DENDRIMERS IS A SMART NOVEL CARRIER IN DRUG DELIVERY: AN INSIGHT

DENDRIMERS IS A SMART NOVEL CARRIER IN DRUG DELIVERY: AN INSIGHT

Suman *, Saddam, Shashi Alok and Ram Narayan Prajapati

Institute of Pharmacy, Bundelkhand University, Jhansi, Uttar Pradesh, India.

ABSTRACT: Multifunctional, versatile materials with multiple dendrimer branches have myriad binding sites and are in high demand for their drug binding, loading potential, and coatings. Dendrimers are among the latest generations of nano-systems that are potential drug carriers. Dendrimer chemistry is one of modern chemistry's most captivating and fastest-growing areas. Dendrimer research has grown exponentially in recent decades, from synthesis to application. The distinctive structural features of dendrimers include their nanoscopic size, multi-functionalized surface, strong branching, cavernous interior, etc., which makes dendrimers themselves ideal drug carriers. Dendrimer provides a unique platform for drug attachment that can bind and release drugs through several mechanisms. Developing new smart materials and tracking their structural potential have been focused on curing disease. Other applications, such as catalyzing biomolecules like proteins and selective API pharmaceuticals of toxic metals, dyes, and pesticides, have been thrust research areas in materials and pharmaceutical sciences. In recent years Dendrimers have received significant consideration as drug delivery carriers. As a drug delivery agent, Dendrimer is a promising, safe, and selective option. The essential property of dendrimers is their highly selective nature for targeting the desired tissue, which holds a promising future for treating several disorders. Their safe, non-toxic, and biocompatible nature makes them appropriate for site-specific as well as prolonged drug delivery carriers.

Keywords: Nano system, Dendrimer, Smart drug delivery, Novel carrier, etc

INTRODUCTION:

Nanotechnology: Pharmaceutical nanotechnology is the instigative, fleetly arising medical science branch that binds nanoscale accouterments asmedicine delivery and/ or discriminating tools. As medicine delivery tools, nano-delivery systems can be used to enhance the point-specific, targeted delivery of specific drugs. Nanotechnological systems are bioactive motes’ delivery systems for remedial purposes and towel imaging.

Likewise, new scientific studies combine nano-system operations for coexistent complaint treatment and monitoring affection progression, helping the clinical doctor to get the most accurate determination. The examination aims to develop new drugs grounded on bioactive patch delivery with nano-systems and in a geometric increase of drugs presently in clinical studies.

The pharmaceutical assiduity follows the same path, investing in bioactive patch development from a pharmaceutical nanotechnology point of view. Nanotechnology is the study of controlling matter on a snippet and molecular scale. Generally, nanotechnology deals with structures between 1- 100 nanometres in at least one dimension and involves modifying or developing accouterments within that size. It makes the material lighter, stronger, brisk, lower, and more durable. Pharmaceutical nanotechnology exploration aims to develop new drugs grounded on bioactive patch delivery with nano-systems and in a geometric increase of drugs presently in clinical studies. The pharmaceutical industriousness follows the same path, investing in bioactive particle development from a pharmaceutical nanotechnology point of view ¹. Nanotechnology has surfaced to be an area of active examination, especially in its operations in drugs ². The nanoscale manipulation allows optimal targeting and delivery as well as the controllable release of medicines or imaging agents ³. Among all the operations of nanotechnology in drug, nanocarrier-supported medicine delivery system has attracted significant exploration interest due to their great translational value. The small size of the nanocarriers can help medicines overcome certain natural walls to reach diseased areas ^{4, 5}. Taking advantage of different nano-sized accouterments and colorful structures, nanocarriers can help inadequately answerable medicines become more bioavailable and cover fluently degraded curatives from declination ⁶. In addition, the adjustable shells of nanocarriers also expand their usability in different biomedical operations, especially in targeted curative. Indeed, their remaking can’t only stabilize but also functionalize them to be responsive to different stimulants, enhancing the remedial efficacity ⁷. Herein we review recent advances in the development and operations of colorful nanocarriers, agitating their advantages and disadvantages in terms of their different compositions as well as different functionalization methodologies ⁸.

