NANO DRUG DELIVERY SYSTEM - A MINI REVIEW | Open Access Journals

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NANO DRUG DELIVERY SYSTEM - A MINI REVIEW

Avinash Guptha*

Mary Institute of Technology & Science, Keesara, Hyderabad, Telangana, India.

*Corresponding Author:
Avinash Guptha
Mary Institute of Technology & Science, Keesara, Hyderabad, Telangana, India

Received: 10 May 2015 Accepted: 11 June 2015

Visit for more related articles at Research & Reviews: Journal of Pharmaceutics and Nanotechnology

Introduction

Delivering therapeutic compound to the target site is a noteworthy issue in treatment of numerous diseases. A conventional application of drugs is characterized by limited effectiveness, poor bio distribution, and lack of selectivity [1 - 5]. These confinements and draw backs can be overcome by controlling drug delivery In controlled drug delivery systems [DDS] the drug is transported to the place of action, thus, its influence on vital tissues and undesirable side effects can be minimized.[6 - 10]

Also, DDS shields the medication from quick degradation or clearance and improves drug concentration in target tissues, along these lines, lower dosages of medication are obliged.[11 - 15] This advanced type of therapy is particularly critical when there is a discrepancy between a dose or centralization of a medication and its therapeutic results.[15 - 20]

Cell - specific targeting can be accomplished by appending drugs to individually designed carriers. Late improvements in nanotechnology have demonstrated that nanoparticles [structures smaller than 100 nm in at least one dimension] have an incredible potential as drug carriers.[20 - 23] Because of their small sizes, the nanostructures show unique physicochemical and biological properties [e.g., an enhanced reactive area as well as an ability to cross cell and tissue barriers] that make them a favorable material for biomedical application.[20 - 25]

Nano Carriers & Their Applications

Different Nano forms have been endeavored as drug delivery systems, changing from natural substances, for example, albumin, gelatin and phospholipids for liposomes, to synthetic substances, for example, different polymers and strong metal - containing Nanoparticles [24 - 28]. Polymer–drug conjugates, which have high size variety, are typically not considered as Nanoparticles. Be that as it may, since their size can at present be controlled inside of 100 nm, they are additionally included in these nanodelivery systems.[25 - 30] These Nano delivery systems can be intended to have medications absorbed or conjugated onto the molecule surface, typified inside the polymer/lipid or dissolved inside of the particle lattice. As an outcome, medications can be shielded from a discriminating situation.[29 - 33]

What's more, Nano carriers can be amassed specially at tumor, inflammatory and irresistible destinations by prudence of the enhanced permeability and retention [EPR] impact. The EPR impact includes site - particular qualities, not connected with ordinary tissues or organs, consequently bringing about expanded specific focusing on. In light of those properties, nanodrug delivery systems offer numerous points of advantages including. [34 - 39] Enhancing the stability of hydrophobic medications, rendering them suitable for organization; Enhancing bio distribution and pharmacokinetics, bringing about enhanced efficacy These are accumulate at target site so Diminishing adverse effects of drug. Diminishing harmfulness by utilizing biocompatible nanomaterial.[40 - 45]

Types Of Targeing

Passive targeting

Passive targeting on exploits the unique pathophysiological characteristics of tumor vessels, empowering nanodrugs to accumulate in tumor tissues. Regularly, tumor vessels are exceptionally disarranged and expanded with a high number of pores, bringing about broadened crevice gap junctions between endothelial cells and compromised lymphatic drainage.[46 - 49] The "leaky" vascularization, which alludes to the EPR impact, permits migration of macromolecules up to 400 nm in distance across into the encompassing tumor region.[50 - 55] Additionally, the EPR impact, the microenvironment encompassing tumor tissue, is not the same as that of healthy cells, a physiological phenomenon that likewise bolsters passive targeting on. Taking into account the high metabolic rate of quickly developing tumor cells, they require more oxygen and supplements. Hence, glycolysis is stimulated to get additional energy, bringing about an acidic environment [56 - 60].Taking point of interest of this, pH - delicate liposomes have been intended to be stable at physiological pH 7.4, however corrupted to release drug molecules at the acidic ph. [61 - 66]

Universally focusing on cells inside of a tumor is not generally plausible because a few medications can't diffuse efficiently, and the irregular way of the methodology makes it hard to control the procedure.[56 - 59] The passive targeting is restricted in light of the fact that certain tumors don't show an EPR impact, and the penetrability of vessels may not be the same all through a single tumor.[67 - 72]

Active Targeting

One approach to overcome the restrictions of passive targeting on is to append affinity ligands [antibodies,[73 - 75] peptides, aptamers or little molecules[76 - 80] that just tie to particular receptors on the cell surface] to the surface of the Nano carriers by a variety of conjugation chemistries.[81 - 86] Nano carriers will perceive and bind to target cells through ligand–receptor interactions by the epitopes on the cell surface.[87 - 90] So as to accomplish high specificity, those receptors ought to be exceedingly expressed on tumor cells, however not on normal cell. [26, 91 - 96]

