THE CHALLENGE
ALONG
THE TRAIL—

Enhancing
Drug Penetration
Through the
Mucus Barrier

The body is surrounded by boundary tissues that
prevent foreign matter
from penetrating.

The mucus that coats these tissues—the eyes, lung, cervical/vaginal tract, and gastrointestinal tract—serves as a protective barrier to trap and eliminate particulate matter, such as viruses, bacteria, and allergens, before these agents can enter the underlying tissues and cause infections or elicit reactions. However, in playing this pivotal role of protection, mucus may also hinder medical treatments by limiting the penetration of medications to mucus-protected tissues, thereby reducing their therapeutic effect.

 


The challenge is: can you get through mucus?
This is true in any disease where mucus can prevent you from getting to the right target. The lung, the intestine, the vagina, the eye—all of these have significant mucosal barriers. There are a variety of companies that do what I’d call ‘bioadhesive’—they stick to mucus. But Kala is the first company I’ve seen that’s actually developed a way to get through mucus to penetrate the mucosal barrier.
—Robert Langer, ScD
    Kala co-founder and Koch Institute Professor at
    Massachusetts Institute of Technology


MUCUS CAN INTERFERE WITH
THE ABILITY

OF DRUGS TO REACH OPHTHALMIC TISSUE

The tear film protecting the eye’s surface can trap and eliminate traditional suspension eyedrops as the eyelid blinks. This process can limit the penetration of drugs to target ocular tissue when treating conditions in the front of the eye, such as dry eye disease and post-operative inflammation and pain.

crystals

Traditional suspension eye drops adhere to mucins and can be rapidly cleared through blinking

Novel technologies to circumvent this barrier are an important advance in delivering therapeutic agents to the target tissue.

We looked to nature for our inspiration... and found a potential answer: the dense, net neutral, and hydrophilic coating of viruses, which minimizes interaction within the mucosal barrier and increases transport to underlying tissue.1

crystals

...and found a potential answer: the dense, net neutral, and hydrophilic coating of viruses, which minimizes interaction within the mucosal barrier and increases transport to underlying tissue.1

AMPPLIFY™
DRUG DELIVERY
TECHNOLOGY

Video

Info Graphic

Info Graphic

AMPPLIFY™ Drug Delivery Technology is designed to enhance penetration through the mucus barrier and deliver increased concentration of drug to the target ocular tissue

AMPPLIFY™ Drug Delivery Technology has been shown to improve delivery of loteprednol etabonate compared to traditional suspension eyedrops without AMPPLIFY™

In preclinical studies, AMPPLIFY™ Drug Delivery Technology delivered increased concentrations of loteprednol etabonate (LE) to target ocular tissue

LE 0.4% formulated with AMPPLIFY™ Drug Delivery Technology achieved significantly higher ocular exposure than traditional LE suspension 0.5% in the cornea*

Graph 1

LE 0.4% and 1% formulated with AMPPLIFY™ Drug Delivery Technology achieved significantly higher ocular exposure than traditional LE suspension 0.5% in the aqueous humor*†

Graph 2

Data from an in vivo pre-clinical study in 48 male rabbits, ages 4 to 5 months. Animals were randomized to receive either LE 0.4%, with AMPPLIFY™ Drug Delivery Technology or traditional LE suspension 0.5%. Concentrations of study drugs in the aqueous humor, cornea, and conjunctiva were assayed at 5 minutes, 15 minutes, 30 minutes, 1.0, 3.0, 6.0, and 12.0 hours post-dosing.
Data from an in vivo pre-clinical study in 36 male rabbits, aged 6 months. Animals were randomized to receive either LE 1%, with AMPPLIFY™ Drug Delivery Technology or traditional LE suspension 0.5%. Concentrations of study drugs in the aqueous humor and cornea were assayed at 5 minutes, 15 minutes, 30 minutes, 1.0, 3.0, and 6.0 hours post-dosing.
References: 1. Lai SK, O'Hanlon DE, Harrold S, et al. Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus. PNAS. 2007;104(5):1482-1487. 2. Schopf L, Enlow E, Popov A, et al. Ocular pharmacokinetics of a novel loteprednol etabonate 0.4% ophthalmic formulation. Ophthalmol Ther. 2014;3(1-2):63-72. 3. Data on file, Kala Pharmaceuticals, Inc.

PAT. NO.
US 9,056,057 B2
US 9,393,213 B2
US 9,532,955 B2
US 9,737,491 B2
US 9,827,191 B2
US 10,058,511 B2
US 10,646,437 B2
US 10,688,045 B2

TITLE
Nanocrystals, compositions, and methods that aid particle transport in mucus
Nanocrystals, compositions, and methods that aid particle transport in mucus
Nanocrystals, compositions, and methods that aid particle transport in mucus
Nanocrystals, compositions, and methods that aid particle transport in mucus
Compositions and methods for ophthalmic and/or other applications
Nanocrystals, compositions, and methods that aid particle transport in mucus
Compositions and methods for ophthalmic and/or other applications
Compositions and methods for ophthalmic and/or other applications

PAT. NO.
TITLE

US 9,056,057 B2
Nanocrystals, compositions, and methods that aid particle transport in mucus

US 9,393,213 B2
Nanocrystals, compositions, and methods that aid particle transport in mucus

US 9,532,955 B2
Nanocrystals, compositions, and methods that aid particle transport in mucus

US 9,737,491 B2
Nanocrystals, compositions, and methods that aid particle transport in mucus

US 9,827,191 B2
Compositions and methods for ophthalmic and/or other applications

US 10,058,511 B2
Nanocrystals, compositions, and methods that aid particle transport in mucus

US 10,646,437 B2
Compositions and methods for ophthalmic and/or other applications

US 10,688,045 B2
Compositions and methods for ophthalmic and/or other applications

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