Stabilizing Liposomes with Nanoparticles

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Hello Steemians,

Today, just going through some of the research articles I found some of the new strategies to overcome the drug delivery processes which are more efficient. Thought to share some of it with you peoples. Liposomes have been used for many years as a delivery vehicle. The bio-compatible lipid membrane of these liposomes also helps them to adhere on to the bacterial surface and as it is made up of surfactant, which provide it the intrinsic property of antimicrobial activity (1). Well, many times the applicability of these liposomes get hindered because of their stability issue. As the size decreases the probability of fusing together increases, <100nm are more prone to fuse together (2).

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So, to overcome this issue several polymers based coating (something like polyethylene glycol) have been used (3). What this polymer coating will do is, it will not allow them to fuse or aggregate due to the steric hindrance (same charge). This not only prevents the non-specific interactions with each other but also prevents their interactions with the blood components which let them to stay long in blood. Regardless of having so many advantages, their use in the antimicrobial processes is still not effective. The coating which prevents the liposomes interactions among themselves also prevents the interaction with the bacterial cell membrane (4).

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So, there is need to develop such liposomes which will not fuse prior to the site of action and can also efficiently binds to the microbial membrane. Coating the liposomes with nanoparticles will help stabilize the liposomes, the small charged nanoparticles will provide the steric repulsion and don't let them fuse together (5). To make a more effective and smart drug-delivery liposome you just need to tailor the charge density over their surface. The positively charged liposomes will be binding to the negatively charged nanoparticle and can be fusing to the bacteria living in the acidic environment (6). Likewise, the negatively charged liposome will be binding to the positively charged nanoparticle and thriving the bacteria living in the neutral or basic environment (7). This change in pH provides the stimuli responsive binding and detachment of the nanoparticle which gives the antimicrobial activity to the system.

The liposomes carrying the nanoparticles still have the free sites for the attachment to the bacterial membrane in the absence of any such stimuli responsive binding and detachment. These nanoparticle stabilized liposomes still preserves the substantial fraction of their surface area for the attachment.

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The left out fractions of the liposomes surface are openly accessible for many of bacterial toxins. There are several bacterial species which produces toxins that are known for pore formation, which further leads to the release of the drug encapsulated into the liposome (8).

So, the question comes how they are prepared and in what ratio they should be used. The liposome can be prepared by mixing or sonicating lipid, organic solvent and aqueous solvent all together. The nanoparticle used to stabilize the liposome structure could be in a ratio of 1:200 (molar ratio). The absorbed nanoparticle on the surface ensures the stability and infusibility of the liposomes (6). To further characterize and study the structural integrity of the complex of nanoparticle and liposome, several techniques can be implied to study it. Charge integrity can be studied through the Dynamic Light Scattering which analyses the particle size and the surface zeta potential.

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Now to check the antimicrobial activity of nanoparticle stabalized liposomes, fusion study can be performed. Where the interaction between the liposomes and the bacterial membrane can be seen. As its a pH dependent activity, only on a certain pH the nanoparticles will be released from the liposomes and make the liposomes free to interact to the microbial membrane. Liposomes which releases the particle in acidic environment thrives bacterial species living in that environment like the pathogens present on our skin eg. Propionibacterium acne (9) and some of the gastric pathogens like Helicobacter pylori which are surviving at a physiological pH will be subjected to the liposome which loses nanoparticle at physiological pH (10).

For the purpose of topical delivery of these liposomes hydrogel is best suited. You may have remembered from one of my article, where I gave a brief description about hydrogels. In brief, hydrogels is a self assembled system where more than 90% part is water. These self assemble polymer network are well known for the biocompatibility, biodegradibility, tissue engineering and drug delivery. Being biocompatible and viscoelastic, hydrogel proves to be one of the best drug delivery bioactive molecule for topical studies. These liposomes when mixed to the hydrogel, the system become more efficient to deliver the drug more specifically and also minimize the excessive release. Other than the entrapment of liposomes these hydrogels have several other applications too. May be some other time I will share some knowledge on hydrogels.

Well, some of the research modification allows the liposomes to bypass the human immune system basically the endothilial cells and they are known as "Stealth liposomes" (11). They are also PEGylate to stabilize them and these stealth liposomes can attaches to specified targeted ligand like antibodies, antigen or vitamins. Targeted liposomes can specifically deliver to a target cell and drugs that are naturally toxic can reach to the infected tissue directly without infecting other near by cells. Many of the anticancer drugs can be delivered through the liposomes like Doxorubicin, daunorubicin. Cisplatin a pancreatic cancer drug can also be delivered through liposome. Apart from the drug delivery vehicle application liposomes are also capable of delivering several oral and dietary supplement (12).

Summary

In short, liposomes which are known to be antimicrobial active and also used as a drug delivery vehicle have the tendency to fuse among themselves and results in the payload loss. So, to overcome this issue instead of using any poymer which also hinders the binding to the bacterial membrane nanoparticles have been used. Which will provide charge and can be detached at a desired pH. Liposomes have so many advantages like increased efficacy, increased stability, non-toxic, flexible and bio-compatible. Yet they have some disadvantages too, low solubilty, short half life, leakage and fusion of the drug and manufacturing cash is also high. So guys its enough for now, will be writing ore on such topic in the near future.