Various Types of Nanocarrier Drug Delivery Systems ⁹:

Dendrimers: The term dendrimer comes from the Greek words dendron (= tree) and Mero’s (= part) and describes a new group of branched macromolecules whose infrastructure looks like a tree. In 1985, Donald Tomalia and his coworkers published the composition and full characterization of a new Poly amidoamine (PAMAM) macromolecular group called dendrimers. Since, the first dendrimer was reported in 1978 by Fritz Vogtle, dendrimer exploration has grown exponentially, from conflation to exercise, in the once four decades. Dendrimers are made up of a starting molecule similar to nitrogen, to which a repeating series of chemical responses add carbon and another element to produce a chemical branching structure. Dendrimers get curtly packed as they extend out to the circumference, forming an unrestricted membrane-like structure. Dendrimers are specially designed and manufactured for a wide variety of exercises, including the treatment of cancer, medicine delivery, catalysis, gene transfixion, energy harvesting, and photoactivity. Dendrimers carrying different accouterments and their branches can do several effects simultaneously, similar to perceiving diseased cells, diagnosing diseased states including cell death, medicine delivery, describing the position, and reporting events of therapeutic ^{10, 11}. Dendrimers formulation of delivery is one of the most grueling and seductive experimenters for pharmaceutical scientists. The use of non-ionic or ionic biodegradable polymers in waterless solutions and colloidal medication forms similar to liposomes, nanoparticles, microspheres, microemulsions, resealed erythrocytes, microcapsules, and dendrimers have been studied to overcome the medicine delivery problems and enhance the point targeting as well as release rate and side effect. Dendrimers as medicine delivery agents are a promising, safe, effective, and picky medicine delivery option. This review covers some introductory information about dendrimers medication methodologies and further about their possible exercise in colorful areas similar as the biomedical field, remedial agent, individual agent, gene transcript, targeted medicine delivery, solubility enhancer, catalyst, complements, publishing write-up, biography mimics and numerous other areas of wisdom. The dendrimer’s exercises in the biomedical field show high progress in the future of dendrimers. Dendrimers are made up of a starting snippet similar to nitrogen, to which a repeating series of chemical responses add carbon and another element to produce a chemical branching structure. Dendrimers come densely packed as they extend to the fringe, forming an unrestricted membrane-like structure.

FIG. 1: STRUCTURE OF THE DENDRIMER

Structure of Dendrimer: The structure of a dendrimer consists of three different components they are:

Central Core: The central core should contain a relative functional group.

Repeated Branches: The repeated branch should organize in a series of generations.

Surface Functional Groups: The surface functional group should determine molecules' physical properties and location ¹².

Properties of Dendrimers ¹³:

• Dendrimers have compact and Globular structures.
• Dendrimers are synthesized carefully and in a stepwise manner.
• Dendrimers have high structural control.
• Dendrimers have well-defined architecture.
• Dendrimers are monodispersed and highly branched macromolecules with precise molecular weight, shape, and size.
• Dendrimers have surface functional groups for drug conjugation and inner cavities for the entrapment of drugs.
• Dendrimer has lower glass temperatures.

Various Types of Dendrimers ¹⁴:

Dendrimer expression enhances the efficacity, effectiveness, and safety of the medicine. Dendrimers have ideal properties which are useful in targeted medicine delivery systems. One of the most effective cell-specific targeting agents delivered by dendrimers is folic acid PAMAM dendrimers modified with carboxy methyl PEG 5000 exterior chains revealed reasonable medicine lading and a reduced release rate reduced hemolytic toxin conferred with the non-PEGylated dendrimer. To prepare sustained/ Prolong delivery of remedial agents in targeted medicine delivery systems to minimize patient compliance and step-down hepatic first pass and chemical declination similar to protein, enzymes, and contagions so the good amplitude of dendrimer in the biomedical fields. The other objects of the dendrimer are the individual reagent for tumor imaging by glamorous resonance imaging and as a different agent, by varying the size hydrophilicity, and by combining with tumor-targeting antibodies. These composites can be used for a range of specific imaging purposes.

