Critical Reviews in Therapeutic Drug Carrier Systems最新文献

Unmodified nanocarriers used in the chemotherapy of cancers and various infectious diseases exhibit prolonged blood circulation time, prevent enzymatic degradation and increase chemical stability of encapsulated therapeutics. However, off-target effect and lack of specificity associated with unmodified nanoparticles (NPs) limit their applications in the health care system. Mannose (Man) receptors with significant overexpression on antigen-presenting cells and macrophages are among the most admired targets for cancer and anti-infective therapeutics. Therefore, development of Man functionalized nanocarriers targeting Man receptors, for target specific drug delivery in the chemotherapy have been extensively studied. Present review expounds diverse Man-conjugated NPs with their potential for targeted drug delivery, improved biodistribution profiles and localization. Additionally, the review gives detailed account of the interactions of mannosylated NPs with various biological systems and their characterization not discussed in earlier published reports is discussed.

This work is an effort to first introduce plant-based gums and discussing their drug delivery applications. The composition of these plant gums and their major characteristics, which make them suitable as pharmaceutical excipients are also described in detail. The various modifications methods such as physical and chemical modifications of gums and polysaccharides have been discussed along with their applications in different fields. Consequently, plant-based gums modification such as etherification and grafting is attracting much scientific attention to satisfy industrial demand. The evaluation tests to characterize gum-based drug delivery systems have been summarized. The release behavior of drug from plant-gum-based drug delivery is being discussed. Thus, this review is an attempt to critically summarize different aspect of plant-gum-based polysaccharides to be utilized in drug delivery systems having potential industrial applications.

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease with a complex pathophysiology. Treatment of AD remains challenging owing to the presence of a wide spectrum of clinical phenotypes and limited response to existing therapies. However, recent genetic, immunological, and pathophysiological insights into the disease mechanism resulted in the invention of novel therapeutic drug candidates. This review provides a comprehensive overview of current therapies and assesses various novel drug delivery strategies currently under clinical investigation. Further, this review majorly emphasizes on various topical treatments including emollient therapies, barrier repair agents, topical corticosteroids (TCS), phosphodiesterase 4 (PDE4) inhibitors, calcineurin inhibitors, and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway inhibitors. It also discusses biological and systemic therapies, upcoming treatments based on ongoing clinical trials. Additionally, this review scrutinized the use of pharmaceutical inactive ingredients in the approved topical dosage forms for AD treatment.

Treatments for late-stage prostate cancer (CaP) have not been very successful. Frequently, advanced CaP progresses to castration-resistant prostate cancer (CRPC), with 50#37;-70% of patients developing bone metastases. CaP with bone metastasis-associated clinical complications and treatment resistance presents major clinical challenges. Recent advances in the formulation of clinically applicable nanoparticles (NPs) have attracted attention in the fields of medicine and pharmacology with applications to cancer and infectious and neurological diseases. NPs have been rendered biocompatible, pose little to no toxicity to healthy cells and tissues, and are engineered to carry large therapeutic payloads, including chemo- and genetic therapies. Additionally, if required, targeting specificity can be achieved by chemically coupling aptamers, unique peptide ligands, or monoclonal antibodies to the surface of NPs. Encapsulating toxic drugs within NPs and delivering them specifically to their cellular targets overcomes the problem of systemic toxicity. Encapsulating highly labile genetic therapeutics such as RNA within NPs provides a protective environment for the payload during parenteral administration. The loading efficiencies of NPs have been maximized while the controlled their therapeutic cargos has been released. Theranostic ("treat and see") NPs have developed combining therapy with imaging capabilities to provide real-time, image-guided monitoring of the delivery of their therapeutic payloads. All of these NP accomplishments have been applied to the nanotherapy of late-stage CaP, offering a new opportunity for a previously dismal prognosis. This article gives an update on current developments in the use of nanotechnology for treating late-stage, castration-resistant CaP.

Osteoporosis is a bone incapacitating malady which globally accounts for over hundred million fractures annually. Therapeutic interventions for management of osteoporosis are divided as antiresorptive agents and osteoanabolic agents. Teriparatide is the only osteoana-bolic peptide which is available world-wide for the treatment of osteoporosis. It is administered as a daily subcutaneous injection for the treatment of osteoporosis which results in both poor patient compliance and increase in the cost of the therapy. Even after 20 years of clinical use of teriparatide, no formulation of teriparatide has yet been translated from lab to clinic which can be delivered by non-invasive route The present review critically discusses attempts made by the researchers for efficient delivery of teriparatide through various non-invasive routes such as oral, nasal, pulmonary, and transdermal route. It also discusses long-acting injectable formulations of teriparatide to improve patient compliance. Understanding on the pharmacology of teriparatide highlights the enhanced effectiveness of intermittent/pulsatile mode of teriparatide delivery which has also been elaborated. In addition, targeted delivery of teriparatide using different bone specific targeting moieties has been also discussed.

