Critical Reviews in Therapeutic Drug Carrier Systems最新文献

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.

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.

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.

Nanotechnology has made great contributions in the development of materials with potential application in different areas, especially in the pharmaceutical sector, where nano-systems are being intensely studied for controlled drug release. These innovative systems are composed of structures such as nanoparticles, nanoemulsions, and cyclodextrins, with the aim of promoting enhanced bioavailability of bioactive molecules. Among these nanocarriers, vesicles such as liposomes and polymersomes are considered to be promising alternatives in delivering hydrophilic and lipophilic drugs. They have different classifications according to their composition, among which are hybrid vesicles, which unlike liposomes are composed of both lipids and polymers. These vesicular systems stand out for combining the advantages of both components, overcoming the limitations of traditional systems imposed by low stability and premature release of the encapsulated active substance. The polymers applied in hybrid vesicles can make up the membrane structure itself or be employed to coat preformed vesicles. Due to the relevance of these systems, this work covers their characteristics and summarizes recent articles about them in the literature.

Nail psoriasis is a chronic condition which causes pain and functional impairment; thus, it restricts the activities of daily living and worsens the quality of life. Different chemotherapeutic options are available for treating nail psoriasis such as systemic, intralesional, and topical therapies. However, current chemotherapy suffers from several limitations and to overcome them, new advancements are being made worldwide. Various reports have been published on current progress in the treatment of nail psoriasis such as clinical efficacy studies of novel antipsoriatic agents and novel formulation strategies for current chemotherapy. There are several novel nail formulations for the treatment of nail disorders, particularly onychomycosis, such as vesicular colloidal structure (liposomes, niosomes, transfersomes, ethosomes, etc.) and nonvesicular colloidal structures (nano-emulgel, nanocapsules, thermosensitive gel, etc.) These formulations can also prove beneficial for the treatment of nail psoriasis, and will be heavily explored in the near future. This review provides a brief introduction to the disease, its pathogenesis, and its treatment modalities. The review also throws light onto progress and future perspectives in nail psoriasis treatment.

Globally, lung cancer is one of the most frequently diagnosed and deadliest types of cancer. Lung cancer imaging can be performed using both invasive and noninvasive techniques, including magnetic resonance, positron emission tomography, single photon emission computed tomography, chest radiography, and computed tomography. But nonspecific contrast agents and radiopharmaceuticals are insufficient for early and specific diagnoses and imaging. In the case of lung cancer therapy, conventional therapeutic agents and radiotherapy may cause severe and systemic adverse and toxic effects and fail to eradicate all tumor tissue. Therefore, formulation of novel, targeted, and specific agents is critically important to overcome these challenges. In this review, we summarize lung cancer classification, current methods for lung cancer imaging and therapy, and future options containing nanosized systems for lung cancer imaging and/or therapy.