Factors Effect On Drug Delivery

For effective drug delivery Nano carriers must have effective circulation time to prevent the elimination of drugs before reaching their target cell.[97 - 100]

particle size

Assumes a key part in particle capacities, for example, targeting, uptake mechanisms, clearance, degradation. Depend on particle size the diffusion, adhesion properties will alter resulting in different uptake efficiencies.[101 - 104] The extent of nanoparticles utilized in a drug delivery system should be large enough to prevent their rapid leakage into blood capillaries but small enough to escape capture by fixed macrophages that are lodged in the reticuloendothelial system [liver and spleen]. The size of the sinusoid in the spleen and fenestra of the Kuffer cells in the liver fluctuate from 150 to 200 nm [105 - 109] and the size of gap junction between endothelial cells of the leaky tumor vasculature may fluctuate from 100 to 600 nm [110 - 113]. Consequently, the size of nanoparticles should be up to 100 nm to reach tumor tissues by passing through these two particular vascular structures.[44 - 48, 114 - 119]

Surface Characteristics

Along with their size, the surface characteristics of nanoparticles are also an important factor. these are determine circulation time of nanoparticles. Nanoparticles should ideally have a hydrophilic surface to escape macrophage capture [46,120]. This can be accomplished by coating the surface of nanoparticles with a hydrophilic polymer, such as PEG, protects them from opsonization by repelling plasma proteins.[89,92,121 - 125]

Nano Carriers

Nano Crystals

A standout amongst the most clear and vital nanotechnology tools for product advancement is the chance to change over existing medications with poor water solubility and dissolution rate into promptly water - dissolvable dispersions by changing over them into Nano sized drugs.as such, the medication itself may be defined at a nano scale such that it can work as its own 'carrier'. [126 - 129]Many methodologies have been considered, yet the most reasonable technique includes diminishing the medication molecule size to nanometer range and balancing out the medication NP surface with a layer of nonionic surfactants or polymeric macromolecules. By diminishing the particle size of the active pharmaceutical ingredient, the drug's surface range is expanded significantly, subsequently enhancing its solvency and disintegration and therefore expanding both the greatest plasma concentration and area under the curve.[12,130 - 132] When the medication is nano sized, it can be formulated into various dosage forms, for example, oral, nasal and injectable. These nano crystal medications may have advantages over association colloids [micelle arrangements] because the level of surfactant per measure of medication can be incredibly minimized, utilizing just the sum that is important to stabilize the solid–fluid interface.[133 - 138]

Besides, late studies have demonstrated that external agents, for example, surfactants, for nanocrystal drug delivery can be eliminated. For instance, a strategy was as of recently created for the conveyance of a hydrophobic photosensitizing anticancer medication in its pure form utilizing nanocrystals.[17,139 - 142] Synthesized by the reprecipitation technique, the subsequent medication nanocrystals were stable in aqueous dispersion, without the need of any extra stabilizer.[143] An in vivo study of the nanocrystal drug also showed significant efficacy compared with the conventional surfactant - based delivery system.[61 - 64, 144 - 149]

Inorganic Nanoparticles

Inorganic nanoparticles can be characterized as particles of metal oxide or metallic composition having no less than one length scale in the nanometer range.[65 - 69] These nanostructures show altogether novel and particular chemical, physical, and natural properties, and usefulness because of their nanoscale size, have evoked much interest.[70, 150 - 156]

Au Nanoparticles

Au Nanoparticles Noble metal Nanoparticles, for example, Au Nanoparticles, have developed as a promising platform for medication and quality conveyance in that they give a valuable supplement to more traditional delivery vehicles.[71 - 75,157 - 160] The blend of inertness and low toxicity, simple union, substantial surface area, entrenched surface functionalization [by and large through thiol linkages] and tunable solidness furnish Au Nanoparticles with remarkable credits to empower new delivery methodologies. Besides, excess loading of pharmaceuticals on Nanoparticles permits 'medication stores' to gather for controlled and maintained discharge, in this way keeping up the medication level inside of the therapeutic window.[76 - 78, 161 - 166]

Superparamagnetic Nanoparticles Magnetic Nanoparticles

The superparamagnetic properties of iron [II] oxide particles can be utilized to guide microcapsules set up for conveyance by external magnetic fields. Another favorable position of utilizing magnetic Nanoparticles is the capacity to warmth the particles after internalization, which is known as the hyperthermia impact.[89 - 92, 167 - 169] Other than being used for focusing on and raising temperature, magnetic Nanoparticles can likewise influence the porousness of microcapsules by applying external oscillating magnetic fields and discharging exemplified materials.[83 - 86] for instance, ferromagnetic Au - covered cobalt Nanoparticles [3 nm in breadth] were fused into the polymer walls of microcapsules. Accordingly, use of external alternating magnetic fields of 100–300 Hz and 1200 Oe quality irritated the capsule wallstructures and drastically expanded their porousness to macromolecule.[87 - 90 170 - 173]

