skin 4 - emerging trends in topical medications

Question 1

drug delivery in 1950-80s

Answer 1

1950–1980: First generation drug delivery technologies:
Controlled release, sustained release, extended release.
Originated with Spansule® technology; 1952 by Smith Kline & French
- Enteric coatings
- Transdermal patches

Remarkable breadth and quality of technology developed and led to numerous clinical formulations introduced.

Question 2

drug delivery in 1980-2010

Answer 2

1980–2010: Second generation drug delivery technologies:
Modulated release, self-regulated drug delivery systems, zero order release systems
E.g. extended release depot injections

Main difficulty faced by 2G technologies are biological barriers that cannot be easily overcome by altering the physicochemical properties of DDSs

Greatly reduced success in introducing clinical formulations

Question 3

drug delivery in the future

Answer 3

~50 % of new drugs can’t be taken orally
Gives impetus to create innovative delivery platforms

Sugar-sensitive nanoparticles to release glucose for diabetes

Inhaled insulin / osmotic pumps / long acting depot injections

Implantable microchip arrays, store therapeutic doses of drug for months to years.
- Self-contained hermetically-sealed drug delivery device that can be implanted and removed in a physician’s office
- Fully programmable via wireless communications to adjust dosing by physician and/or patient.
- Clinically validated in humans delivering parathyroid hormone in osteoporosis patients

Trying to circumvent the biological barriers

Question 4

what is Liposomes

Answer 4

Lipid vesicles that enclose an aqueous volume
- lipid molecules form concentric bimolecular layers
- usually formed from phospholipids and possibly cholesterol
- diameters range from tens of nm to tens of m
- can trap hydrophilic materials in aqueous core, or lipophilic materials within the membrane

Question 5

what is liposomes used for?

Answer 5

Used commercially for cancers by iv infusion
amBisome (Amphotericin B in liposomes)
DaunoXome, Caelyx (daunorubicin, doxorubicin in liposomes, PEGylated liposomes)

Pilosebacceous units have been targeted using liposomes
- treat acne, alopecias, some cancers, and for systemic delivery
- tretinoin for acne, steroids for eczema, anaesthetics all shown to work in liposomal formulations

On bulk of skin, liposomes adsorb and fuse with surface
- increases the thermodynamic activity (driving force) of the drug, causes enhanced permeation of lipophilic drugs.
- Cannot work for proteins / peptides on intact skin (stratum corneum barrier remains)

Some formulations may penetrate into the stratum corneum to some extent, then fuse and release their payload
- increases drug content in the tissue
- provides a reservoir effect
- could work for macromolecules?

Generally, accepted not to traverse intact through skin

Question 6

what is iontophoresis

Answer 6

Electrical charge to repel ionic molecules
Eg +ve cation repelled by +ve cathode

Drives molecule into skin

Also get convective flow of water

Can carry neutral molecules into skin

Also tried to extract ions + glucose from skin as biomarker e.g. diabetes

Question 7

what was Iontophoresis used for and what is it used for now?

Answer 7

Greek physician Ethicus applied electric fish to treat gout

now used for:
NHS approved for hyperhidrosis (excessive sweating)
but expensive

Question 8

what is microneedles ?

Answer 8

Microneedles penetrate the SC but not to the pain receptors
Typically 100-150 m long
Can be hollow or solid
Resistance to fluid flow through fine bore
Tip of solid needles coated with drug

delivery to dermis , or both epidermis and dermis

Question 9

what can microneedle be used for in the future?

Answer 9

Can be manufactured from various materials
Silicon, polymers, carbon

Potential uses include:
Delivery of large proteins, antibodies and hormones.
Delivery of vaccines, both conventional and DNA-based.
Fluid sensing of glucose, hormones, blood gases, and therapeutic drug levels
Arrays of hollow needles could be used to continuously carry drugs into the body using simple diffusion or a pump system;
Very small microneedles could provide highly targeted drug administration to individual cells.

Awaiting regulatory approval and commercial scale up

Question 10

how is microneedles used to diagnose skin disease

Answer 10

We coated microneedles with various capture antibodies
can collect multiple disease specific antigens

Antigen presence can be detected by simply blotting onto treated papers, so can be easily used in primary care settings to aid diagnosis.
Cancers, skin sensitivity

Question 11

what is Epidermolysis bullosa

Answer 11

Epidermolysis bullosa: genetic mutations prevent normal epidermal resistance or anchoring, making the skin fragile.
Mutations in the gene laminin β3 (LAMB3), which encodes an epidermal anchoring protein

Mechanical stress and minor trauma provoke epidermal fragmentation or detachment from the dermis, causing skin blistering and ulcers.

Chronic, painful and untreatable wounds, and ultimately leads to skin cancers, infection and sometimes death. There is currently no cure.