Novel Drug Delivery Systems Research Articles

Nanotechnology Based Alternative For The Topical Delivery Of Psoriasis

Psoriasis, a chronic autoimmune disease, is characterized by patches of abnormal skin that are red, pink, or purple, dry, itchy, and scaly. It affects people of all ages, with peak onset between 32 and 52 years old. Psoriasis is classified into three main types: vulgaris, pustular, and inverse. Novel Drug Delivery Systems (NDDS) offer innovative approaches to deliver pharmaceutical substances to the body more effectively and safely. These systems aim to increase bioavailability, maintain therapeutic drug concentrations, and minimize toxicity. Several NDDS are being used for psoriasis treatment, including: • Topical nanoparticles: These offer enhanced skin penetration, controlled release, and reduced side effects. • Liposomes: Spherical vesicles that can encapsulate drugs and deliver them to targeted areas. • Microneedle systems: Create microchannels in the skin for improved drug penetration and localized delivery. • Transdermal patches: Provide non-invasive, sustained drug delivery. • Smart drug delivery systems: Respond to specific stimuli, enabling targeted and controlled drug release

Curcumin Nanostructured Drug Delivery Induces the Anti-cancer and Anti-inflammatory activity In Vitro and In Vivo

Background: The therapeutic potential of plant-derived pharmaceuticals is often limited by poor bioavailability and rapid metabolism. This study aims to enhance the pharmacological effects of curcumin, a bioactive compound from plants, through the development of novel drug delivery systems (NDDS). Methods: Various NDDS, including liposomes, nanoparticles, and microspheres, were formulated to encapsulate curcumin. We evaluated their drug release characteristics, encapsulation efficiency, and particle size in vitro. The pharmacological effectiveness of these formulations was assessed using cytotoxicity assays on human cancer cell lines and anti-inflammatory models in rats. Results: The liposomal formulation achieved an encapsulation efficiency of 85% with an average particle size of 150 nm. The nanoparticle and microsphere formulations demonstrated encapsulation efficiencies of 78% and 90%, with particle sizes of 200 nm and 10 µm, respectively. All formulations exhibited a sustained release profile, with 70% of curcumin released over 24 hours. Cytotoxicity studies revealed that the NDDS formulations significantly increased cell death in cancer cells, with the liposomal formulation showing a 50% increase in apoptosis. In vivo experiments indicated a 60% reduction in paw edema with the nanoparticle formulation compared to the control group, highlighting enhanced anti-inflammatory effects. Conclusion: The findings of this study suggest that NDDS significantly improve the encapsulation efficiency, sustained release, and pharmacological activity of curcumin. This approach demonstrates the potential of NDDS to enhance the clinical efficacy of plant-derived drugs, leading to improved therapeutic outcomes.

Novel Drug Delivery Systems: An effective platform for Enhanced Therapy

Modern developments in drug pharmacokinetic and Pharmacodynamics behavior make developing the optimal drug delivery method more rational. It is already clear that future success in medication delivery research will mostly come from interdisciplinary collaborations. Pharmaceutical businesses stand to gain enormous commercial potential and advance human disease treatment by employing better drug delivery methods to make therapeutic agents safer and more effective. It is already apparent that multidisciplinary efforts will mostly be responsible for future success in drug delivery research. Any therapeutic agent that can be made safer and more effective while using an enhanced drug delivery method represents a step forward in the treatment of human diseases as well as significant marketing potential for pharmaceutical companies. The best drug delivery systems, based on the etiology and physiological requirements of the body, deliver a predefined dose of medication to the intended site at the appropriate time and place. The speed at which a medication reaches its intended location cannot be controlled by conventional pharmaceutical dosage forms. Novel drug delivery systems (NDDS) are carriers that maintain the drug concentration in the therapeutic range for longer periods of time and may also deliver the content to the targeted site if desired and as needed, because higher doses often cause serious side effects during treatment. Because of this, therapeutic dosages for drug dispersion in non-target tissue and bodily fluids may be far higher than those needed in target cells.