Macrophages are immuno cells with high flexibility among hematopoietic system. Macrophages are tangled with many diseases like chronic inflammatory, atherosclerosis, autoimmune, and cancer. Macrophages play a major role in developing the inflammation and meanwhile resolving the damage occurred during these disease conditions. Therefore, the use of macrophages in targeted drug delivery appeared to be a promising approach in modifying the microenvironment of inflammatory diseases. The macrophages with cellular backpacks loaded with drugs were appeared to be the effective drug transporter to the brain inflammation. Till date, among the different carrier systems emerged among macrophage targeting: liposomes, microspheres, nanoparticles, and dendrimers were extensively studied. The physicochemical properties like components, lipophilicity, hydrophilicity, ligand presence, and concentration of these carriers may vary the efficacy and specificity of drug targeting to macrophages. The present review provides an insight into M1 and M2 macrophages characteristics, mainly discussed the role of macrophages in regulating several inflammatory diseases. This article underlines the current status and application of different carriers for targeted drug delivery to macrophages along with their efficacy and specificity. In general, the targeted drug delivery was achieved using the carrier systems by removing the intrinsic pathway and bio protection which is offered to the therapeutic molecules. Further, the review also summarizes the newer approaches for macrophage targeting with a brief overview on recent advances and future prospects.

Quality by design (QbD) has recently fascinated researchers for utilizing it in various arenas of pharma trends. By overcoming the conventional process, QbD prevents the risk of errors caused by the 'guess and by god approach'. This framework fosters profound knowledge of product and process quality by implying sound science and risk assessment strategies. The virtue of QbD leads to the collaborative contribution to pharmaceutical industrialists and satisfies the regulatory bodies. Additionally, leading to rapid production, saves time and expenditure, tremendous versatility, provides immense knowledge, improves robustness, higher consistency, reduces user's dilemma, decreases certainty of failure, declining inter-batch variation in pharmaceutical development. In this ever-increasing continuous production world, regulatory organizations such as the U.S. Food & Drug Administration and the International Conference on Harmonization recommend Q8 to Q14 guidelines in order to obtain the desired quality product. This review extensively discusses on various approaches of QbD for the pharmaceutical development of nano-carrier drug delivery systems. Additionally, QbD's applications in process and analytical method development techniques are documented.

Anti-cancer drugs are mostly limited in their use due to poor physicochemical and biopharmaceutical properties. Their lower solubility is the most common hurdle limiting their use upto their potential. In the recent years, the cyclodextrin (CD) complexation have emerged as existing approach to overcome the problem of poor solubility. CD-based nano-technological approaches are safe, stable and showed well in vivo tolerance and greater payload for encapsulation of hydrophobic drugs for the targeted delivery. They are generally chosen due to their ability to get self-assembled to form liposomes, nanoparticles, micelles and nano-sponges etc. This review paper describes a birds-eye view of the various CD-based nano-technological approaches applied for the delivery of anti-cancer moieties to the desired target such as CD based liposomes, niosomes, niosoponges, micelles, nanoparticles, monoclonal antibody, magnetic nanoparticles, small interfering RNA, nanorods, miscellaneous formulation of anti-cancer drugs containing CD. Moreover, the author also summarizes the various shortcomings of such a system and their way ahead.

Most of the oral drug delivery systems demand better retention of drug in the gastrointestinal tract (GIT) for better bioavailability. One of the tools for better gastric retention of the drug is to administer it as a floating drug delivery system (FDDS) by reducing its density, compared to the gastric fluids. This system is helpful to overcome the problems associated with the conventional pharmaceutical dosage forms. The present work is an effort to systematically review the latest advancements in FDDS with a major spotlight on how these systems act to make the dosage form float in the gastric fluid for the slow release, better gastric retention, and improved bioavailability of the orally administered drug. As managing diseases through medicines is going in a new age in which innovative delivery system is being used as well as made accessible for remedial use. The excipients used for making such oral gastro-retention dosage forms (GRDF) to provide sustained release profile of drugs along with the work done so far by different scientists in the past two decades; the patents filed in this area; the evaluation methods for checking the quality of FDDS; and their applications are the major highlights of this work.