FIG. 2: GENERATION GROWTH OF DENDRIMER

Methods for the Synthesis of Dendrimers ^{15, 16}: Some following methods are generally used for the synthesis of dendrimers.

Divergent Growth Method: The divergent methodology starts from the central core and extended toward the outside; the central core contains a relative functional group.

The divergent technique is multifunctional and accretive fusion. In the original step, core particle like EDA and ethylene diamine is taken and with the help of Michael’s addition response, four arms of nitrogen are attached to EDA.

In the alternate step, EDA is again responded with an amination response; this step may repeat multiple times to gain discriminational generation of the dendrimer.

Each step of the divergent technique should be completed to avoid misjudgments in a generation because if some branches remain shorter as compared to other branches may cause contaminations, functionality, and proportion of the dendrimer ^{17, 18, 19, 20, 21}.

FIG. 3: DIVERGENT GROWTH METHOD ²²

Convergent Method: This system overcomes the immaculacy and structural faults issues of divergent conflation. Symmetric and invariant dendrimers are synthesized by the coincident system, but the overall yield is less. The yield is reduced for the uniformity of the immaculacy as well as it's laboratory-scale dendrimer conflation. For large scale, the most divergent system is preferred. In the coincident conflation system, the dendron ends up in a terminal group that’s conflation originally. The final step links with the core material for complete structure conformation; due to the steric interference between the dendron and the core, the size attained in the coincident system is limited. This limitation isn't observed in dendrimer conflation. The alternate system is the coincident growth process that works inwards by linking face units together gradationally. When the growing wedges are large enough, several are attached to a suitable core to give a complete dendrimer. Dendrimers are made up of a starting molecule, similar to nitrogen, to which carbon and other elements are added by a repeating series of chemical responses that produce a globular branching structure. As the process replications, consecutive layers are added. It possesses three distinguished architectural ingredients ^{23, 24}.

1. An Originator Core:
2. Interior layers (generations) are composed of repeating units radically attached to the interior core. Exterior terminal functionality is attached to the remotest interior generations ^{25, 26}.

Mechanism of Dendrimer-drug Interactions: Medicine atoms may be covalently conjugated to the end groups of a dendrimer or entangled inside the core via hydrogen adhesion, hydrophobic bearing, or electrostatic relations. The number of generations influences the medicine lading capacity; a fairly high generation number provides further space for guest medicines and has a larger number of functional groups on the face for medicine conjugation. PPI, PAMAM, PLL, polypeptide, polyesters, polyether dendrimers, and dendrimers grounded on PEG, or carbohydrates, have been substantially delved for the delivery of the anticancer medicine.

The anticancer drug interacts with dendrimers via three different mechanisms, i.e.

1. Physical encapsulation,
2. Electrostatic interaction,
3. Covalent conjugation

Physical Encapsulation: Due to their spherical shape, unfilled internal cavities, and structural design, dendrimers can directly encapsulate guest molecules into the macromolecule interior.

The empty internal cavities of dendrimers are hydrophobic and interact with poorly soluble drugs through hydrophobic interaction.

FIG. 4: DRUG ENCAPSULATION IN DENDRIMERS BY PHYSICAL ENCAPSULATION

Electrostatic Interactions: Many amine and carboxyl groups on the face of dendrimers have implicit exercises in enhancing the solubility of hydrophobic medicines by electrostatic relation. Some medicines with carboxyl groups like ibuprofen, ketoprofen, diflunisal, naproxen, and indomethacin have been perplexed with dendrimers by electrostatic relations. Through electrostatic relations, colourful ionizable medicines form complexes with the multifunctional face of dendrimers having many ionizable terminating face batches ^{27, 28}.

Covalent Conjugation: Large numbers of functional groups on the face of dendrimers make them suitable for the covalent conjugation of multitudinous medicines with applicable functional groups.