Clay Nanoparticles Ceramic Nanoparticles

Clay Nanoparticles Ceramic Nanoparticles are particles manufactured from inorganic mixes with permeable attributes, for example, silica, alumina and titania.[91] Among these, silica Nanoparticles have pulled in much research consideration as a consequence of their biocompatibility and simplicity of blend, and surface modification.[92 - 95, 174 - 179] Furthermore, the entrenched silane science encourages the cross - connecting of medications to silica particles.[180]

Carbon - based Nanomaterials

Carbon - based nanomaterials have pulled specifically intrigue in light of the fact that they can be surface functionalized for the joining of nucleic acids, peptides and proteins. Carbon nanotubes [CNTs], fullerene, and nanodiamonds[96 - 99, 181 - 186] have been widely concentrated on for medication conveyance applications.[100] The size, geometry and surface qualities of single - divider nanotubes [SWNTs], multiwall nanotubes and C60 fullerenes make them engaging for medication bearer utilization.[187 - 190]

However, the essential downside of carbon - based nanomaterials seems, by all accounts, to be their harmfulness. Investigations have demonstrated that CNTs can prompt cell expansion hindrance and apoptosis. [85,191 - 193] In spite of the fact that they are less harmful than carbon strands and Nanoparticles, the poisonous quality of CNTs increments altogether when carbonyl, carboxyl and/or hydroxyl utilitarian gatherings are available on their surface However, the essential disadvantage of carbon - based nanomaterial seems, by all accounts, to be their danger. Analyses have demonstrated that CNTs can prompt cell expansion restraint and apoptosis. Despite the fact that they are less dangerous than carbon strands and Nanoparticles, the lethality of CNTs increments essentially when carbonyl, carboxyl and/or hydroxyl utilitarian gatherings are available on their surface.[106 - 108, 194 - 199]

Liposomes

Liposomes are the most clinically established Nano systems for drug delivery. Their efficacy has been demonstrated in reducing systemic effects and toxicity, as well as in attenuating drug clearance. [109 - 111, 200 - 204] Modified liposomes at the nanoscale have been shown to have excellent pharmacokinetic profiles for the delivery of DNA, antisense oligonucleotide, siRNA, proteins and chemotherapeutic agents. Doxorubicin is an anticancer medication that is generally utilized for the treatment of different sorts of tumors. It is an exceptionally dangerous compound influencing tumor tissue, as well as heart and kidney, a truth that restrains its restorative applications.[112 - 116, 205 - 209] On the other hand, the advancement of doxorubicin encased in liposomes finished in an affirmed nanomedical medication conveyance system. This novel liposomal definition has brought about decreased conveyance of doxorubicin to the heart and renal framework, while hoisting the amassing in tumor tissue[23,24] by the EPR impact. Moreover, various liposomal medications are presently being explored, including anticancer specialists, for example, camptothecin [25] and paclitaxel [PTX],[26] and also anti - toxins, for example, vancomycin[27] and amikacin.[210 - 214]

Liposomes are also subject to some limitations, including low encapsulation efficiency, fast burst release of drugs, poor storage stability and lack of tunable triggers for drug release. [117 - 120] Furthermore, since liposomes cannot usually permeate cells, drugs are released into the extracellular fluid.[215 - 218]

Polymeric Nanoparticles

Polymeric Nanoparticles are colloidal particles with a size scope of 10–1000 nm, and they can be round, extended or core–shell structures. They have been manufactured utilizing biodegradable engineered polymers, for example, polylactide–polyglycolide copolymers, polyacrylates and polycaprolactones, or common polymers, for example, egg whites, gelatin, alginate, collagen and chitosan.[42] Various routines, for example, dissolvable dissipation, unconstrained emulsification, dissolvable dissemination, salting out/emulsification - dispersion, utilization of supercritical CO2 and polymerization, have been utilized to set up the Nanoparticles.[121 - 125, 219 - 222] Polymeric Nano carriers can be classified in light of three medication consolidation components. The primary incorporates polymeric transporters that utilization covalent science for direct medication conjugation [e.g., straight polymers]. The second gathering incorporates hydrophobic collaborations in the middle of medications and Nano carriers [e.g., polymeric micelles from amphiphilic piece copolymers].[126] Polymeric Nano carriers in the third gathering incorporate hydrogels, which offer a water - filled warehouse for hydrophilic medication exemplification.[127 - 130,223 - 224]

