Plant Based Excipients – The Case of Strychnos potatorum Seed Polysaccharide Nanoparticles
- Mohammad Mansour Saleh Saif, Department of Chemistry, Faculty of Science, Ibb University, Ibb, Yemen
- Nadimpalli Siva Kumar, Department of Biochemistry, University of Hyderabad, Hydrabad
- Majeti Narasimha Vara Prasad, Department of Plant Science, University of Hyderabad, Hydrabad

This article focuses on the possible application of Strychnos potatorum seed polysaccharide nanoparticles as pharmaceutical excipient.

Biodiversity provides a variety of resouces for survival and sustenance of human kind particularly for health care. In this regard plant based excipients play a key role in formulating efficient drug delivery mechanisms. Selected examples of botanical excipients are listed below;
  • Aloe vera - Liliaceae - Gelling agent, emollient, sustained release of drug
  • Anacardium occidentale - Anacardiaceae - Suspending agent
  • Anogeissus latifolia – Myrtaceae - Ghutti gum
  • Boswellia serrata - Burseraceae - resin
  • Firmina simplex - Sterculiaceae - Chacolate tree
  • Leucaena leucocephala – Fabaceae - Mimosoidae – seed emusifying agent
  • Oscimum – Lamiaceae - seed - suspending agent
  • Senna tora - Fabaceae - Caesalpinioideae - Binding agent
  • Trigonella foenum-graecum – Fabaceae -seed gelling agent
Strychnos potatorum and Sterculia urens (Gum karaya) are two natural products of global importance that came to lime light because of traditional knowledge. This write-up deals with only Stychnos potatorum L.

Strychnos potatorum L. (Loganiaceae)
It is a common tree of medicinal importance in India. It is popularly used to purify drinking water. Past traditions in India reported the use of S. potatorum seeds for cleaning the turbid water. S. potatorum is non-toxic plant and its seeds (popularly known as cleaning nuts) have high economic importance. Its seeds are one of the most important minor forest products collected by the members of the Girijan Co-operative Corporation, Andhra Pradesh (the predominant participating tribal groups are Bagatas, Valmikis, Nookadoras, Malis, and Kutias) along with other minor forest produc. A commercial product by name “NATFLOC” a “natural polyelectrolyte” has been developed with the seeds of S. potatorum by the GCC. NATFLOC is recommended for water turbidity removal up to 3000 NTU (Nephelometric Turbidity Unit). Additionally, there are many traditional and medicinal applications of the S. potatorum, in Ayurveda, Siddha, Unani, Folk, Modern, Tibetan and Homeopathy Systems of medicine.