In the case when the medicine is covalently bound to dendrimers, its release occurs through chemical or enzymatic fractionalization of hydrolytically labile bonds ²⁹ also, the medicines can be covalently conjugated to dendrimers through some spacers that may include PEG, p- amino benzoic acid, p- amino hippuric acid, lauryl chains, etc., or biodegradable connection similar to amide or ester bonds. This prodrug approach has been set up to increase the stability of medicines and has affected their release kinetics significantly ³⁰.

Application of Dendrimers ^{31, 32}:

Therapeutic Application:

• Dendrimer in photodynamic therapy
• Dendrimers for Boron Neutron capture therapy

Diagnostic Application:

• Dendrimers as MRI contrast agent
• Dendrimers as X-Ray contrast
• Dendrimer as molecular probe agent

Pharmaceutical Application ³³:

• Dendrimers in pulmonary drug delivery
• Dendrimers in Transdermal drug delivery
• Dendrimers in ocular drug delivery
• Dendrimers in oral drug delivery
• Dendrimers for controlled-release drug delivery
• Dendrimers in targeted drug delivery
• Dendrimers in gene delivery
• Dendrimers as a solubility enhancer
• Cellular delivery using dendrimers carrier
• Dendrimer-basedproducts in cosmetics
• Dendrimer-based commercial products

Pharmaceutical Applications ^{34, 35, 36}:

Dendrimers in Pulmonary Drug Delivery: Dendrimers have been reported for pulmonary medicine delivery of Enoxaparin by 40 G2 and G3 generation appreciatively charged PAMAM dendrimers were reported to increase the relative bioavailability of Enoxaparin. The appreciatively charged dendrimer, which was effective in deep mode thrombosis forms a complex with enoxaparin after pulmonary administration ³⁷.

Dendrimer in Transdermal Drug Delivery: Dendrimers have been innovating to enhance solubility and plasma revolution time via transdermal formulations and deliver medicines efficiently. To ameliorate the medicine intimation through the skin as penetration enhancers PAMAM dendrimer complex with NSAIDs has been reported.3.4- and 3.2- times advanced intimation has been shown when Ketoprofen and Diflunisal were conjugated with G5 PAMAM dendrimer. Enhanced bioavailability of PAMAM dendrimers by using indomethacin as the model medicine in transdermal medicine exercise was reported to be effective ^{38, 39}.

Dendrimer in Oral Drug Delivery: Oral Medicine delivery studies using the mortal colon adenocarcinoma cell line, CaCo2, have indicated that low- generation PAMAM dendrimers cross cell membranes, presumably through a combination of two processes, i.e., paracellular transport and adsorptive endocytosis. Remarkably, the glycoprotein efflux transporter doesn't appear to affect dendrimers, thus medicine dendrimer complexes can bypass the efflux transporter. PAMAM dendrimers conjugated with folic acid and fluoresce in isothiocyanate for targeting the tumour cells and imaging independently. DNA- assembled dendrimer conjugates may allow the combination of different medicines with different targeting and imaging agents ^{40, 41}.

Dendrimer Hydrogel for Ocular Drug Delivery: Dendrimers are especially ideal for synthesizing hydrogels, cross-linked networks that increase in volume in a waterless solution and are moreanalogous to living tissue than any other synthetic admixture. These hydrogels have exercises by adding polyethylene glycol or PEG groups to the dendrimers, including cartilage tissue products and sealing ophthalmic injuries. Synthesizing a hydrogel composed of PEGylated dendrimers that contain optical medicine atoms attached to the dendrimers efficiently delivers the medicines to the eye ^42.

Dendrimers for Controlled Release Drug Delivery: The anticancer medicines Adriamycin and methotrexate were recapitulated into PAMAM dendrimers (i.e., G = 3 and 4) which had been modified with PEG monomethyl ether chains (i.e., 550 and 2000 Da independently) attached to their exteriors. An analogous construct involving PEG chains and PAMAM dendrimers was used to deliver the anticancer medicine 5 fluorouracil. Encapsulation of 5- fluorouracil into G4 increases in the cytotoxicity and saturation of dendrimers. The before-bandied dendrimer medicine intercourse methodologies are used to control medicine delivery. A third-generation dendritic unimolecular micelle with indomethacin entangled as a model medicine gives slow and sustained in vitro release compared to cellulose membrane control. Controlled release of the Flurbiprofen could be achieved by arranging a complex with amine-terminated generation 4 PAMAM Dendrimers ^{43, 44}.

