Exploring Drug Delivery to the Peritoneum


Book Description

The Peritoneal cavity (PC) is the key metastatic site for intra-abdominal malignancies (e.g., GI tract and rectal cancer). PC sites can be used to target several other diseases where lymphatic drug delivery is desired without dumping large amounts of the drug. Till recently, it was thought that treatment with curative intent was impossible but that was challenged by the introduction of cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC), and PIPAC (pressurized intraperitoneal aerosol chemotherapy). Recently, a growing number of preclinical and clinical studies advocate intraperitoneal (IP) chemotherapy as an alternative post-operative therapy for cancer. Although their effectiveness has been proven both experimentally and clinically, there is still little understanding of the role of drug delivery systems (DDS) in targeting drugs in the intraperitoneal (IP) cavity. There are two main challenges one posed by IP cavity where the residence time of a small molecular weight drug (20 kDa) is not sufficiently long to maintain therapeutic effect. This leads to frequent or continuous dosing. Another challenge is device-related or catheter-related problems, such as catheter obstruction, increased risk of infection, and bowel complications. Overall literature shows that the IP site is satisfactorily explored by clinicians but in terms of drug delivery not that much. One can see a clear-cut gap of expertise exchange between the two fields and guidelines from regulatory lawmakers on new medications./ppbr/ppIn summary, challenges like delivery to IP cavity, tumor or organ-specific targeting, efficient tissue penetration, optimal cellular uptake and intracellular residence of a drug, biocompatibility, toxicity, etc can be easily solved by smartly designing functional drug delivery systems (both nano and micro). Nanotechnologies have always fascinated humans for several decades and are now widely explored in the biomedical field. Diverse types of nanoparticles are being explored around the world, some examples include biodegradable nanoparticles, green nanoparticles, polymeric nanoparticles, lipid nanoparticles, metal nanoparticles, graphene, carbon nanotubes, and several others. Now a day's nanoparticles are gaining interest for drug targeting of chemotherapeutic drugs, immunotherapy, and gene delivery. Whereas microparticles can be explored for delayed drug delivery to the peritoneal cavity due to relatively slow removal from IP fluid. Hydrogels or other adhesive drug delivery may help to enhance peritoneal adhesions; thereby maintaining the balance between benefit and risk. Overall, drug delivery systems are key in IP targeting. That means drug delivery specialist and clinician needs to be connected to get the best out of this route of drug administration./ppbr/ppThe present book is a link between pharmaceutical scientists (drug formulators), clinicians, toxicologists, and regulatory experts. This book also provides a new perspective to researchers to divert or guide their research in an optimal way. Exploring Drug Delivery to the Peritoneum serves as a platform for upcoming technologies especially in the medical devices sector to face up and show potential in delivering drugs. It is a chance for commercial partners like insurance companies and the pharma industry to explore this direction./pp/pp




Drug Delivery Systems: Advanced Technologies Potentially Applicable in Personalised Treatment


Book Description

This book is part of a series dedicated to recent advances on preventive, predictive and personalised medicine (PPPM). It focuses on the theme of “Drug delivery systems: advanced technologies potentially applicable in personalised treatments”. The critical topics involving the development and preparation of effective drug delivery systems, such as: polymers available, self-assembly, nanotechnology, pharmaceutical formulations, three dimensional structures, molecular modeling, tailor-made solutions and technological tendencies, are carefully discussed. The understanding of these areas constitutes a paramount route to establish personalised and effective solutions for specific diseases and individuals.




PIPAC


Book Description

Peritoneal dissemination is a common route of cancer metastasis. The benefit of administering chemotherapy directly into the peritoneal cavity is supported by preclinical and pharmacokinetic data. In comparison to intravenous (IV) treatment, intraperitoneal (IP) administration results in a several-fold increase in drug concentration within the abdominal cavity. There is now growing evidence from clinical studies showing a survival advantage for IP chemotherapy in various tumor typies, including ovarian, gastric and colorectal cancer. However, while the use of IP chemotherapy is slowly gaining acceptance, it is not universal, largely due to the greater toxicity associated with this approach. Moreover, efficacy of IP chemotherapy is limited by poor distribution within the abdominal cavity and by poor tissue penetration. A new way of IP chemotherapy is the application of cytotoxics in form of a pressurized aerosol into the abdominal of thoracic cavity. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is applied through laparoscopic access using two balloon trocars in an operating room equipped with laminar air-flow. In a first step,a normothermic capnoperitoneum is established with a pressure of 12 mmHg. A cytotoxic solution (about 10% of a normal systemic dose) is nebulized with a micropump into the abdominal cavity, and maintained for 30 min. The aerosol is then removed through a closed suction system. Applying an aerosol in the peritoneal cavity allows a homogeneous distribution of the chemotherapeutic agent within the abdomen. Furthermore, an artificial pressure gradient is generated that overcomes tumoral interstitial fluid pressure, an obstacle in cancer therapy. This results in a higher local drug concentration compared to conventional IP or IV chemotherapy. At the same time the plasma concentration of the chemotherapeutic agent remains low. In first clinical studies with limited number of patients in ovarian, gastric and colorectal cancer, as well as peritoneal mesothelioma, PIPAC has obtained encouraging tumor response rates and survival, with a low-side effects profile. Larger clinical trials are currently ongoing to examine if these data can be reproduced and extrapolated to other situations.




