Punctal plugs (PPs) are miniature medical implants that were initially developed for the treatment of dry eyes. Since their introduction in 1975, many PPs made from different materials and designs have been developed. PPs, albeit generally successful, suffer from drawbacks such as epiphora and suppurative canaliculitis. To overcome these issues intelligent designs of PPs were proposed (e.g. SmartPLUG™ and Form Fit™). PPs are also gaining interest among pharmaceutical scientists for sustaining drug delivery to the eye. This review aims to provide an overview of PPs for dry eye treatment and drug delivery to treat a range of ocular diseases. It also discusses current challenges in using PPs for ocular diseases.
Regenerative medicine has rapidly evolved over the past decade owing to its potential applications to improve human health. Targeted differentiations of stem cells promise to regenerate a variety of tissues and/or organs despite significant challenges. Recent studies have demonstrated the vital role of the physical microenvironment in regulating stem cell fate and improving differentiation efficiency. In this review, we summarize the main physical cues that are crucial for controlling stem cell differentiation. Recent advances in the technologies for the construction of physical microenvironment and their implications in controlling stem cell fate are also highlighted.
Resistance of cancer cells to anticancer drugs is the main reason for the failure of traditional cancer treatments. Various cellular components and different loops within the signaling pathways contribute to drug resistance which could be modulated with the aim to restore drug efficacy. Unveiling the molecular mechanisms for cancer drug resistance has now paved the way for the development of novel approaches to regulate the response rates to anticancer drugs at the genetic level. The recent progress on identification and validation of the vital genes directly or indirectly involved in development of cancer drug resistance with the aid of the specific knock down ability of RNA interference technology is discussed in this review.
Immune checkpoint inhibitors (ICIs) are revolutionizing the treatment of many cancers and have demonstrated their potential as 'cancer terminators'. However, ICI treatment also has constraints, such as its immune-related adverse events (irAEs) and therapeutic resistance. These drawbacks are gradually being overcome through better knowledge of the immune system, history of disease, duration of treatment, combinational drug regimes, adequate biomarkers, and effective patient response monitoring. In this review, we discuss the present ICI therapy landscape and its therapeutic outcomes for various diseases. We also highlight biomarkers related to the ICI response.
Gold nanoparticles (AuNPs) have garnered much attention as contrast agents for computerized tomography (CT) because of their facile synthesis and surface functionalization, in addition to their significant X-ray attenuation and minimal cytotoxicity. Cell labeling using AuNPs and tracking of the labeled cells using CT has become a time-efficient and cost-effective method. Actively targeted AuNPs can enhance CT contrast and sensitivity, and further reduce the radiation dosage needed during CT imaging. In this review, we summarize the state-of-the-art use of AuNPs in CT for cell tracking, including the precautionary steps necessary for their use and the difficulty in translating the process into clinical use.
Peptides and proteins have emerged as potential therapeutic agents and, in the search for the best treatment regimen, the oral route has been extensively evaluated because of its non-invasive and safe nature. The physicochemical properties of peptides and proteins along with the hurdles in the gastrointestinal tract (GIT), such as degrading enzymes and permeation barriers, are challenges to their delivery. To address these challenges, several conventional and novel approaches, such as nanocarriers, site-specific and stimuli specific delivery, are being used. In this review, we discuss the challenges to the oral delivery of peptides and the approaches used to tackle these challenges.
Smart nanocarriers obtained from bacteria and viruses offer excellent biomimetic properties which has led to significant research into the creation of advanced biomimetic materials. Their versatile biomimicry has application as biosensors, biomedical scaffolds, immobilization, diagnostics, and targeted or personalized treatments. The inherent natural traits of biomimetic and bioinspired bacteria- and virus-derived nanovesicles show potential for their use in clinical vaccines and novel therapeutic drug delivery systems. The past few decades have seen significant progress in the bioengineering of bacteria and viruses to manipulate and enhance their therapeutic benefits. From a pharmaceutical perspective, biomimetics enable the safe integration of naturally occurring bacteria and virus particles to achieve high, stable rates of cellular transfection/infection and prolonged circulation times. In addition, biomimetic technologies can overcome safety concerns associated with live-attenuated and inactivated whole bacteria or viruses. In this review, we provide an update on the utilization of bacterial and viral particles as drug delivery systems, theranostic carriers, and vaccine/immunomodulation modalities.
Theranostics has the potential to revolutionize the diagnosis, treatment, and prognosis of cancer, where novel drug delivery systems could be used to detect the disease at an early stage with instantaneous treatment. Various preclinical approaches of nanoemulsions with entrapped contrast and chemotherapeutic agents have been documented to act specifically on the tumor microenvironment (TME) for both diagnostic and therapeutic purposes. However, bringing these theranostic nanoemulsions through preclinical trials to patients requires several fundamental hurdles to be overcome, including the in vivo behavior of the delivery tool, degradation, and clearance from the system, as well as long-term toxicities. Here, we discuss recent advances in the application of nanoemulsions in molecular imaging with simultaneous therapeutic efficacy in a single delivery system.
A tumor serves as a major avenue in drug development owing to its complexity. Conventional therapies against tumors possess limitations such as suboptimal therapeutic efficacy and extreme side effects. These display poor pharmacokinetics and lack specific targeting, with non-specific distribution resulting in systemic toxicity. Therefore, nanocarriers targeted against cancers are increasingly being explored. Nanomedicine aids in maintaining a balance between efficacy and toxicity by specifically accumulating in tumors. Nanotherapeutics possess advantages such as increased solubility of chemotherapeutics, encapsulation of multiple drugs and improved biodistribution, and can ensure tumor-directed drug delivery and release via the approaches of passive targeting and active targeting. This review aims to offer a general overview of the current advances in tumor-targeting nanocarriers for clinical and diagnostic use.