Dendrimers in Targeted Drug Delivery: Dendrimers have ideal properties approved for application in targeted drug delivery systems. One of the most effective cell-specific targeting agents delivered by dendrimers is folic acid PAMAM dendrimers modified with carboxymethyl PEG5000 surface chains possessed reasonable drug loading, a reduced release rate, and reduced hemolytic toxicity compared with the non-PEGylated dendrimer ^{45, 46}. The star polymer was reported to give the most promising results regarding cytotoxicity and systemic circulatory half-life (72 hrs). In addition to perfecting medicine properties similar to solubility and tube rotation time, polymeric carriers can also grease the unresistant targeting of medicines to solid tumours. Combined these factors lead to the picky accumulation of macromolecules in tumor tissue, a caution nominated the ‘Enhanced Saturation and Retention’(EPR) effect. Thus, the anticancer medicine doxorubicin was reported to be covalently bound to this carrier via an acid- labile hydrazone relation. The cytotoxicity of doxorubicin was significantly reduced (80 – 98), and the medicine was successfully taken up by several cancer cell lines ^{47, 48}.

Dendrimers as Anticancer Drug Carriers: Original studies of dendrimers as implicit delivery systems concentrated on their use as unimolecular micelles and “dendriticboxes” for the noncovalent encapsulation of medicine particles. For sample, in early studies, DNA was perplexed with PAMAM Dendrimers for gene operations ⁴⁹. And hydrophobic medicines and be paintparticles were commercial in colorful dendrimer cores. An advantage of using dendritic unimolecular micelles rather than conventional polymeric micelles is that the micellar structure is maintained at all attention because the hydrophobic parts are covalently connected. Still, this approach suffers from a general debit in that it’s delicate to control their parcel of motes from the dendrimer core in some cases, harsh conditions are needed, whereas in others the reprised isn't well retained and motes are released fleetly. PAMAM dendrimers gave conjugates that displayed slower release, advanced accumulation in solid tumors, and lower toxin compared to free cisplatin ⁵⁰.

Sensors: The unique structures and parcels of dendrimers evolved interest in uniting nanoscale dendrimers in the seeing of chemical and natural species. It's on record that colorful nanoparticles are used to develop miniaturized, rapid-fire, ultrasensitive, and affordable environmental monitoring bias. Touzani reported that a Poly (Amidoamine) dendrimer with 1,8- Naphthalin amide face groups can act as a Photoinduced Electron Transfer (FET) fluorescent detector for rare earth matter and matter cations; his examination showed that the presence of matter ions evolves a Photoinduced Electron Transfer (PET) leading to an improvement in the luminescence ⁵¹.

Therapeutic Activity of Dendrimers: Dendrimers are being evolved as topical antimicrobial agents following the investigation of the effectiveness of polylysine dendrimers against herpes simplex germicide (HSV), presently under Phase II clinical trials for its efficacity against vaginal infection. SPL7013 Gel (Viva Gel ®) developed by Starpharma Pty Ltd (Melbourne, Australia) is a vaginal toxic for the forestallment of HIV and HSV infections. The active component of this Carbopol- grounded waterless gel is a dendrimer comprising a divalent benzhydryl amine (BHA) core, four generations of lysine branches with the remotest branches limited with a totality of 32 naphthalene di sulfonic acid groups that conduct hydrophobicity, and a high anionic charge to the dendrimer face ⁵².

