Vaginal matrices: nanofibers for contraception and prevention of HIV infection
Described are drug delivery systems incorporating electrospun fibers that comprise and deliver physicochemically diverse drug compounds. Such fibers provide significant advantages in drug agent release, such as adaptability for solid dosage delivery to mucosal tissues. This is in addition to allowing for controlled drug release. Systems and methods for large-scale electrospinning productivity are described, including novel microarchitectures allowing for variable pharmacokinetics in drug release.
1. A drug delivery composition comprising at least two drug agents comprised by electrospun polymer fibers, wherein said at least two drug agents include a drug agent that is hydrophobic and a drug agent that is hydrophilic, and wherein the electrospun polymer fibers include fibers that comprise said at least two drug agents dispersed along an axis of the fibers, and wherein the electrospun polymer fibers include fibers that comprise said at least two drug agents in the same fiber.
2. The drug delivery composition of claim 1 wherein the at least two drug agents in the same fiber are arranged in a uniaxial or coaxial configuration.
3. The drug delivery composition of claim 1 wherein the fibers are degradable.
4. The drug delivery composition of claim 1 in which said electrospun fibers comprise a said drug agent present in a range of 0.01%-70% by weight.
5. The drug delivery composition of claim 1 in which the different drug agents are released with differing kinetics upon contact of said composition with a hydrating fluid.
6. The drug delivery composition of claim 1 in which at least one of said drug agents modifies the release characteristics of at least one other drug agent from said fibers.
7. The drug delivery composition of claim 1 in which release characteristics are modified by the inclusion of an excipient in the solution from which fibers are electrospun.
8. The drug delivery composition of claim 1 wherein at least one drug agent is less than 10% crystalline particulate dispersion or less than 10% amorphous particulate dispersion.
9. The drug delivery composition of claim 1 , wherein the drug agents include an antimicrobial drug and a contraceptive agent.
10. The drug delivery composition of claim 9 , wherein the antimicrobial drug comprises an antiviral drug.
11. The drug delivery composition of claim 9 , wherein the antimicrobial drug comprises an antiretroviral drug.
12. The drug delivery composition of claim 11 wherein the antiviral drug comprises a drug selected from the group consisting of a viral entry inhibitor, a reverse-transcriptase inhibitor, and an integrase inhibitor.
13. The drug delivery composition of claim 11 wherein the antiviral drug is selected from the group consisting of miraviroc (MVC), cyanovirin-N(CV-N), tenofovir (TFV), dapivirine (DPV), etravirine (ETR), azidothymidine (AZT), acyclovir (ACV), raltegravir (RAL) and glycerol monolaurate (GML).
14. The drug delivery composition of claim 9 wherein the contraceptive agent comprises a hormonal or non-hormonal contraceptive drug.
15. The drug delivery composition of claim 9 wherein the contraceptive agent comprises levonorgestrel.
16. The drug delivery composition of claim 1 wherein the fibers further form a physical barrier to sperm penetration when contacted with the vagina.
17. The drug delivery composition of claim 1 wherein the polymer fibers comprise or are spun from a polymer selected from the group consisting of poly(lactide-co-glycolide) (PLGA), polylactic acid (PLA), poly ε-caprolactone (PCL), polyvinyl alcohol (PVA), polyethylene oxide (PEO), polyvinylpyrrolidone (PVP), poly methacrylic acid (PMAA) and ethyl cellulose (EC).
18. The drug delivery composition of claim 1 , formulated for delivery to the vaginal or rectal mucosa.
19. A method for producing the composition of claim 1 , wherein the composition comprises a contraceptive drug agent and an antimicrobial drug agent that is an antiviral agent, wherein the composition is produced by providing a quantity of at least one solution, and electrospinning the solution onto a substrate.
20. A method of making a drug delivery composition comprising electrospinning a polymer fiber comprising at least two different drug agents dispersed along an axis of the fiber, wherein said at least two drug agents include a drug agent that is hydrophobic and a drug agent that is hydrophilic.
21. The composition of claim 1 , wherein the drug agent that is hydrophobic and the drug agent that is hydrophilic differ in an aqueous solubility by at least an order of magnitude.