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Posts Tagged ‘Torchilin’


Author: Tilda Barliya PhD

Category owner: Nanotechnology in drug deliveryImage

Nanotechnology is simply defined as the technology to manipulate the matter on the atomic and/or molecular scale. It is generalized to materials, devices and structures with dimensions sizes at the nanoscale of 1 to 1000 nanometers (nm) (1,2).

Nanotachnology can be applied to many fields including sensors, biomaterials for tissue engineering, and nanostructures or 3D materials for molecular imaging and drug delivery among others. In medicine, nanotechnology is essentially a multidisciplinary field of physics, organic and polymer chemistry as well as molecular biology, pharmacology and engineering. These fields team up together to design a better and most opt treatment option for a disease using “the right drug, the right vehicle and the right route of administration”. In pharmaceutical industries, a new molecular entity (NME) that demonstrates potent biological activity but poor water solubility, or a very short circulating halflife, will likely face significant development challenges or be deemed undevelopable. There is always a degree of compromise, and such tradeoffs may inevitably result in the production of less-ideal drugs. However, with the emerging trends and recent advances in nanotechnology, it has become increasingly possible to address some of the shortcomings associated with potential NMEs. By using nanoscale delivery vehicles, the pharmacological properties (e.g., solubility and circulating half-life) of such NMEs can be drastically improved, essentially leading to the discovery of optimally safe and effective drug candidates. (3,4).

This is just one example which demonstrates the degree to which nanotechnology may revolutionize the rules and possibilities of drug discovery and change the landscape of pharmaceutical industries. (5)

Nanomedicine is facing many challenges in overcoming biological barriers, arrival and accumulation at the target site, therefore advances in nanoparticle engineering, as well as advances in understanding the importance of nanoparticle characteristics such as size, shape and surface properties for biological interactions, are necessary to create new opportunities for the development of nanoparticles for therapeutic applications (6).

Compared to conventional drug delivery, the first generation nanosystems provide a number of advantages. In particular, they can enhance the therapeutic activity by prolonging drug half-life, improving solubility of hydrophobic drugs, reducing potential immunogenicity, and/or releasing drugs in a sustained or stimuli-triggered fashion. Thus, the toxic side effects of drugs can be reduced, as well as the administration frequency. In addition, nanoscale particles can passively accumulate in specific tissues (e.g., tumors) through the enhanced permeability and retention (EPR) effect. Beyond these clinically efficacious nanosystems, nanotechnology has been utilized to enable new therapies and to develop next generation nanosystems for “smart” drug delivery (such as gene theraphy).

In summary; there are several factors that need to be included for a rational nanocarrier design:

–          Protect the drug from premature degradation

–          Protect the drug from premature interaction with biological environment

–          Enhance the absorption of the drug into the selected tissue-site

–          Improve intracellular drug penetration

–          Improve and control the drug pharmacokinetics and distribution profile.

Moreover there are several other factors that need to be taken into consideration to effectively influence the clinical translation of the drug delivery system (DDS) i.e materials that are biodegradable and biocompatible, easily functionalized, exhibit high differential uptake efficiency etc.(7-9).

In the next few chapters, we will try to address some of these factors as well as some examples that succeeded in the clinical setting as well as those who failed.

References:

  1. Nanotechnology and Drug Delivery Part 1: Background and Applications Nelson A Ochekpe, Patrick O Olorunfemi and Ndidi C Ngwuluka.Tropical Journal of Pharmaceutical Research, June 2009; 8 (3): 265-274. http://www.tjpr.org/vol8_no3/2009_8_3_11_Ochekpe.pdf
  2. Davis, M. E., Chen, Z. & Shin, D. M. Nanoparticle therapeutics: an emerging treatment modality for cancer. Nature Rev. Drug Discov. 7, 771–782 (2008). http://www.nature.com/nrd/journal/v7/n9/abs/nrd2614.html
  3. Nanotechnology in Drug Delivery and Tissue Engineering: From Discovery to Applications Jinjun Shi,†,§ Alexander R. Votruba,§ Omid C. Farokhzad,†,§ and Robert Langer*,†,‡. Nano Lett. 2010, 10, 3223–3230. http://engineering.unl.edu/academicunits/chemical-engineering/research/focuslab/kidambi_lab/CHME_896_496_files/Impact%20of%20Nanotechnology%20on%20Drug%20Delivery-Langer_ACSNano’09.pdf
  4. Sengupta, S. et al. Temporal targeting of tumour cells and neovasculature with a nanoscale delivery system. Nature 436, 568–572 (2005) http://www.ncbi.nlm.nih.gov/pubmed/16049491
  5. Torchilin, V. P. Recent advances with liposomes as pharmaceutical carriers. Nature Rev. Drug Discov. 4, 145–160 (2005). http://www.chem.umass.edu/~thompson/Courses/chem697a/papers/TorchilinReviewLiposomeCarriers.pdf
  6. Decuzzi, P. et al. Size and shape effects in the biodistribution of intravascularly injected particles. J. Control. Release 141, 320–327 (2010) http://www.ncbi.nlm.nih.gov/pubmed?term=Decuzzi%2C%20P.%20et%20al.%20Size%20and%20shape%20effects%20in%20the%20biodistribution%20of%20intravascularly%20injected%20particles.%20J.%20Control.%20Release%20141%2C%20320%E2%80%93327%20(2010)
  7. Nanocarriers as an emerging platform for cancer therapy. Dan Peer1†, Jeffrey M. Karp2,3†, Seungpyo Hong4†, Omid C. Farokhzad5, Rimona Margalit6 and Robert Langer3,4*. nature nanotechnology 2007 |  vol 2 751-760. http://www.nature.com/nnano/journal/v2/n12/abs/nnano.2007.387.html
  8. Alonso, M. J. Nanomedicines for overcoming biological barriers. Biomed. Pharmacother. 58, 168–172 2004. http://www.ncbi.nlm.nih.gov/pubmed/15082339
  9. Torchilin, V. P. Recent advances with liposomes as pharmaceutical carriers. Nat. Rev. Drug Discov.4, 145–160 (2005) http://www.chem.umass.edu/~thompson/Courses/chem697a/papers/TorchilinReviewLiposomeCarriers.pdf

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