The success of VivaGel®(Starpharma) gave a Philip to the other possible exercises of dendrimers. Wang et al. assessed the technique of antimicrobial exertion of PAMAM dendrimers in a guinea pig model of chorioamnionitis. E coli- convinced thrusting uterine infection. The authors attributed the antimicrobial exertion to the commerce of polycationic dendrimers with polyanionic lipopolysaccharide present in E. coli ⁵³. latterly it was observed that 3.5 G PAMAM dendrimers glycosylated with glucosamine displayed anti-inflammatory exertion by an inhibiting complex of lipopolysaccharide, expense- suchlike receptor 4(TLR4), and MD- 2, which mediates the proinflammatory cytokine responses ⁵⁴. This activity of incompletely glycosylated dendrimers could give a platform for the investigation of dendrimers in the treatment of malignancy, seditious complications, and contagious complications.

Reduction of Toxicity: Although dendrimers with cationic face groups beget cytotoxicity and hemolytic toxin yet their toxin can be soothed by remakingface groups with biocompatible ligands like PEG, acetyl group, carbohydrates, amino acids, and peptides, etc. The face engineering of dendrimers results in biocompatible dendrimers as well as reduces the toxin of some cytotoxic and haemolyticbioactive ^{55, 56}. Dendrimers show face charge-, attention- and generation-dependent cytotoxicity. The permeability profile of dendrimers is also related to their face charge. Cationic dendrimers are more poisonoushemolytic, cytotoxic, cytotoxicand more passable than anionic and neutral dendrimers. Designing of biocompatible and biodegradable dendrimers either by synthesizing dendrimers from biocompatible units(peptides, amino acids, carbohydrates, etc.), or modifying the face of cationic dendrimers with biocompatible ligands (PEGylation, acetylation, glycosylation, etc.), will facilitate a reduction intoxin ⁵⁷.

Dendrimers in Gene Transfection: Gene transfection is a direct approach where DNA is coupled to a nanoparticle of inert solid, directly targeted to the cell central. This process has come an important precious tool in molecular biology for studying mutations and regulation processes of genes or converting over-expression of asked proteins ⁵⁸. The ideal vector for transfection should have high effectiveness, be immunogenic, non-toxic, either biodegradable or excretable, and has a long blood rotation time. PAMAM dendrimers were the first setup to be tested as inheritable material carriers. Amino-terminated PAMAM or PPI dendrimers have been reported as nonviral gene transfer agents, enhancing DNA transfection by endocytosis and, eventually, into the cell center. A commercially available transfection reagent called Super Fact TM consists of actuated dendrimers. These actuated dendrimers can carry a larger quantum of inheritable material than contagions. Super Fect- DNA complexes are characterized by high stability and give more effective transport of DNA into the nexus than liposomes. The high transfection effectiveness of dendrimers may be due to their well-defined shape and the low pKa of the amines (3.9 and 6.9), which permit the dendrimer to buffer the pH change in the endosomal cube. PAMAM dendrimers functionalized with cyclodextrin showed luciferase gene expression about 100 times more advanced than unfunctionalized PAMAM or non-covalent fusions of PAMAM and cyclodextrin. It should be noted that dendrimers of high structural inflexibility and incompletely degraded high-generation dendrimers (i.e., hyperbranched infrastructures) appear more suited for certain gene delivery operations than complete high-generation symmetrical Dendrimers ⁵⁹.

Dendrimers for Additives, Printing Inks, and Paints: Dendrimers can be used in color material with complements, reducing the material demand of their liquid counterparts. Xerox Corp. A dry color emulsion dendrimer was patented as charge enhancing species in the form of a cumulative. An invariant adhesion of write-up to polar and non-polar foils was assured using dendritic polymers using complements in publishing inks ⁶⁰. Then, originally, the hyperbranched composites attach themselves to the color patches, and later large figures of functional groups which are remaining give adhesion to the face of the foils. A dendrimer is reliable for commerce between bulk and face material (glue, face coating, or polymer cross-linking ⁶¹. Dendritic polymers have also gained significance used in cabinetwork and automotive diligence. The polyurethane maquillages used then conduct face hardness, light fastness, scrape resistance, rainfall resistance, chemical resistance, and grandly shine properties.