Magnetic nanoparticles (MNPs): Design, characterization, release mechanism and remote-controlled application for targeted therapeutics

MNPs as novel drug delivery system (NDDS) approach possess several magnetic properties for targeted and controlled delivery in various biomedical application. Unlike normal nanoparticles, MNPs enable to respond to external magnetic fields, allowing for manipulation, guidance, and functionalisation within the body. This review encompasses a wide range of scientific and technological goals aimed in understanding their properties, synthesis methods, characterization techniques, surface functionalisation strategies and application. Drug delivery based on magnetic properties has advanced dramatically to enhance therapeutic bioavailability, stability, and targeted delivwery. Converting nanoparticles into MNPs involves introducing magnetic properties to the nanoparticles through core-shell structures, doping or coating with magnetic materials, physical or chemical reactions, or biological synthesis methods. However, this study demonstrates the versatility and potential of magnetic nanoparticles (MNPs) for various biomedical applications. Moreover, the in vitro and in vivo studies highlight MNPs' promising role in targeted drug delivery, imaging contrast enhancement, and magnetic hyperthermia for cancer therapy. Moving forward, further research is warranted to optimize MNPs' design, explore novel functionalization strategies, and address challenges related to biocompatibility, scalability, and regulatory approval. Therefore, MNPs reflects transformative impact across various fields, emphasizing their potential to drive advancements in healthcare, environmental protection, and technology. Continued research and innovation in this field are expected to unlock new opportunities and address global challenges, driving progress towards a healthier, cleaner, and more technologically advanced future.

Advancements in Novel Drug Delivery Systems: Techniques for Pre and Post Formulation Analysis

Novel drug delivery systems (NDDS) are revolutionizing treatment by leveraging progressive technologies to deliver drugs precisely to their targets within the body. This targeted approach enhances therapeutic efficacy while minimizing unwanted side effects. This review delves into the various techniques employed for developing and characterizing NDDS. We focus on the critical role of characterization, encompassing both pre- and post-formulation stages. Pre-formulation techniques explored include physicochemical properties (melting point, solubility, etc.) spectroscopic analysis (UV, FTIR), thermal analysis (DSC, TGA), and powder characterization (XRD, polarized microscopy). In addition, post-formulation methods such as NMR spectrometry, atomic force microscopy, and in vitro drug release investigations are covered. By comprehensively characterizing these systems, researchers can optimize their design and formulation, ultimately leading to improved patient outcomes and encouraging improvements in the study and development of pharmaceuticals.

Neuroprotective Role of Phytoconstituents-based Nanoemulsion for the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disorder (ND), affecting more than 44 million individuals globally as of 2023. It is characterized by cognitive dysfunction and an inability to perform daily activities. The progression of AD is associated with the accumulation of amyloid beta (Aβ), the formation of neurofibrillary tangles (NFT), increased oxidative stress, neuroinflammation, mitochondrial dysfunction, and endoplasmic reticulum stress. Presently, various phytomedicines and their bioactive compounds have been identified for their neuroprotective effects in reducing oxidative stress, alleviating neuroinflammation, and mitigating the accumulation of Aβ and acetylcholinesterase enzymes in the hippocampus and cerebral cortex regions of the brain. However, despite demonstrating promising anti-Alzheimer's effects, the clinical utilization of phytoconstituents remains limited in scope. The key factor contributing to this limitation is the challenges inherent in traditional drug delivery systems, which impede their effectiveness and efficiency. These difficulties encompass insufficient drug targeting, restricted drug solubility and stability, brief duration of action, and a lack of control over drug release. Consequently, these constraints result in diminished bioavailability and insufficient permeability across the blood-brain barrier (BBB). In response to these challenges, novel drug delivery systems (NDDS) founded on nanoformulations have emerged as a hopeful strategy to augment the bioavailability and BBB permeability of bioactive compounds with poor solubility. Among these systems, nanoemulsion (NE) have been extensively investigated for their potential in targeting AD. NE offers several advantages, such as ease of preparation, high drug loading, and high stability. Due to their nanosize droplets, NE also improves gut and BBB permeability leading to enhanced permeability of the drug in systemic circulation and the brain. Various studies have reported the testing of NE-based phytoconstituents and their bioactives in different animal species, including transgenic, Wistar, and Sprague-Dawley (SD) rats, as well as mice. However, transgenic mice are commonly employed in AD research to analyze the effects of Aβ. In this review, various aspects such as the neuroprotective role of various phytoconstituents, the challenges associated with conventional drug delivery, and the need for NDDS, particularly NE, are discussed. Various studies involving phytoconstituent-based NE for the treatment of AD are also discussed.