Polymer–Drug Conjugates [Prodrugs]

Many polymer–drug conjugates have been produced subsequent to the first mix reported in the 1970s.[44,45] Conjugation of macromolecular polymers to medications can altogether upgrade the blood course time of the medications. Particularly, protein or peptide drugs, which can be promptly processed inside the human body, can keep up their action by conjugation of the water - dissolvable polymer PEG [PEGylation].[131 - 134] For instance, it was accounted for that PEGylated L - asparaginase expanded its plasma half - life by up to 357 h.[225] Without PEG, the half - existence of normal L - asparaginase is just 20 h. Notwithstanding PEGylation of proteins, little sub - atomic anticancer medications can likewise be PEGylated to enhance their pharmacokinetics for cancer therapy. For example, PEG - camptothecin [PROTHECAN®] has entered clinical trials for cancer therapy.[135 - 138]

Polymeric Micelles

Polymeric micelles are formed when amphiphilic surfactants or polymeric molecules spontaneously associate in aqueous medium to form core–shell structures. The inner core of a micelle, which is hydrophobic, is surrounded by a shell of hydrophilic polymers, such as PEG.[139] Their hydrophobic core serves as a reservoir for poorly water - soluble and amphiphilic drugs; at the same time, their hydrophilic shell stabilizes the core, prolongs circulation time in blood and increases accumulation in tumor tissues.[140 - 142]

Hydrogel Nanoparticles

Hydrogel Nanoparticles as of late, hydrogel Nanoparticles have increased impressive consideration as a standout amongst the most encouraging nano particulate drug conveyance frameworks inferable from their remarkable properties. Hydrogels are cross - connected systems of hydrophilic polymers that can retain and hold more than 20% of their weight in water, while in the meantime, keeping up the particular 3D structure of the polymer system. Swelling properties, system structure, porousness or mechanical steadiness of hydrogels can be controlled by outside boosts or physiological parameters.[74–78] Hydrogels have been broadly contemplated for controlled arrival of therapeutics, jolts responsive discharge and applications in organic implants.[75,79–81] However, the hydration reaction to changes in boosts in most hydrogel frameworks is too moderate for helpful applications. To conquer this constraint, further improvement of hydrogel structures at the small scale and nano - scale is require. Late reports demonstrated some advancement in miniaturized scale and nanogels of poly - N - isopropylacrylamide with ultrafast reactions and appealing rheological properties.[83,84] Ding et al. exhibited that cisplatin - stacked polyacrylic corrosive hydrogel Nanoparticles could be embedded and put on tumor tissue.[226] This hydrogel framework displayed unrivaled adequacy in hindering tumor development and delaying lifespan in mice. [143 - 144] The in vivo biodistribution test likewise exhibited that the hydrogel insert brings about high focus and maintenance of the medication. A multifunctional crossover hydrogel was produced by consolidating the attractive properties of Nanoparticles and the run of the mill qualities of the hydrogel. These crossover hydrogels could be utilized to load an expansive number of medications and transport them to the objective site by the utilization of an outer attractive field.[227 - 229]

Dendrimers

Dendrimers are engineered, fanned macromolecules that shape a tree - like structure. Dissimilar to most straight polymers, the compound organization and sub - atomic weight of dendrimers can be absolutely controlled; consequently, it is moderately simple to anticipate their biocompatibility and pharmacokinetics.[95] Dendrimers are exceptionally uniform with to a great degree low polydispersities, and they are normally made with measurements incrementally developed in rough nanometer ventures from 1 to more than 10 nm.[145] Their globular structures and the vicinity of inward holes empower medications to be epitomized inside of the macromolecule inside and are utilized to give controlled discharge from the internal core.[96] Although the little size [up to 10 nm] of dendrimers points of confinement broad medication consolidation, their dendritic nature and fanning permits medication stacking onto the outside surface of the structure[97] through covalent tying or electrostatic communications.[146,230]

Conclusion

Nano carriers as drug delivery systems are intended to enhance the pharmacological and therapeutic properties of conventional drugs. The incorporation of drug molecules into nanocarrier can secure a medication from degradation and in addition offers possibilities of targeting and controlled release. Because of small dimensions, Nano carriers are able to cross the blood - brain - barrier[BBB] and operate on cellular level. In correlation with the conventional type of medications, nanocarrier - drug conjugates are more effective and selective. They can reduce the toxicity and other adverse side effects in normal tissues by accumulating drugs in target sites. In consequence, the required doses of drugs are lower. A conceptual understanding of biological responses to nanomaterials is needed to develop and apply safe nanomaterials in drug delivery later on. Moreover a close collaboration between those working in drug delivery and particle toxicology is necessary for the exchange of ideas, systems and ability to go places with this issue.

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