Drug-Delivery Technique Using Dendrimers:

• Cancer-Targeted Delivery
• Antimicrobial Delivery
• Gene Delivery
• Oral Drug Delivery
• Vaccination
• Drug delivery by injection
• Transdermal Drug Delivery
• Dendrimers as MRI Contrast Agents
• Dendrimers as Tissue Regenerators
• Dendrimers in Cell Repair
• Dendrimers in Vaccine Development

Dendrimer in the Market: In July 2003, the FDA allowed the first clinical trials of a dendrimer- grounded pharmaceutical vivagel TM, a vaginal gel to help HIV. Currently, so numerous products like Stratus TMCS are used as cardiac labels prepared by Dade Behring, Superfec TM used for gene transfection made by Qiagen, and Alert Ticket TM prepared by US Army Research Laboratory used for anthrax discovery grounded on dendrimer accessible in the request. Most lately, Starpharma blazoned pre-clinical results in its docetaxel “Taxotere” program demonstrating significant advancements in anticancer efficacity and solubility improvement, offering implicit safety benefits of anticancer agents. The Swedish company Perstorp sells dendrimers- such as accouterments for various exercises, and high-performance shields for boats being only one sample. In the Netherlands, DSM has a new type of dendritic-grounded material that promises to reduce the number of pathways in the papermaking process, making it much more effective and environmentally friendly. Some other dendrimer-grounded products reaching marketable reality include Avidimers TM (Avidimer curatives, Ann Arbor, MI) for cancer forestallment and treatment and a gadolinium-grounded MRI difference agent. Starpharma, in collaboration with its US- grounded wholly- possessed company Dendritic Nanotechnologies (Mount Pleasant, MI), lately blazoned the marketable launch of its Priostar TM dendrimer- grounded technology exploration product called the NanoJuice Transfection tackle in addition to the Starburst and Priostar- grounded dendrimer family ⁶². Because of the presence of large figures of functional groups, these largely fanned dendrimers can bind with DNA. They will be useful for the transfection of DNA into a variety of delicate-to-transfect cells ⁶³.

Dendrimers in Drug Delivery ^{64, 65}:

Functionalization of Nanocarriers:

• The process of adding functional groups to the surface of the nanocarrier system is termed functionalization.
• It is necessary to control the nanocarrier-biosystem interaction during the drug delivery process and its targeting capacity.
• For instance, intracellular drug delivery specifically tailored nanoparticles will possess enhanced payload with binding capacity, specific cytotoxicity, and cellular internalization.
• Different methods are strategically employed for the surface functionalization of nanoparticles with different ligands like small molecules, biomolecules, surfactants, polymers, dendrimers, ^{66, 67}.
• The multivalent surface enables covalently or non-covalently conjugating multiple bioactive agents or biological macromolecules to achieve target-specific interaction and biocompatibility ⁶⁸.

Application of Smart Nanocarriers Dendrimer ^{69, 70, 71, 72}:

Biomedical Study: Dendrimers are extensively used in the biomedical field, where they're used as analogs to proteins, enzymes, and germicides where they're primarily used to concentrate the target cells and conjugate to the host dendrimeric cells, for representative, poly (amidoamine) dendrimer.

Magnetic Resonance: Dendrimers are considerably used in glamorous resonance to ameliorate the contrasts of the image. For representative, metallic dendrimers are used to produce the glamorous resonance imaging difference agent.

Biomimics: Dendrimers are also used to mimic the variety of biomolecules and produce the medium.

Solubility improvement: Dendrimers help perfect the solubility profile of poor and sparingly answerable medicines, resulting in increased bioavailability of medicines.

Dummy and Carrier for Formulations: Dendrimer particles have the capability to cross the cell membranes because of invariant size; due to this property, they help in colorful pharmacological conditioning.