A Brief Review on the Current Trends in Microencapsulation

Microencapsulation has emerged as a pivotal technology in the field of novel drug delivery systems (NDDS), offering significant advantages in enhancing the efficacy, safety, and patient compliance of therapeutic agents. This cutting-edge technique involves encapsulating active pharmaceutical ingredients (APIs) within microscopic protective coatings, enabling controlled release, targeted delivery, and improved bioavailability. Microencapsulation has proven to be a versatile tool in addressing various pharmaceutical challenges, such as masking unpleasant tastes, protecting sensitive drugs from degradation, and modifying the absorption site of drugs. This comprehensive review aims to provide an in-depth understanding of microencapsulation, its principles, techniques, and diverse applications in the pharmaceutical industry. The article delves into the reasons for employing microencapsulation, including extended or sustained drug release, taste and odor masking, conversion of liquids into free-flowing powders, and stabilization of light, moisture, or oxygen-sensitive drugs. Additionally, the classification of microparticles based on their core and shell materials is discussed. Furthermore, the review explores the advantages and disadvantages of microencapsulation, highlighting its ability to protect encapsulated active agents, transform gases and liquids into solid particles, modify surface and colloidal properties, and alter the release profiles of drugs. Various microencapsulation techniques are extensively covered, including air suspension, coacervation phase separation, pan coating, spray drying and spray congealing, and solvent evaporation. The applications of microencapsulation span across diverse industries, such as pharmaceuticals, cosmetics, agrochemicals, and food. This review provides insights into the utilization of microencapsulated products in these sectors, emphasizing their role in enhancing product functionality, stability, and controlled release

Preparation and Characterization of Liposomes in Novel Drug Delivery Systems: A Review

Liposomes have emerged as versatile drug delivery vehicles with the potential to improve the therapeutic efficacy and safety profiles of various drugs. These lipid-based vesicles offer advantages such as biocompatibility, versatility in encapsulating hydrophilic and hydrophobic drugs, and the ability to target specific tissues or cells. This review provides a detailed examination of the preparation and characterization methods of liposomes in novel drug delivery systems (NDDS). It covers various techniques for liposome preparation, including conventional methods and advanced approaches, as well as the characterization parameters essential for evaluating liposomal formulations. Additionally, recent advancements, challenges, and future directions in the field are discussed.

Application of 32 factorial design for loratadine-loaded nanosponge in topical gel formulation: comprehensive in-vitro and ex vivo evaluations.

Loratadine (LoR) is a highly lipophilic and practically insoluble in water, hence having a low oral bioavailability. As it is formulated as topical gel, it competitively binds with the receptors, thus reducing the side-effects. The objective of this study was to prepare LoR loaded nanosponge (LoR-NS) in gel for topical delivery. Nine different formulations of emulsion were prepared by solvent evaporation method with polyvinyl alcohol (PVA), ethyl cellulose (EC), and dichloromethane (DCM). Based on 32 Full Factorial Design (FFD), optimization was carried out by varying the concentration of LOR:EC ratio and stirring rate. The preparations were subjected for the evaluation of particle size (PS), in vitro release, zeta potential (ZP) and entrapment efficiency (EE). The results revealed that the NS dispersion was nanosized with sustained release profiles and significant PS. The optimised formulation was formulated and incorporated into carbopol 934P hydrogel. The formulation was then examined to surface morphological characterizations using scanning electron microscopy (SEM) which depicted spherical NS. Stability studies, undertaken for 2months at 40 ± 2°C/75 ± 5% RH, concluded to the stability of the formulation. The formulation did not cause skin irritation. Therefore, the prepared NS hydrogel proved to be a promising applicant for LoR as a novel drug delivery system (NDDS) for safe, sustained and controlled topical application.