Strychnos potatorum Seed Polysaccharide - Applications
There is a growing interest in the use of polysaccharides due to their biocompatible, biodegradable and environmentally benign characteristics. Polysaccharides are high molecular weight polymers constituted with simple sugar monomers such as glucose, fructose, galactose and mannose. They are abundant in nature, universally found in almost all living organisms. They are present in various tissues of seeds, stems and leaves of plants, body fluids of animals, shells of crustaceans and insects. They are also found in the cell walls and extra cellular fluids of bacteria, yeast and fungi and are thus renewable reservoirs for synthesizing high performance materials. Polysaccharides have complex structures and they are the most abundant of many natural products and the source of most of the biological energy. They consist of monosaccharides linked together by O-glycosidic linkages, and diversification of their monosaccharides yields a variety of properties. Although they are made up of single type of building blocks, their enormous diversity has led to a bewildering variety of species, structures and properties all performing a large variety of functions of great significance. They can also easily undergo chemical and biochemical modification to generate novel products with unique rheological and applicative properties. They are found in abundance, widely available, inexpensive, and able to select some properties according to their monosaccharides. The interactions of some of the polysaccharides with other synthetic and biopolymers have further increased their range of applicability. The versatility in the structure and properties of the polysaccharides and their derivatives, along with their modifications find widespread applications including food cosmetics petroleum and pharmaceutical industries. Moreover polysaccharides are hydrophilic, biodegradable, non toxic, stable and safe to use, which suggests their use in targeted drug delivery systems, can profoundly affect the immune system and therefore have the potential as immunomodulators with wide clinical applications. Many of the polysaccharides have specific receptors on the cells so they can be easily taken by the cells, it was reported that hyaluronic acid (HA) was taken by HA specific receptor-mediated endocytosis, and HA was suitable for the targeted drug delivery systems via their specific receptor. Some glycoproteins are known to be suitable for the receptor-mediated drug delivery systems. It was reported that the mannosylated, fucosylated, and galactosylated liposomes showed high accumulation in the liver via each specific receptor. Polysaccharides have been successfully used as drug carriers due to their superior properties and biocompatibility. The polysaccharides can have linear, branched or cyclic structures containing residues of only one type of monosaccharides or of different types of monosaccharides. The polymers of one type of monosaccharide units are called homopolysaccharides (e.g. cellulose, starch, etc) and those containing different monosaccharide units are known as heteropolysaccharides (e.g., glucomannans: polymers of glucose and mannose, galactomannans: polymers of galactose and mannose sugars, Cyclodextrins(CD) are cyclic polysaccharide with six or more glucose units arranged on a doughnut shaped ring. Depending on their structure, monomer composition and conformations, polysaccharides show different physical and chemical properties. Although large varieties of polysaccharides have a multitude of industrial uses, in many cases they need to be further modified to improve their applicability across the wide spectrum of end-uses. In the last few decades, wide ranges of chemical derivatives of these polysaccharides were developed. The chemical modifications improved the rheological properties of their solutions and hydrogels, while still maintaining their biodegradability and biocompatibility. Storage polysaccharides in seeds are mostly starches or galactomannans, in which the mannan back bone is built of ß (l?4) linked mannose residues and single unit galactose side chains are attached a (l?6) to all or some of the mannose residues.. The extent and pattern of galactosidation on the mannan backbone varies among plant varieties .

Nanoparticles
The term nanoparticle is a collective name for any colloidal carrier of submicrometer dimension and includes nanospheres, nanocapsules, and liposome. Nanotechnology is gaining considerable momentum in the Pharma domain.

The delivering of a pharmaceutically active molecule to a specific site in the body was adream and it has been a long-held aspiration with beginnings that may be traced back to Paul Erhlich, who in the early 20th century coined the phrase “magic bullet” to describe such an entity. Drug delivery systems (DDSs) can improve several crucial properties of ‘‘free’’ drugs, such as solubility, in vivo stability, pharmacokinetics, and biodistribution, enhancing their efficacy. The extensive pharmaceutical research today has led to the development of drug delivery systems and strategies, which go some way to fulfilling this idea, but few which could be described as “magic bullets.” Side-effects and toxicities still afflict these approaches and, hence, Erhlich’s visionary thinking has not yet been fully realized. This is especially relevant in tumour chemotherapy, where selective delivery to neoplastic cells in comparison to surrounding normal cells is an important principle.

There are many challenges to be faced while delivering the drug from the point of administration to the specific intended destination site in the body, in site-specific delivery of drugs is immense due to the numerous obstacles barricading the drug along its desired route. Cellular structures and indeed the very components of the cell itself will either prevent or act in some selective manner to hinder to the migration of drug from its point of administration to the intended destination site. It is obvious that modern medicine still faces many challenges, till today as we are moving forward into the 21st century. Nanotechnology is the area of research that may offer scientific advances in the future, which could lead to significant progress in the improvement of therapeutic outcomes. Instead of relying on the physicochemical properties of the drug to dictate its biodistribution, the drug is incorporated as a payload into a particle resulting in a different transit mechanism for the drug after administration. In particular, the development of nanoparticulate drug delivery systems may enhance the probability of getting a drug to its target site.The nanoparticle should have flexible nature and several properties which are incorporated onto the particle, mostly by covalent bonding to surface groups. A targeting system, such as a monoclonal antibody, will recognize binding sites that are unique to the target cell and allow the particle to dock onto the exposed surface. Additional target sites on cell surfaces could be receptor glycoproteins that are capable of recdognizing phosphorylated mannooligosaccharide structures (a typical example is the Mannose 6-phosphate receptor MPR 300, Mr 300 kDa that is capable of recognizing lysosomal enzymes that contain these structures and internalize them (Khan et al 2012). For successful delivery, carriers must: (i) form condensed complexes with biomolecules, (ii) facilitate penetration of the cell membrane after complexation, and (iii) unload their payloads inside of cells. The current research in the fields of nanoparticles and drug delivery systems are focusing into developing strategies for targeting nanoparticles to the site of drug action. A fusion protein will instigate the process of merging with the target cell, thereby bringing the particle into the cytoplasm. As polymeric nanoparticles are recognized as foreign by the body’s immune system, they are removed quite effectively by phagocytosis on exposure to the endoreticular system. This will prevent the particle from reaching the target site and must be prevented. Steps toward this goal have already been taken with the production of so-called “stealth”nanoparticles. These are nanoparticles which incorporate a biomimetic polymer, usually polyethylene glycol, into their structure to avoid elicitation of an immune response. Presently, such an idealized nanoparticle with these three important properties has yet to be realized, but attempts have been made to attach some of the subsystems described.

