Lipid Vesicles

The purpose of these experiments is to examine the driving force behind the movement of substances across a selective or semiperpeable plasma membrane. Experiment simulations examine substances that move passively through a semipermeable membrane, and those that require active transport. Those that move passively through the membrane will do so in these simulations by facilitated diffusion and filtration. The plasma membrane’s structure is composed in such a way that it can discriminate as to which substances can pass into the cell. This enables nutrients to enter the cell, while keeping unwanted substances out. Active

Within the epidermis is the stratum corneum which is the hardest layer for the drugs to pass through. The stratum corneum is only 20% water and is classified as a lipophilic membrane which is why a lipophilic opioid such as Remifentanil is needed to be able to pass through. Since a a drug delivered through a transdermal patch would have to move through all these layers before reaching the dermis where it would be absorbed, there is a delay from the time that the patch would be applied until enough of the drug had been concentrated to get the desired results (Nelson, 2013). For some patients, an initial dose of orally or IV opioid may be introduced into the system until such time that the transdermal patch has begun to be

Microneedling is highly effective in stimulating abnormal collagen and elastin function. The DermaPen3 penetrates between 0.25mm -2.5mm below the skins surface. This creates microscopic channels into the dermis of the skin. These tiny controlled

The nasal route has been extensively used for topical treatments in the past, for example, in the treatment of rhinitis with antihistamines. However, due to the appealing drug absorption potential of the nasal mucosa, intranasal administration for the systemic delivery of drugs has grown in popularity, allowing it to be considered as an alternative parenteral route of administration 11. The nasal mucosa consists of pseudostratified columnar epithelium that lies on top of a highly vascularised basement membrane. The columnar cell surface possesses microvilli which extensively aid systemic absorption through a greatly increased surface area 5. The highly vascularised mucosa plays a significant role in systemic absorption as blood flow, and subsequently the concentration gradient across the membrane, has a major influence in the absorption of drugs into the systemic circulation 1. These anatomical aspects, coupled with the nasal cavity’s thin and porous endothelial membrane provide an attractive option for a range of therapeutic applications 5. An example of such an application is the administration of fentanyl. Nasal delivery of fentanyl exhibits a rapid onset of action due to the advantageous nasal anatomy and provides a Tmax of approximately 7 minutes, a

In this method, the binding of the virion to host receptors triggers Clathrin-mediated endoycytosis.The virion attachment to the host receptor causes the binding of an adaptor protein to the receptorcytoplasmic tail. Adaptor proteins bind to clathrin, and the local concentration of adaptor proteins onthe inside face of the plasma membrane allows clathrin to multimerize to form Clathrin-Coated Pit(CCP). GTPase dynamin pinch off the CCP from the host membrane thereby releasing the Clathrin-Coated Vesicle (CCV). Auxilin and hsc70 release the clathrin basket. The vesicle then delivers itsviral content to early endosomes. Endosomal carrier vesicles transport contents of early endosometo late endosome that is near to nucleus. Then, late endosome fuses with lysosome.decrease in pHis due to vATPase ,which is used to pump out protons into vesicle.

Iontophoresis is one of many modalities used in Physical Therapy. The method behind Iontophoresis was first described in 1747 when two well know scientist, Galvani and Volta put together the knowledge that electricity can move different metal ions and that movements of ions can produce electricity. Over time, transdermal administration of drugs has grown and found its place in modern medicine. Two methods of transdermal administration are passive and active. Passive administration uses a non-ionized drug that passes through the semi-permeable membrane of the skin. Consequently, due to the fact that the skin is semi-permeable, only a small amount of the drug molecules penetrates the skin. In contrast to non-ionized drugs, ionized drugs do not penetrate and generally not considered suitable for transdermal application. However, when combined with an external source of energy such as a direct low-level electrical current, ionized drug are quite effective at reaching the tissue. The principle behind

Phospholipids are indispensable for the live organism. They are composed basically of fatty acids, a glycerol unit, a phosphate group and polar group comprising of hydrophilic head and two lipophilic tails, that enable them to maintain water while having a naturally high affinity to skin. These heads and tails can organize themselves into bilayers—structures similar to skin. What is more special is these Phospholipids retain their structure when applied and may, therefore, be described as a “second skin”.

The largest barrier to drug delivery in the body is the skin’s stratum corneum which is the outermost layer of the epidermis. Stratum corneum thickness varies from 10-40um and is made up of dead skin cells. The epidermis thickness varies from 50-100um and is located on top of the dermis layer which contains blood vessels and nerves.