Nanotechnology in Herbal Drug Delivery Systems: Enhancing Therapeutic Efficacy and patient compliance

Herbal medicines have been widely used throughout history, and due to their decreased possibility of adverse effects when compared to modern drugs, both medical professionals and patients have recognized their superior therapeutic efficacy. A systematic strategy for delivering the elements over time is necessary for phytotherapeutics in order to maximizeadherence of patients and prevent repetitive administration. This might be accomplished by creating novel drug delivery systems (NDDSs) for herbal components. Through lowering toxicity and raising bioavailability, NDDSs contribute to increasing therapeutic efficacy by reducing the need for successive administrations to address non-compliance. Nanosized herbal medication delivery techniques may one day enhance performance and address problems with plant-based medicines. To fight other chronic illnesses, such as diabetes, cancer, and others, the conventional medical system must deploy nanocarriers as an NDDS. The article covers the numerous nano herbal drugs and nano herbal cosmetics currently available on the market, as well as the characteristics, benefits, and drawbacks of nano drug delivery systems.

An Updated Comprehensive Review on Novel Drug Delivery Systems (NDDS) In the Pharmaceuticals

The field of pharmaceutical sciences has witnessed a paradigm shift with the advent of Novel Drug Delivery Systems (NDDS), which aim to enhance therapeutic efficacy, reduce side effects, and improve patient compliance. This comprehensive review explores the latest advancements and innovations in NDDS, encompassing a diverse range of delivery platforms and strategies.(NDDs are transforming the landscape of pharmaceutical treatment, offering unparalleled potential for enhanced therapeutic efficacy, improved bioavailability, controlled release, targeted delivery, and enhanced stability. This comprehensive review explores the diverse landscape of NDDS, highlighting recent advancements and addressing key challenges. Prominent NDDS include liposomes, nanoparticles, micelles, polymeric drug conjugates, monoclonal antibodies, implants, and patches. Each system possesses unique properties and applications, tailored to specific drugs and therapeutic needs. Recent breakthroughs in targeted nanocarriers, gene therapy vectors, and 3D-printed personalized dosage forms are pushing the boundaries of innovation. The main highlights of the present review firstly the basics on NDDs, the several approaches of nano drug carriers for the drug delivery with their preparation methods and example. The middle version of review discuss the recent advancements techniques in the preparation of NDDs carriers and lastly the marketed formulation of particular drug carrier.

Recent Updates on the Therapeutics Benefits, Clinical Trials, and Novel Delivery Systems of Chlorogenic Acid for the Management of Diseases with a Special Emphasis on Ulcerative Colitis.

Ulcerative colitis (UC) is a multifactorial disorder of the large intestine, especially the colon, and has become a challenge globally. Allopathic medicines are primarily available for the treatment and prevention of UC. However, their uses are limited due to several side effects. Hence, an alternative therapy is of utmost importance in this regard. Herbal medicines are considered safe and effective for managing human health problems. Chlorogenic acid (CGA), the herbal-derived bioactive, has been reported for pharmacological effects like antiinflammatory, immunomodulatory, antimicrobial, hepatoprotective, antioxidant, anticancer, etc. This review aims to understand the antiinflammatory and chemopreventive potential of CGA against UC. Apart from its excellent therapeutic potential, it has been associated with low absorption and poor oral bioavailability. In this context, colon-specific novel drug delivery systems (NDDS)are pioneering to overcome these problems. The pertinent literature was compiled from a thorough search on various databases such as ScienceDirect, PubMed, Google Scholar, etc., utilizing numerous keywords, including ulcerative colitis, herbal drugs, CGA, pharmacological activities, mechanism of actions, nanoformulations, clinical updates, and many others. Relevant publications accessed till now were chosen, whereas non-relevant papers, unpublished data, and non-original articles were excluded. The present review comprises recent studies on pharmacological activities and novel drug delivery systems of CGA for managing UC. In addition, the clinical trials of CGA against UC have been discussed.

Formulation and Evaluation of Phytosomes of Pterocarpus santalinus Extract

Abstract: Novel drug delivery system (NDDS) phytosomes were prepared by complexing phospholipids: Cholesterol and Leaves extract of Pterocarpus santalinus can act as molecular adhesive to bind components together. Their ability to penetrate lipid-rich biomembranes and shield the essential components of the herbal extract from being destroyed by digestive secretions and gut bacteria increases bioavailability. The bioavailability of the herbal formulation is increased by phytosomes' ability to distribute the standardised plant extracts and phytoconstituents through different routes of drug administration methods. The present study directed toward the development and evaluation of phytosomes of Pterocarpus santalinus. Through an in-vitro dissolution study, the produced complex's physicochemical characteristics were examined. The outcome demonstrated that there was no formation of a novel chemical between the hydroalcoholic extract and the phospholipids in the Methanolic extract-phospholipid complex. Prepared Pterocarpus santalinus extract phytosomes showed better bioavailability.

