Role of Modular in Effective Drug Delivery System: A Review

Sofiya Verma, Deepak Jain*, Shashi Bharti Shukla, Priyanka Yadav, Nisha Sonkar and Joy Ashish Soloman

Shri Ram Institute of Technology, Jabalpur (MP)

ABSTRACT:

To achieve minimal side effect by maximum therapeutic effect a modular system provide an effective way to deliver the therapeutic agents to biological tissue includes a surgically implantable lead configured to be inserted into the biological tissue. There are also two aspects to creating an effective drug, finding a chemical compound that has the desired biological effect and minimal side-effects and then delivering it to the right place in the body for it to do its job. This drug delivery are very novel and versatile and can be adapted to delivery of multi-functional drug ,proteins, peptides, DNA and smaller chemical compounds like most drugs. Idea deliveries of drug with modular along with carrier provide an advantageous way in the drug delivery system. The various significant roles of modular using carriers like nanoparticles, liposome, microspheres etc for targeting drug into the desired site of biological tissue have been discussed in this paper. The breadth of applications makes the technology very powerful for achieving their goal in targeting drug in controlled manner without or minimal side effect.

KEYWORDS: Modular, Therapeutic, Controlled, Side-Effect.

INTRODUCTION:

An ideal controlled drug delivery system is the one which deliver the drug at a predetermine rate, locally or systemically for a specified period of time. Thus the chief objective of most product should we controlled delivery to reduce dosing frequency to an extent that daily dose is sufficient management.^1.2,3,6,7

The basis rationale of a controlled drug delivery system is to optimize the biopharmaceutics, pharmacokinetic and pharmacodynamic properties of a drug in such a way that its utility is maximized through reduction in side effects and cure or control of condition in the shortest possible time by using smallest quantity of drug, administered by the most suitable route. There are also two aspects to creating an effective drug, finding a chemical compound that has the desired biological effect and minimal side-effects and then delivering it to the right place in the body for it to do its job.^1-5

A modular system for delivering therapeutic agents to biological tissue includes a surgically implantable lead configured to be inserted into the biological tissue is new outcome to enhance the effectiveness and reduce undesirable side-effects of a number of different drugs. This drug delivery are very novel and versatile and can be adapted to delivery of multi-functional drug ,proteins, peptides, DNA and smaller chemical compounds like most drugs. The breadth of applications makes her technology very powerful. . The different modules of the transporters, which are highly expressed and easily purified to retain full activity of each of the modules, are interchangeable, meaning that they can be tailored for particular applications.^8,9,10

VARIOUS APPROACHES OF MODULAR IN DRUG DELIVERY SYSTEM:

Modular in Nanoparticle Drug Delivery System:^12,14,15,17

A modular, multi-functional drug delivery system that promises simultaneously to enhance the effectiveness and reduce undesirable side-effects of a number of different drugs.when attached to the nanosponge, carries it and its cargo across biological barriers into specific intracellular compartments, which are very difficult places for most drugs to reach. For this method drug delivery are very novel and versatile and can be adapted to delivery of proteins, peptides, DNA and smaller chemical compounds like most drugs. The breadth of applications makes her technology very powerful.

A self-assembled, modular DNA delivery system mediated by silica nanoparticles:^11,13,15,16

Due to the growing concerns over the toxicity and immunogenicity of viral DNA delivery systems, DNA delivery via non-viral routes has become more desirable and advantageous. The ideal non-viral DNA delivery system should be a synthetic system that mimics viral vectors. It should also be biocompatible, efficient, and modular so that it is tunable to various applications in both research and clinical settings. The first successful step towards this modular synthetic DNA delivery system is demonstrated: a three-component transfection system mediated by silica nanoparticles. Dense silica nanoparticles serve as an uptake-enhancing component by physical concentration at the cell surface; enhanced transfection due to the particles is seen with almost every transfection reagent tested with little toxicity. In addition, a mathematical model has been built that successfully predicts several important parameters of transfection enhancement. This three-component transfection system lays the groundwork for a future multi-component modular synthetic.

Cellular fate of a modular DNA delivery system mediated by silica nanoparticles:^18-21

Development of efficient molecular medicines, including gene therapeutics, RNA therapeutics, and DNA vaccines, depends on efficient means of transfer of DNA or RNA into the cell. Potential problems, including toxicity and immunogenicity, surrounding viral methods of DNA delivery have necessitated the use of nonviral, synthetic carriers. To better design synthetic carriers, or transfection reagents, the modular design of viruses has inspired a modular approach to DNA and RNA delivery. Each modular component can be designed to circumvent each of the many barriers. The modular approach will allow modification of individual components for a specific application. By utilizing a dense silica nanoparticle to form a ternary complex, transfection efficiency of a DNA-transfection reagent complex was increased by a factor of approximately 10 by concentrating the DNA at the surface of cells. Surface modification of the silica nanoparticles allowed determination of the cellular uptake mechanism with only minor alteration of transfection efficiency²¹,. Nanoparticles are internalized by an endosome-lysosomal route followed by perinuclear accumulation. The modification mechanism confirms that surface modification of the modular system can allow specific moieties to be incorporated into the modular system without significant alteration of the transfection efficiency. By showing that the modular system based upon concentration of DNA at the level of the cell can be used to increase transfection efficiency, we have shown that further modification of the system may better target DNA delivery and overcome other barriers of DNA expression.

