Dr. Amira Taman, Ph.D. 1

Research in nanotechnology is rapidly progressing the development of new modalities for early diagnosis and medical treatment beyond the cellular level of individual organelles is the goal of nanotechnology researchers. 2

 Nanotechnology is a general term refers to the techniques and methods for studying, designing, and fabricating devices at the level of atoms and molecules.  The word “nano” is derived from the Greek word meaning ‘‘dwarf’’  In dimensional scaling nano refers to

 Nanotechnology is very important to biology since many biological species have molecular structures at the nano-scale levels such as:  proteins  carbohydrates  lipids 4

 Nanopharmaceuticals have been targeted to every part of the body and can even penetrate the tight epithelial junctions of skin and endothelial interface of blood- brain barrier (BBB) (through which 98% of drugs cannot transverse), making high amount of drug available to these tissues or organ. 5

 Lymphatic filariasis (LF) is a major health problem in many countries due to less efficient filariasis elimination programs.  The deep-seated location of parasites within the complex anatomy of host lymphatic system is a barrier resulting in less bioavailability of antifilarial agents. 6

Drastic advancement in existing LF treatment protocols is expected to be achieved by reformulating antifilarial drugs using nanopharmaceutical technology. 7

Limitations associated with antifilarial agents for the treatment of LF. 8

Improve solubility, plasma half-life, overall pharmacokinetics and bioavailability of antifilarial agents. Provide lymphatic targeted DDS to target adult worm and Wolbachia endosymbionts. Reduced dosage and dose frequency Short treatment protocols promoting patient compliance to existing treatment strategies. Provide a wide array of multifunctional nanoparticles to overcome the billion fold fear of drug resistance. Reduced toxicity of antifilarials Advantages of using nano-medicine in Lymphatic Filariasis 9

 DDSs are polymeric or lipid carriers  They can effectively transport therapeutics to their target sites. Advantages 1. Achieve maximum pharmacological effects 2. Minimum adverse reaction 3. Preventing the degradation/denaturation/ inactivation of therapeutic agents. 10

 Optimal size range of nanoparticles.  Efficient uptake into the lymphatic system.  High uptake in the lymph nodes.  Ability to slow release of antifilarial agents to the parasites.  Prolong retention of drug in blood circulation to eliminate (mf).  Low toxicity to normal, healthy tissues. 11

Techniques Attaching specific ligands to the DDS. Modifying the surface characteristics. Attaching specific molecules to the DDS. 12

Carriers solid lipidLiposomes polymeric nanoparticles 13

 Liposomes are the first nanocarriers employed for the improvement of antifilarial drugs.  Liposomes have been well studied for their accumulation in lymph nodes or enhancing targeting to lymphatic system via subcutaneous route.  Antibody-sensitized liposomes or immunoliposomes (as “guided missiles”) also effectively evade mononuclear phagocytic clearance and are considered vital for boosting the bioavailability of microfilaricides. 14

 Tetracycline, doxycycline, and rifampicin are some of the antirickettsial antibiotics found effective against Wolbachia and can interrupt the symbiotic association between worm and bacteria, causing death of filarial worm.  Treatment is needed for a long duration to achieve the absolute elimination of Wolbachia, resulting in acute toxicity.  Liposomized tetracycline was found more competent than the free form of drug, reducing the treatment plan to 12 alternate days with better efficacy in contrast to 90/120 days oral administration of the free drug. 15

 Solid lipid nanoparticles (SLNs) are attractive pharmaceutical carriers formed of solid lipids that remain solid at room temperature.  These nanoparticles put forward certain additional advantages over other carriers in terms of toxicity, biocompatibility, and controlled drug-release kinetics.  SLNs to target intracellular bacteria Wolbachi. 16

 Polymeric nanoparticles are colloidal particles, ranging in size from 1 to 1000 nm.  A variety of biocompatible and biodegradable polymeric matrices are available for their preparation.  In the recent years, polymer-based DDSs had widely been used for the treatment of parasitic diseases and site-specific targeting of diagnostic agents to the lymphatic system. 17

Optimal particle size range for antifilarial drug delivery  From the previous studies, the researchers suggest nm diameter as the most favorable size range of nanocarriers for lymphatic targeting of antifilarials. 18

 Surface characteristics of nanoparticles have fundamental importance to interact with the environment  Owing to the peculiar anatomy of lymphatic system and interstitial resistance exerted by osmotic pressure that prevent particles uptake, surface modifications of polymeric nanoparticles are essential to enhance localization of antifilarials close to lymph-resident filaroids. 19

 Some ligands may prove useful for filarial treatment are Hyaluron, L-selectin, lectin, folate, dextrin.  Mannose attached to liposome surface increases lymph node uptake by threefold compared with control liposomes and is used to improve the delivery of antifilarials to lymph nodes.  Also, Wolbachia, expose mannose receptors on their surface and attract lectin-coated nanoparticles to target these bacteria. 20

 Uptake via RES can be avoided by coating of nanoparticles with hydrophilic polymers such as PEG and poloxamine.  The proposed mechanism for this is that these hydrophilic polymers result in adsorption of proteins on the surface of the nanoparticles which decrease opsonization in vivo. 21

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24 Thank you