Current reviews depicting therapeutic potential of novel drug delivery system in rheumatoid arthritis

Modern advancement in science and technology has altered the way we detect, treat and prevent different diseases in all aspects of human life. Rheumatoid Arthritis (RA) is chronic progressive autoimmune disease in which body’s immune system has role to protect the health by attacking foreign bacteria but the virus mistakenly attacking the joints as a result thickened synovium, pannus formation, & destruction of bone, cartilage occurs. Researchers are still researching but are unable to know the exact reason for the disease. Although, it is believed that genes and environmental factors play an important role in the development of RA. In this review the pathophysiology, predictors and factors involved in pathogenesis of RA have been investigated. The conventional drug therapeutic agents and emerging novel drug delivery system (NDDS) like nanoparticles, dendrimers, micelles, microspheres, liposomes and so on are discussed, as these are the tools which show promising effect in overcoming the limitations associated with conventional drug delivery systems. Although several NDDS have been used for various purposes, liposomes have been focused and found to have its potential applications in RA diagnosis and therapy. In addition, the therapeutic effectiveness, and challenges for RA by using these novel drug delivery systems have been reviewed along with its future perspectives.

Preparation of Allium Cepa Peel Extract-mediated Silver Nanoparticles: A Hair Dye Formulation.

The burgeoning field of nanotechnology has ushered in innovative Novel drug delivery systems (NDDS) that enhance the efficacy, safety, and patient compliance of pharmaceutical treatments. This study explores the synthesis and application of silver nanoparticles (AgNPs) using green chemistry approaches, specifically leveraging plant extracts as reducing agents. AgNPs, known for their unique physical and chemical properties, including antimicrobial capabilities, offer significant potential in modern drug delivery. This study investigates the potential of using Allium cepa peel waste for the green synthesis of silver nanoparticles. This study also revealed the resultant formation of silver nanoparticles through microscopy and UV spectroscopy, which were further analyzed by Scanning Electron Microscopy. This green synthesis method not only aligns with environmentally friendly practices but also provides a cost-effective and scalable approach to nanoparticle production. We formulated a hair dye incorporating these AgNPs and evaluated its physicochemical parameters, demonstrating enhanced performance compared to control formulations without nanoparticles. This work underscores the promise of green-synthesized nanoparticles in developing advanced drug delivery systems, offering insights into future applications in anticancer and antimicrobial treatments. Our findings advocate for the broader adoption of sustainable nanotechnology in pharmaceutical sciences, potentially revolutionizing the treatment landscape with safer and more effective therapeutic options.

A review on nano emulsions in Novel Drug Delivery Systems (NDDS)

A review on nano emulsions in Novel Drug Delivery Systems (NDDS)

Novel Drug Delivery System: Brief Review

Current developments in our knowledge of the pharmacokinetic and pharmacodynamics behaviour of drugs provide a more logical framework for designing the best possible drug delivery system. It is understandable that multidisciplinary efforts will play a major role in the success of drug delivery research in the future. Any therapeutic agent that has the potential to be safer, more effective, and use an enhanced drug delivery mechanism offers pharmaceutical companies significant marketing prospects as well as advancements in the treatment of illnesses. Since ancient times, humans have utilized plants as food and medicine, viewing them as nature's solutions. The underlying idea is that every sickness has a remedy that is concealed in better ways using ayurvedic, homeopathic and allopathic. However, in order to promote sustained release, improve patient compliance, etc., the way herbal medications are delivered must also be modified. Because of challenges with processing, standardizing, extracting, and identifying them, herbal medications had historically been unable to draw scientists' attention to the development of novel drug delivery methods. However, with today's technological advancements, the development of herbal revolutionary drug delivery systems is made possible by novel drug delivery systems (NDDS). It is possible to achieve protection against toxicity, stability enhancement, enhanced bioavailability, and protection against chemical and physical degradation of herbal formulations through the application of advanced procedures which must give the result in better or faster way. In this review we will get the method of preparations of NDDS and the Application of NDDS.
 Keywords: Herbal Drugs, Enhanced drug delivery, Phytosomes, Nanoparticles, liposomes.

