Critical Reviews in Therapeutic Drug Carrier Systems最新文献

The pediatric population is generally considered as "miniature adults," but they actually differ from adults due to their different body compositions and varied stages of organ development, which alter essential biopharmaceutical parameters. The physiological differences between the pediatric population and the adult population alter the essential kinetics and dynamics of the same drug administered at the same dose. For pediatric patients, the drug dose is generally calculated using different formulas based on age, body surface area, or weight, or is simply reduced to half of adult dose. This, however, is not the correct practice. New approaches have emerged for designing customized formulations and medical devices for the pediatric population. Examples of customized formulations are "mini-tablets" and "oro-dispersible films," which attempt to ease the administration of solid oral dosage forms. These specially designed medical devices have shown the ability to overcome many challenges in dose administration to children. One such medical device is the "oral solid dosage pen," which allows for dose adjustment by cutting a tablet-like drug carrier at a predefined height and offers flexibility and convenience for dose administration to the pediatric population. Other medical devices, such as the Nipple Shield Delivery System (NSDS) and Medibottle also aid in efficient drug delivery to pediatrics. This review summarizes the challenges in dosage form design and advances in suitable medical devices for better administration to the pediatric population to overcome accidents due to medical errors, incomplete absorption, and toxicity.

Chemotherapy of cancer is still considered a complex phenomenon given that single chemotherapeutic agents cannot be administered for a long period of time because of the development of drug resistance and severe side effects. Nanodrug delivery systems (NDDSs) such as nanoparticles and liposomes are being investigated to enhance the safety and efficacy of anticancer agents. NDDS-based delivery of a single agent is not found to be effective in long-term anticancer therapy. Codelivery of more than one anticancer agent using liposomes shows great potential since it exhibits simultaneous synergistic therapeutic manifestations at the tumor site and enhances therapeutic efficacy in terms of the low-dose requirement of each agent and diminished side effects. Liposomes are lipid vesicles arranged in concentric bilayers with an aqueous core; they are versatile nanocarriers that accommodate the diverse nature of anticancer drugs (both hydrophobic and hydrophilic) at the same time. They offer a number of advantages for combinatorial drug delivery in terms of increased blood circulation, selective accumulation at tumor tissues, and stimuli responsiveness. Various combination of drugs such as paclitaxel (PTX) and topotecan, sunitinib and irinotecan, and combretastin A-4 and doxorubicin have been reported for cancer chemotherapy using liposomes. This review focuses on recent scenarios of combinatorial drug delivery using liposomes for better chemotherapeutic outcomes. This assemblage can be of great importance to researchers looking for advances in novel drug delivery approaches for better cancer treatment.

Colorectal cancer is the third most common cancer in the world, affecting both men and women, and it is one of the leading causes of cancer related deaths worldwide. Current treatment modalities employed for colorectal cancer management have their own share of drawbacks, such as toxicity due to nonspecific action and chemoresistance that may develop during treatment. The quest and pursuit for newer drugs which can overcome these drawbacks has led to extensive research on plant derived phytoconstituents. Herbal molecules are known to have promising therapeutic efficacy and less toxicity as compared to the current chemotherapeutic drugs of allopathic regimen. However most of these herbal molecules have low bioavailability as a result their therapeutic efficacy gets compromised. Integration of modern delivery approaches with these herbal molecules and presenting them in the form of nanocarriers will help alleviate these drawbacks. This review describes herbal drugs that have potential for treatment of colorectal cancer and nanotechnology strategies widely investigated for the delivery of these herbal molecules. Targeted delivery methods include use of such components as polymeric nanoparticles, liposomes, dendrimers, magnetic nanoparticles, solid lipid nanoparticles, and nanoemulsions. The paper also discusses in detail the formulation aspects of herbal nanocarriers, their design development, and preclinical assessment.

Despite extraordinary advances that have been made in cancer therapy, the number of cancer cases continue to surge, making it the leading cause of death across the world. As a result, early detection is one of the key aspects in the battle against the disease. Screening and early diagnosis play a pivotal role for effective treatment and to lower the cancer mortality rate. Cancer nanotechnology is a new branch in biology that provides a link between nanotechnology and clinical cancer research. Moreover, it also aims to integrate the advancements made in the manufacture of nanoscale devices with cellular and molecular components associated with cancer diagnosis and therapy. Understanding these new technologies is crucial to integrating these practices into clinical settings. This novel approach has facilitated the conjugation of nanoscale devices with agents such as tumor-specific li-gands, antibodies, and imaging probes. This review summarizes the advancements made in nanotechnology based approaches in diagnosing cancer. Coupling of nanoparticles with targeting molecules enables an efficient interaction between biological systems with extraordinary accuracy. The progress associated with nanoscale devices such as metal based nanomaterials, exosomes, magnetic nanoparticles, in addition to quantum dots and lab on chip devices with regard to diagnostic applications has been discussed. We summarize how nanoparticles take advantage of the tumor microenvironment for targeting cancer cells. Further, the review outlines the drawbacks, challenges, and future prospects associated with these techniques as effective strategies to replace current clinical trends.