Strychnos (Loganiaceae) comprises of about 200 species distributed in three geographic regions, Central and South America (~73 species), Africa (~75 species), Asia including Australia and Polynesia (about ~44 species). The genus Strychnos is very well known for its medicinal chemistry and has long been studied for its pharmacological, analgesic and antipyretic properties.

In recent years polysaccharide nanoparticles are being extensively used in various fields of biology and medicine. The importance of the Strychnos seed material that consists of both Galactomannan, Galactan have been described. The role of plant glycosidases in seeds and in particular reference to a a-mannosidases (their classification, occurrence, molecular properties and potential applications).

Strychnos potatorum Polysaccharides, Galactomannan and Galactan were extracted and used for the nanoparticles preparation. Thesese were characterized for size and morphology by Atomic Force Microscopy, Scanning Electronic Microscopy, and Transmission Electronic Microscopy. Nanoparticles from both Galactan and Galactomannan were successfully prepared by Sol-oil chemistry method. From the AFM images it is shown that the nanoparticles are spherical in shape for both polysaccharides, and from the images of SEM and TEM we found the size of galactomannan nanoparticles are varied from 45 nm to110 nm and the size of Galactan nanoparticles also from 37 nm to 100 nm, these nanoparticle can be used for many applications such as Drug delivery (Saif et al 2014).

References
  1. Adinolfi M, Corsaro MM, Lanzetta R, Parrilli M, Folkard G, Grant W, Sutherland J (1994) Composition of the coagulant polysaccharide fraction from Strychnos potatorum seeds. Carbohydrate Research, 263: 103-110.
  2. Jayaram K. Murthy IYLN, Lalhruaitluanga H, Prasad M.N.V. (2009) Biosorption of lead from aqueous solution by seed powder of Strychnos potatorum L. Colloids and Surfaces B: Biointerfaces 71, 248–254
  3. Jayaram KS (1993) Indian tree offers nuclear waste treatment. Nature, 365: 779
  4. Khan I and Kumar, N.S, (2012) Mannose 6-phosphate containing nanoparticles: preparation, characterization and interaction with cation independent mannose 6-phosphate /IGF-II Receptor (MPR300) J. of Bionanosciences. Vol.5,1-9, 2012
  5. Puvvada GVK, Chandrasekhar K (1997) Studies on the metal binding properties of seeds of Strychnos potatorum. NML technical journal, 39 (4): 239-247.
  6. Saif M.M.S., Khan I, Prasad M. N. V., and Kumar N.S, (2014) Preparation and Characterization of Strychnos potatorum L. Seed polysaccharide nanoparticles and af?nity matrices: relevance to biological applications. Advanced Science, Engineering and Medicine 6, 1–8, 2014
  7. Saif M.M.S., Kumar N.S, Prasad M.N.V. (2012) Binding of cadmium to Strychnos potatorum seed proteins in aqueous solution: Adsorption kinetics and relevance to water puri?cation, Colloids Surf. B: Biointerfaces 94, 73-79
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