Use of modular drug delivery system for minimizing trauma during and after insertion of a cochlear lead:^23-25,28

A system for delivering therapeutic agents to biological tissue includes a surgically implantable lead configured to be inserted into the biological tissue, the surgically implantable lead including a preformed cavity; and a modular capsule containing a therapeutic agent which includes dexamethasone base; the modular capsule being secured within the preformed cavity; the modular capsule releasing the therapeutic agent into the biological tissue. A method of delivering therapeutic agents to biological tissue includes obtaining a surgically implantable lead with a preformed cavity; obtaining a modular capsule containing a therapeutic agent comprising dexamethasone base and securing it within the preformed cavity; and inserting the surgically implantable lead into the biological tissue.

Targeting cancer cells by novel engineered modular transporters system:^28-30

A major problem in the treatment of cancer is the specific targeting of drugs to these abnormal cells. Ideally, such a drug should act over short distances to minimize damage to healthy cells and target subcellular compartments that have the highest sensitivity to the drug. Thus using modular recombinant transporters to target photosensitizers to the nucleus, where their action is most pronounced, of cancer cells overexpressing ErbB1 receptors. By producing a new generation of the transporters consisting of (a) epidermal growth factor as the internalizable ligand module to ErbB1 receptors, (b) the optimized nuclear localization sequence of SV40 large T-antigen, (c) a translocation domain of diphtheria toxin as an endosomolytic module, and (d) the Escherichia coli hemoglobin-like protein HMP as a carrier module. The modules retained their functions within the transporter chimera: they showed high-affinity interactions with ErbB1 receptors and α/β-importin dimers and formed holes in lipid bilayers at endosomal pH. A photosensitizer conjugated with the transporter produced singlet oxygen and ^·OH radicals similar to the free photosensitizer. Photosensitizers-transporter conjugates have >3,000 times greater efficacy than free photosensitizers for target cells and were not photocytotoxic at these concentrations for cells expressing a few ErbB1 receptors per cell, in contrast to free photosensitizers. The different modules of the transporters, which are highly expressed and easily purified to retain full activity of each of the modules, are interchangeable, meaning that they can be tailored for particular applications.

Future directions of liposome and immunoliposome-based cancer therapeutics:²⁹

The modular organization of immunoliposome technology enables a combinatorial approach in which a repertoire of monoclonal antibody fragments can be used in conjunction with a series of liposomal drugs to yield a new generation of molecularly targeted agents.

Gastric retention system for controlled drug release:^22,26,27,²⁹

An oral drug delivery system having delayed gastrointestinal transit comprising a non-continuous compressible element and an attached controlled release device and which in the expanded form resists gastrointestinal transit; and a modular system for use therein comprising a non-continuous compressible element and an attached receptacle means for receiving and holding a drug-containing orally administrable controlled release device and which in the expanded form resists gastric transit.

Modular approach in multifunctional Nanoparticle for integrated drug delivery, targeted and, diagnostics: synthetic method and practical application.

In particular, using gold colloids as a model system, block copolymer-stabilized composite nanoparticles (CNPs) were prepared via Flash NanoPrecipitation. Parameters controlling physical properties of the particles were identified experimentally and compared to predictions from a model of CNP formation in the diffusion-limited colloid aggregation regime. In addition, the combined incorporation of nanocrystals with drugs into a single construct was also demonstrated, enabling simultaneous drug delivery and medical imaging. In all cases, uniform particles were produced with tunable sizes between 75 nm and 275 nm, narrow particle size distributions, high encapsulation efficiencies, independently specified component compositions, and long term stability.

Recombinant modular transporters for cell-specific nuclear delivery of locally acting drugs enhance photosensitizer activity.^30-33

To deliver locally acting drugs such as photo sensitizers (PSs), describing modular recombinant transporters (MRTs) that are capable of targeting drugs not only to specific cells, but also to the most sensitive sub cellular compartment for the action of the drug, thus increasing both the drug efficacy and specificity of its effects. We designed gene modules encoding the corresponding polypeptide modules according to the scheme: BamHI site–module sequence–BglII site–stop codon–HindIII site. This structure allowed all gene modules to be placed at any position along the hybrid gene since the flanking BamHI and BglII restriction sites have identical sticky ends. -Melanocyte-stimulating hormone (MSH) was chosen as a ligand module conferring recognition and uptake by specific target cells (melanoma) through binding to and subsequent internalization mediated by overexpressed melanocortin receptors. The optimized SV40 T antigen (T-ag) nuclear targeting module had the sequence: Ser-Ser-Asp-Asp-Glu-Ala-Thr-Ala-Asp-Ala-Gln-His-Ala-Ala¹²⁴-Pro-Pro-Lys-Lys¹²⁸-Lys-Arg-Lys-Val-Glu-Asp-Pro¹³⁵, where the numbers refer to the T-ag amino acid sequence, with the nuclear localization sequence (NLS; residues 126–132) underlined. It is recognized with high affinity by the importin /ß heterodimer that, in concert with other transport factors, mediates import into the nucleus. The endosomolytic modules used were either the 1) GALA peptide shown to make pores in membranes at acidic pH or 2) translocation domain of diphtheria toxin together with its natural spacer (DTox), capable of permeating endocytotic membranes at acidic pH when in supramolecular complexes. Thus, we generated plasmids encoding a number of MRTs, including pR522 (HMP-NLS-MSH), pR523 (GALA-HMP-NLS-MSH), and pR676 (DTox-HMP-NLS-MSH), where HMP is a hemoglobin-like protein from Escherichia coli that functions as a carrier for PSs. The extent of MRT expression ranged from 5–8% of total protein for construct pR523 to 20–30% for constructs pR522 and pR676, with 60–70% solubility. The MRTs were purified on blue Sepharose, the single-step purification providing 90–95% purity.

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Received on 16.09.2010

Accepted on 12.10.2010

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Research Journal of Pharmaceutical Dosage Forms and Technology. 2(6): Nov.-Dec. 2010, 370-373