safely and effectively administered using traditional transdermal delivery methods has remained limited.

Particles larger than about 250 μm can also be delivered from the device, with the upper limitation being the point at which the size of the particles would cause untoward damage to the skin cells.

However, these systems pose the risk of delivery of replication-competent viruses.

However, data suggests that this method may permit only transient expression of genes and thus has only limited application.

The technique, however, is laborious and requires single cell manipulations.

Thus, the method is inappropriate for use on a large scale.

Such methods entail the injection of the DNA-containing solutions into tissue using conventional needles or cannulas, and are therefore not well suited for long term therapies or for field or home applications.

However, such biolistic techniques are not appropriate for use with large DNA molecules since precipitation of such molecules onto core carriers can lead to unstable configurations which will not withstand the shear forces of gene gun delivery.

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