Management of Peritoneal Surface Malignancies. (Cytoreductive Surgery, HIPEC, PIPAC, and Beyond)


Book Description

Peritoneal surface malignancies (PSM) include a heterogeneous group of primary tumors, like peritoneal mesothelioma, and peritoneal metastases from various origins such as ovarian, gastric, colorectal, or appendicular cancers. Their pathophysiology is complex and still not fully elucidated. Historically, due to their dismal prognosis, peritoneal surface malignancies were considered a terminal condition and treated as such in palliative intent.. Surgery has become pivotal in the treatment of PSM and the development of specific techniques of cytoreductive surgery (peritonectomies, “en-bloc” resection) open up a new era of curative intent treatments.




Peritoneal Carcinomatosis: A Multidisciplinary Approach


Book Description

This is the first volume to provide a multidisciplinary approach to peritoneal carcinomatosis encompassing molecular mechanisms, histopathology, regional and systemic cytotoxic therapy, and surgical options. Illustrations aid the reader throughout in the many facets of this disease. The book will be of particular interest for medical, surgical and gynecological oncologists faced with the complexities of decision making in patients suffering from PC.




Meyler's Side Effects of Drugs


Book Description

Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions, Sixteenth Edition, Seven Volume Set builds on the success of the 15 previous editions, providing an extensively reorganized and expanded resource that now comprises more than 1,500 individual drug articles with the most complete coverage of adverse reactions and interactions found anywhere. Each article contains detailed and authoritative information about the adverse effects of each drug, with comprehensive references to the primary literature, making this a must–have reference work for any academic or medical library, pharmacologist, regulatory organization, hospital dispensary, or pharmaceutical company. The online version of the book provides an unparalleled depth of coverage and functionality by offering convenient desktop access and enhanced features such as increased searchability, extensive internal cross-linking, and fully downloadable and printable full-text, HTML or PDF articles. Enhanced encyclopedic format with drug monographs now organized alphabetically Completely expanded coverage of each drug, with more than 1,500 drug articles and information on adverse reactions and interactions Clearer, systematic organization of information for easier reading, including case histories to provide perspective on each listing Extensive bibliography with over 40,000 references A must–have reference work for any academic or medical library, pharmacologist, regulatory organization, hospital dispensary, or pharmaceutical company




Emerging Nanotechnologies in Immunology


Book Description

Emerging Nanotechnologies in Immunology aims to deliver a systematic and comprehensive review of data concerning the nature of interaction and nano-related risks between the nanophamaceuticals currently in the pipeline of S&T development for skin, ocular, and nasal drug delivery, including absorption, toxicity, and the ability to distribute after systemic exposure.The scientific development of manufactured nanomaterials for drug delivery is increasing rapidly. One of the most prominent applications is topical drug delivery, where cutaneous, ocular, and nasal exposure becomes even more relevant. These targets are the first barrier that nanoparticles encounter when in contact with the human body.The contributors addresses a representative set of the broad spectrum of nanopharmaceuticals currently being used, including cationic lipid nanoparticles, polymeric PLGA, PLA nanoparticles, biomacromolecules-based nanoparticles, and other scaffolds tissue engineered skin substitutes. Regulation and risk is also covered, since the safety of these nanophamaceuticals still represents a barrier to their wide innovative use. - Provides the reader with a thorough knowledge of the safety aspects of nanopharmaceuticals which are currently under research - Focuses on the characterization and quantification of the nanopharmaceuticals - Allows readers to understand the correlation between the nature of the materials and their potential nanotoxicological effects - Includes an overview of regulatory aspects related to the R&D of nanopharmaceuticals




Contrast Media in Ultrasonography


Book Description

Examines in detail the different clinical applications of microbubble-based contrast agents. Explains the principles underlying the use of contrast-specific imaging techniques and the examination methodology. Contains numerous high-quality illustrations, including many in color. Written by recognized experts.




DeVita, Hellman, and Rosenberg's Cancer


Book Description

Presenting comprehensive, cutting-edge information on the science of oncology and the multimodality treatment of every cancer type, this eighth edition--now in full color--contains more than 40 brand-new chapters, and more than 70 chapters have been rewritten by new contributing authors.




Management of Peritoneal Metastases- Cytoreductive Surgery, HIPEC and Beyond


Book Description

The widespread acceptance among the oncology community at large of cytoreductive surgery and HIPEC as a potentially curative treatment for peritoneal metastases has paved the way for innovative new therapies that could benefit a larger proportion of patients. Much has been and continues to be published on this subject. This book provides comprehensive reviews on the various aspects of managing peritoneal metastases. The authors highlight essential practical issues that surgical oncologists encounter in their day-to-day practice, and try to before provide evidence based answers to address them. All chapters were written and/or reviewed by leading experts in this field.