Marketed Product available on the Dendrimers ^{73, 74, 75, 76}:

Advantages of Smart Nanocarriers ^{77, 78, 79, 80, 81}:

• Improves the solubility of poorly soluble drug
• Increases the stability of active ingredients within the cores.
• Uniform in size enhance their stability to the cross membrane and reduce the undesired clearance from the body.
• Presence of dynamic internal cavities where ions or internal molecules can be hosted.
• Targeted delivery is possible via targeting ligands conjugated to the dendrimer surface.
• Nanoparticles have many potential advantages, including increased strength and durability, improved electrical conductivity, and enhanced catalytic activity.
• Drug release in a controlled and sustained manner
• Less prone to bacterial resistance Can cross tissue barriers (e.g., blood-brain barrier) Extended therapeutic lifetime due to slow elimination Controlled drug release Broad therapeutic index Improved solubility Low immunosuppression.
• Incorporation of hydrophilic and hydrophobic drugs
• Tunable chemical and physical properties
• Use of a lot of biodegradable materials when desired
• Existence of pH, enzymatic, hydrolysis, etc., sensitive properties when preferred proper polymers
• Reproducible data when using synthetic polymers
• Higher stability than lipid-based ones.
• Act like a solubility enhancer.

Disadvantages of Smart Nanocarriers:

• Gathering of intravenously injected nanomaterials in tissues and organs high systemic exposure to locally administered drugs with proper doses for desirable therapeutic use high systemic exposure to locally administered drugs with proper doses for desirable therapeutic use Nanotoxicity (lung, kidney, liver, brain, germ cell, metabolic, etc.)
• Lack of characterization techniques that are not affected by the properties of nanoparticles (NPs).
• Difficulty with their scale-up
• Insufficient toxicological assessment in the literature
• Use only for lipophilic drug
• Low drug-loading capacity
• Dependency of critical micelle concentration
• Protecting drugs from environmental conditions
• Increasing solubility of highly lipophilic drugs
• Not a good candidate carrier for hydrophilic drugs
• Tunable chemical and physical properties

• Multiple functional groups for targeted drug delivery
• Cellular toxicity
• Elimination and metabolism depend on the generation and materials
• Covalently associating drugs
• Acting like solubility enhancers
• High cost for their synthesis

Why Dendrimer is Smart to Other Nanocarriers:

• Due to its nanoscale size, monodisperse nature, water solubility, bio-compatibility, and highly branched structure, it is highly interesting. Because of the nanoscale size, it can be used as a drug carrier.
• Dendrimers are three-dimensional, hyperbranched nanoparticles consisting of polymeric branching units covalently attached to a central core, organized in concentric layers (named generations), and terminate with several external surface functional groups.
• Dendrimers can increase the solubility and bioavailability of hydrophobic drugs that can be entrapped in their intramolecular cavity or conjugated to their surface functional groups.
• The branched structure makes the dendrimer versatile. Moreover, all of its active groups on the surface face outward, which results in a higher drug encapsulation rate.

CONCLUSION: Dendrimer provides a unique platform for medicine attachment that can bind and release medicines through several mechanisms. A dendrimer is a delivery vehicle for anticancer agents that are inadequately answerable in water and can promote the transport of medicines across natural membranes. Developing new smart accouterments and tracking their structural eventuality have been in focus for curing complaints and other operations similar as catalyzing biomolecules like proteins and pickyAPI Medicinal, poisonous essence, pigments, and germicides have been thrust areas of exploration in the field of accouterments and pharmaceutical lores. The multifunctional accouterments of multipurpose uses with several dendrimer branching have innumerable list spots and are in high demand for their medicine list, lading eventuality, and bio coatings. Dendrimers are among the rearmost generations of nano-systems that constitute implicit medicine carriers. Dendrimer chemistry is one of ultramodern chemistry's most witching and fleetly growing areas. In recent times Dendrimers have entered significant consideration as medicine delivery carriers. As a medicine delivery agent, Dendrimer is a promising, safe, and picky medicine delivery option.

ACKNOWLEDGMENTS: The authors thank the Institute of Pharmacy Bundelkhand University Jhansi Uttar Pradesh. To provide the facilities for compiling this review article.

CONFLICT OF INTEREST: The authors have no conflict of interest.

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    Suman, Saddam, Alok S and Prajapati RN: Dendrimers is a smart novel carrier in drug delivery: an insight. Int J Pharm Sci & Res 2023; 14(7): 3345-59. doi: 10.13040/IJPSR.0975-8232.14(7).3345-59.

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