Endosomal multivesicular bodies (MVBs) can either fuse with lysosomes for degradation of unwanted materials or work as storage for MHC class II molecules in dendritic cells. MVBs can also fuse with plasma membrane, resulting in the release of vesicles called exosomes into the extracellular environment as a carrier destined for simulations, since exosomes can be taken up by other cells via phagocytosis. Various cell types such as hematopoietic cells, mast cells and lymphocytes undergo the same mechanism in order to release exosomes. (Keller et al., 2006)

Biological membranes have typically many types of molecules other than the phospholipids. An example of the animal’s cholesterol with also helps strengthen the bilayer. Cholesterol also helps control the activity of membrane proteins, because

Ceramides are an example of a family of cellular lipids found in the cell membrane (Yasuda et al., 2001). Ceramides are synthesised at the endoplasmic reticulum from precursor compounds and are transported to the Golgi apparatus for conversion into one of several sphingolipids (Yasuda et al., 2001). The transport of such compounds is highly selective if not specific (Kumagai et al., 2005; Yasuda et al., 2001). Inhibiting transport is a useful tool in investigating the role of substrates (Yasuda et al., 2001) and makes an attractive target for biochemical manipulation of the cell (Ueno et al., 2001).

In 1960, renowned biologists Gorter and Grendel made a scientific breakthrough with their formulation of the phospholipid bilayer model, commonly referred to as the ‘fluid mosaic model’. Fifty years later, this structure remains the most valued proposed explanation of the composition of the surface membrane, and is highly regarded throughout the scientific community. Consequently, the general structure of the cell surface membrane is, at this point, considered highly understood. Cell surface membranes are thought to consist largely of amphipathic molecules (Fleischer et al, 1978) held together by weaker hydrophobic interactions and components of the membrane such as cholesterol. The term ‘amphipathic’ refers to molecules comprised of two

The need for developing an in vivo substitute for skin in order to develop and test drug delivery devices in the pharmaceutical industry is growing (Shergold, et al., 2006). Mechanical characteristics of the skin such as Young’s modulus, tensile strength and compressive strength will be determined to create a list of suitable materials for injection pad. The understanding of the mechanical behaviour of these layers is vital for drug delivery devices such as auto-injectors. The aim is to develop an injection pad for drug delivery device testing that resembles the skin in appearance and function.

Biomembranes play an essential role in regulating an extensive variety of cellular processes by providing an active two-dimensional lipid framework within which biochemical reactions can occur. The structure and dynamic lateral organization of these membranes selectively modulate the activity of membrane associa¬ted proteins, such as receptors and channels.1–3 Biomembranes are complex structures which are responsible for the entity of cytosolic organelles and cells. Besides a structural role, membrane components play a key role in communications between the extra- and intracellular environments, serving as messengers in signal transduction and recognition processes. The main constituents - lipids and proteins in biological membranes stay together predominantly by non-covalent interactions. Covalent interactions are also absent between lipids within membranes, resulting highly dynamic properties these assemblies. Lipids are amphipathic molecules that self-assemble into continuous double layer arrangement in aqueous environment, where polar head groups have tendency to interact with the water while hydrophobic moieties to self-associate via hydrophobic interactions. Although phospholipid molecular species vary greatly in eukaryotic cell membranes, they predominantly belong to four main lipid types: Phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidyl-ethanolamine (PE) and sphingomyelin (Sph). Asymmetric distribution of these components between extra-cellular

Initially developed and patented by L’Oréal in mid past 1970’s (10). Niosome entered the market of the cosmetics offering various advantages. “Niosome” introduced in 1987 (11) by Lancôme. Van Hal et al. reported that niosome encapsulated estradiol can be delivered through the stratum corneum, which is known to be a highly impermeable protective barrier (12, 18). Due to the high chemical stability of the surfactant as compared to the phospholipid and no requirement of special preparation and storage conditions is an advantage over the liposomes , which results in low manufacturing costs and reduced purity problems(13). Use of novel surfactant (bola surfactant) for making niosomes has been found effective for percutaneous drug delivery application as well as non-toxic (14). Upon the application of heat or agitation niosomes attain a closed bilayer structure (14). The inner aqueous core of the niosome could be used for delivery of the various hydrophobic and hydrophilic drugs such as NSAIDS, anti-inflammatory, anti-infective agents and other classes of drug which offers the biggest advantage of enhancing the transdermal drug delivery (15, 16, and