Classical and Modern Review on Sneha Kalpana w.s.r to Ghrita Kalpana

Ayurvedic dosage forms hold a unique place in pharmaceutics and therapeutics. Sneha Kalpana is a group of products of medicated Taila and ghee. It is an Ayurvedic preparation of oleaginous medicine that is prepared with the use of Kalka (herbal paste of different parts of plants), Kwatha (specifically prepared decoction in accordance with Ayurvedic principles) or Drava Dravya (any other liquid such as milk, juices etc.) With suitable Sneha as base taken in specific proportion, both the ingredients are mixed and heated under a specific temperature to meet the desired therapeutic requirement. In the modern terminology, Sneha can be correlated with Lipids. Materials and Methods: Literature related to Sneha Kalpana and Lipids have been referred from various Ayurvedic texts, modern medical books, research papers and journals. Properties of Sneha Dravya, Sneha sources, phases of Sneha Kalpana, effect of Sneha Paka on therapeutics, Sneha dose, Anupana, shelf-life, lipids and their types have been explained and compiled from different sources. Conclusion: Sneha Kalpana is used to extract fat soluble active principles from drugs and also to increase permeability of drugs so that they can be absorbed easily through the cell membrane. It is the only dosage form that can be administered through all routes of body, viz., Nasya (nasal route), Tarpan (ocular route), Karnapooran (auditory route), Snehapan (oral route), Abhyanga (topical route), Basti (vaginal, urethral, anal route). In the Modern era, various dosage forms can be developed as novel drug delivery system (NDDS) utilizing the concept of Sneha Kalpana (Lipids) to increase the bio availability of drugs to show maximum therapeutic effect.

Solid Lipid Nanoparticles: Peculiar Strategy to Deliver Bio-Proactive Molecules.

Novel Drug Delivery Systems (NDDS) provide numerous benefits compared to conventional dosage forms. Poor aqueous solubility, low bioavailability, frequent dosing, and particular hydrophilic lipophilic character of the drug are the biological factors associated with the traditional systems leading to the development of SLNs. For improving the solubility profile, enhancing the bioavailability, and attaining the best possible therapeutic effect of lipid inclined or aqueous inclined drug, formulating solid lipid nanoparticles is the best choice. Solid Lipid Nanoparticles (SLNs) have been projected as a colloidal carrier system with a size of 50-1,000 nm, collectively combining the benefits of other colloidal systems like liposomes, emulsions, etc., for delivering the drug at the target site. High absorption, high stability, and efficient drug packing enhance the pharmacokinetic and pharmacodynamic properties of the packed drug. Solid Lipid Nanoparticles can be developed in different dosage forms and administered via routes such as nasal, rectal, oral, topical, vaginal, ocular, and parenteral. They have higher physicochemical stability and the batch size can be easily scaled up at a low cost. Lipophilic as well as hydrophilic drugs can be easily incorporated into solid lipid nanoparticles. In this manuscript, the authors have reviewed different aspects of solid lipid nanoparticles, major principles behind mechanism methods, recent patents, applications, and therapeutic potentials of solid lipid nanoparticles.

Implantable Drug Delivery System: An Innovative Approach

The conventional routes of drug administration has limited control over drug release and maintaining constant plasma therapeutic drug concentrations for longer periods of time. To avoid these problems associated with utilization of traditional dosage forms, there was essential need for development of new dosage forms which would discharge drugs at controlled rate for local activity. This led to improvement of Novel Drug Delivery Systems (NDDS) that offers optimisation of therapeutic properties of drugs and makes them safer, productive and dependable over traditional ways of administration. Implantable drug delivery system (IDDS) forms a part of novel drug delivery system. This route of administering medications allows targeted distribution, location specificity, constant release rate, low amount of drug requirements, and minimisation of adverse effects with improved efficacy. It provides possibility of administering drugs once weekly to yearly which otherwise previously require frequent daily dosing. Different implantable technologies are currently in use for many therapeutic applications such as in dentistry, ophthalmology, contraception and oncology. However, the expensiveness of this newly improved drug delivery system is quite high which hinders its large scale use. Moreover, the recently developed devices require further enhancement and hence thorough scientific trials are needed before wide implementation in populations.
 Keywords: Implantable drug delivery, implants, drug delivery system, implantable pump, modulated drug delivery, novel drug delivery system