Melt processed viral nanoparticle constructs
A melt processed viral nanoparticle construct for delivery of virus or virus-like particles to a site of interest includes a degradable polymer matrix and a plurality of virus or virus-like particles encapsulated within the degradable polymer matrix. The nanoparticle construct upon administration to the site of interest providing a sustained release of the virus or virus-like particles and/or nanoparticles upon degradation of the polymer matrix.
1. A melt processed degradable viral nanoparticle construct for delivery of virus or virus-like particles to a cell or tissue of interest of a subject, the nanoparticle construct comprising:
a biodegradable polymer matrix, and
a plurality of virus or virus-like particles encapsulated within the biodegradable polymer matrix, the nanoparticle construct upon administration to a subject providing a sustained release of the virus or virus-like particles to the cell or tissue, the virus or virus-like particles upon release from the biodegradable polymer matrix having the same or substantially similar structural and/or biochemical characteristics as the virus or virus-like particles prior to melt processing.
2. The nanoparticle construct of claim 1 , wherein the biodegradable polymer matrix includes a melt processable biodegradable polymer material that is cytocompatible and, upon degradation, produces substantially non-toxic products.
3. The nanoparticle construct of claim 2 , the virus or virus-like particles having a release profile from the biodegradable polymer material at least partially defined by the degradation of the biodegradable polymer material under physiological conditions.
4. The nanoparticle construct of claim 2 , wherein the melt processing of biodegradable polymer material and the virus or virus-like particles is at a Peclet number of about 5 to about 25, wherein the Peclet number is determined by the following equation:
Pe
=
6
πη
γ
.
R
3
k
b
T
where: η=viscosity of the polymer melt (Pa·s)
{dot over (γ)}=shear rate applied to the system (s −1 )
R=weight average radius of the particles before shear application (m)
k b =Boltzmann's constant (J·K −1 )
T=temperature of the system (K).
5. The nanoparticle construct of claim 1 , wherein the virus or virus-like particles are substantially uniformly dispersed in the biodegradable polymer matrix.
6. The nanoparticle construct of claim 2 , wherein the biodegradable polymer material has a melt temperature or a glass transition temperature below the degradation temperature of the virus or virus-like particles.
7. The nanoparticle construct of claim 2 , wherein the biodegradable polymer material comprises poly(lactic-co-glycolic acid) (PLGA) or a copolymer thereof.
8. The nanoparticle construct of claim 1 , further comprising at least one porogen.
9. The nanoparticle construct of claim 8 , wherein the porogen includes polyethylene glycol.
10. The nanoparticle construct of claim 1 , wherein the virus or virus-like particle is a bacteriophage or plant virus or virus-like particle.
11. The nanoparticle construct of claim 10 , wherein the virus or virus-like particle is a plant picornavirus or a filamentous plant virus or virus-like particle.
12. The nanoparticle construct of claim 10 , wherein the plant virus or virus-like particle is of the Secoviridae genus or Alphaflexiviridae family.
13. The nanoparticle construct of claim 10 , wherein the virus or virus-like particle is a Qβ bacteriophage or virus-like particle, cowpea mosaic virus or virus-like particle or potato virus X virus or virus-like particle.
14. The nanoparticle construct of claim 10 , wherein the plant virus or virus-like particle is a rod-shaped virus or virus-like particle.
15. The nanoparticle construct of claim 14 , wherein the rod-shaped virus is a tobacco mosaic virus or virus-like particle.
16. The nanoparticle construct of claim 1 , wherein the virus or virus-like particle is loaded with or bonded to a cargo molecule or bioactive agent.
17. The nanoparticle construct of claim 16 , wherein the cargo molecule or bioactive agent comprises at least one of a therapeutic agent, detectable moiety, or targeting agent.
18. The nanoparticle construct of claim 17 , wherein the therapeutic agent comprises an antiinfective agent, antiviral agent, anticancer agent or vaccine agent.
19. The nanoparticle construct of claim 17 , providing in situ delivery of the virus or virus-like particles upon administration to the subject.
20. The nanoparticle construct of claim 17 , being provided in the shape of a plurality of microparticles or microneedles.