Multidrug resistance (MDR) remains a major obstacle to ensure effective chemotherapy in cancer patients. Several factors could be associated with cancer cells' drug resistance such as overexpression of P-glycoprotein (P-gp), cancer stem cells (CSCs), defect in apoptosis, mutation and alteration in DNA repair pathways, angiogenesis, autophagy, and modulation in metabolic enzymes. Until now, drug efflux by ABC transporters has been a univocal and well-established mechanism of chemotherapeutic associated drug resistance. To explore the mechanics involved in ABC transporter associated drug resistance, many crucial studies have been conducted from identification of drug binding sites to elucidation of their structure. Due to our continuous battle with drug resistance, several strategies have been employed to combat MDR, including P-gp modulators, siRNAs, antibodies, as well as peptides. Furthermore, various nanoparticle and different effective combination nanomedicine strategies also suggest some exciting results. Thus, to improve nanomedicine approaches to overcome MDR, in this evolutionary review, we have focused on fundamentals of possible strategies as well as the latest accomplishments to reverse MDR.

Many of the recently approved drug molecules that are therapeutically successful are found to be incompatible for the development of a novel delivery system and to take part in various health care management. Regardless of having better therapeutic properties, these molecules are barred from their effective clinical uses. The main reason attributed to it is poor solubility and/or poor permeability of drugs which finally emerges the drug to be low bioavailable. Nanoemulsions are one of the most acceptable nanolipoidal drug delivery system and appears to be a hope for the delivery of many of the Biopharmaceutical Classification System (BCS) class II and IV drugs. A nanoemulsion is a thermodynamically unstable isotropic mixture of oil, surfactant, and co-surfactants and is biphasic in nature. It can be either water in oil or oil in water and droplets are found in the range of 5 to 500 nm. The manufacturing and fabrication of nanoemulsions involve various natural, synthetic and semi synthetic materials using either low or high-energy methods. Application of nanoemulsions as a novel drug delivery system through several routes, especially oral, transdermal, ophthalmic, and intranasal, have been increased for various pharmacological aspects such as cardiovascular, anticancer, antimicrobial, and ophthalmic due to their stability, high solubilization capacity, and ease of preparation. The objective of this review is to focus on the aspects of manufacturing, fabrication, application, and some toxicological concerns related to nanoemulsions.

Non-selectivity and dose-dependent side effects of doxorubicin (DOX), particularly cardio-toxicology as well as multidrug resistance in various tumor cells, have increased the demand for novel formulations with suitable efficiency and safety. Microformulations and nanoformulations have been shown to have satisfactory responses compared with that of conventional formulations. In this review, recent advances alongside the advantages and disadvantages of microformulations and nanoformulations are discussed. Doxil and Caelyx (PEGylated forms) as well as Myocet (non-PEGylated form) are presented as approved liposomal forms by the U.S. Food and Drug Administration to increase blood circulation half-life of DOX. Liposomes, micelles, hydrogels, lipid nanoparticles (NPs), polymeric NPs, polymersomes, metal/metal oxide NPs, mesoporous silica NPs, carbon-based NPs, and quantum dots are all major carriers for DOX and discussed accordingly. Considering all extracellular and intracellular conditions of cancer cells is an indispensable affair to obtain promising DOX carriers. Lack of a comprehensive related to drug-resistance cancer cells particularly in metastasis stages is an important hindrance to get acceptable results. Understanding of the drug resistance mechanisms in cancers cells particularly, in metastasis stages, is a critical factor to prepare efficient formulations.

In this review, we describe the advances in oral drug delivery approaches for taxanes for successful therapeutic outcome. Taxanes (paclitaxel and docetaxel) have unwanted pharmacokinetic profiles when they are given in their current dosage forms. Taxanes have low bioavailability, are extensively metabolized by CYP3A, and have a high affinity for P-glycoprotein. Regardless of dosage schedule, the overall docetaxel or paclitaxel dose that a patient can tolerate at a given interval remains similar. Currently, there are no commercially available oral taxane nanoformulations, and there are still several challenges to overcome. Nano-based formulations may offer the best solutions to problems involving the safety and effectiveness of taxane delivery. Thus, further research is necessary before such taxane nanoformulations can be manufactured for clinical use.

Nanotechnology is opening up new opportunities in drug delivery, including oral delivery, and it may reduce toxicity and increase drug ability. Presently, researchers are expanding their knowledge in the development of oral nanomedicine to extend the scope of oral drug delivery and exhibit excellent platforms for drug transportation, target, and controlled release. The present review is an attempt to define updated oral nanostructured systems for the delivery of a wide range of drugs. The review also focuses on the use of different polymeric and other materials, technologies adopted, and benefits/drawbacks of delivery systems.

Nanostructured drug delivery formulations have lately gained enormous attention, contributing to their systematic development. Issuance of quality by design (QbD) guidelines by ICH, FDA, and other federal agencies, in this regard, has notably influenced the overall development of drug products, enabling holistic product and process understanding. Owing to the applicability of QbD paradigms, a science lately christened as formulation by design (FbD) has been dedicated exclusively to QbD-enabled drug product development. Consisting of the principal elements of design of experiments (DoE), quality risk management (QRM), and QbD-enabled product comprehension as the fundamental tools in the implementation of FbD, a variety of drug nanocargos have been successfully developed with FbD paradigms and reported in the literature. FbD aims to produce novel and advanced systems utilizing nominal resources of development time, work effort, and money. A systematic FbD approach envisions the entire developmental path through pivotal milestones of risk assessment, factor screening and optimization (both using appropriate experimental designs), multivariate statistical and optimum search tools, along with response surface modeling, usually employing suitable computer software. The design space is one of the fundamental elements of FbD providing the most sought-after regulatory flexibility to pharma companies, postapproval. The present paper provides a bird's eye view of the fundamental aspects of FbD terminology, methodology, and applications in the development of a wide range of nanocargos, as well as a discussion of trends from both technological and regulatory perspectives.