The merger of nanotechnology and combination chemotherapy has shown notable promise in the therapy of resistant tumors. The latest scientific attention encompasses the engagement of anticancer drugs in combination with small interfering (si)RNAs, such as VEGF, XLAP, PGP, MRP-1, BCL-2 and cMyc, to name but a few. siRNAs have shown immense promise to knockout drug resistance genes as well as to recover the sensitivity of resistant tumors to anticancer therapy. The nanotechnology approach could also protect siRNA against RNAse degradation as well as prevent off-target effects. In this article, we discuss the approaches that have been used to deliver of siRNA in combination with chemotherapeutic drugs to treat resistant tumors. We also discuss the stipulations that must be considered in formulating a nanotechnology-assisted siRNA-drug cancer therapy.
Dendrimers are novel nanoarchitectures with unique properties including a globular 3D shape, a monodispersed unimicellar nature and a nanometric size range. The availability of multiple peripheral functional groups and tunable surface engineering enable the facile modification of the dendrimer surface with different therapeutic drugs, diagnostic agents and targeting ligands. Drug encapsulation, and solubilizing and passive targeting also equally contribute to the therapeutic use of dendrimers. In this review, we highlight recent advances in the delivery of anticancer drugs using dendrimers, as well as other biomedical and diagnostic applications. Taken together, the immense potential and utility of dendrimers are envisaged to have a significant positive impact on the growing arena of drug delivery and targeting.
Topical photodynamic therapy (PDT) is a non-invasive technique used in the treatment of malignant and non-malignant skin diseases. It offers great promise because of its simplicity, enhanced patient compliance, localisation of the photosensitizer, as well as the use of light and oxygen to achieve photocytotoxicity. Despite progress in photosensitizer-mediated topical PDT, its clinical application is limited by poor penetration of photosensitizers through the skin. Therefore, much effort has been made to develop nanocarriers that can tackle the challenges of conventional photosensitizer-mediated PDT for topical delivery. This review discusses recent data on the use of different types of lipid-based nanocarriers in delivering photosensitizer for topical PDT.
Global research on polyelectrolytes at a fundamental and applied level is intensifying because the advantages of sustainability are being accepted in academia and industrial research settings. During recent decades, polyelectrolytes became one of the most attractive subjects of scientific research owing to their great potential in the areas of advanced technologies. Polyelectrolytes are a type of polymer that have multitudinous ionizable functional groups. Ionized polyelectrolytes in solution can form a complex with oppositely charged polyelectrolytes - a polyelectrolyte complex (PEC). The present article provides a comprehensive review on PECs and their classification, theory and characterization, as well as a critical analysis of the current research.
To avoid tissue rejection during organ transplantation, research has focused on the use of tissue engineering to regenerate required tissues or organs for patients. The biomedical applications of hyperbranched, multivalent, structurally uniform, biocompatible dendrimers in tissue engineering include the mimicking of natural extracellular matrices (ECMs) in the 3D microenvironment. Dendrimers are unimolecular architects that can incorporate a variety of biological and/or chemical substances in a 3D architecture to actively support the scaffold microenvironment during cell growth. Here, we review the use of dendritic delivery systems in tissue engineering. We discuss the available literature, highlighting the 3D architecture and preparation of these nanoscaffolds, and also review challenges to, and advances in, the use dendrimers in tissue engineering. Advances in the manufacturing of dendritic nanoparticles and scaffold architectures have resulted in the successful incorporation of dendritic scaffolds in tissue engineering.
Maintenance of oral health is a major challenge in dentistry. Different materials have been used to treat various dental diseases, although treatment success is limited by features of the biomaterials used. To overcome these limitations, materials incorporated with nanoparticles (NPs) can be used in dental applications including endodontics, periodontics, tissue engineering, oral surgery, and imaging. The unique properties of NPs, including their surface:volume ratio, antibacterial action, physical, mechanical, and biological characteristics, and unique particle size have rendered them effective vehicles for dental applications. In this review, we provide insights into the various applications of NPs in dentistry, including their benefits, limitations, properties, actions and future potential.
Artificial intelligence (AI) uses personified knowledge and learns from the solutions it produces to address not only specific but also complex problems. Remarkable improvements in computational power coupled with advancements in AI technology could be utilised to revolutionise the drug development process. At present, the pharmaceutical industry is facing challenges in sustaining their drug development programmes because of increased R&D costs and reduced efficiency. In this review, we discuss the major causes of attrition rates in new drug approvals, the possible ways that AI can improve the efficiency of the drug development process and collaboration of pharmaceutical industry giants with AI-powered drug discovery firms.
Lyotropic nonlamellar liquid crystalline nanoparticles (NPs) (LCN), such as cubosomes and hexosomes, are useful tools for applications in drug delivery because of their unique structural properties. LCNs are highly versatile carriers that can be applied for use with topical, oral, and intravenous treatments. In recent years, significant research has focused on improving their preparation and characterization, including controlling drug release and enhancing the efficacy of loaded bioactive molecules. Nevertheless, the clinical translation of LCN-based carriers has been slow. In this review, we highlight recent advances and challenges in the development and application of LCN, providing examples of their topical, oral, and intravenous drug delivery applications, and discussing translational obstacles to LCN as a NP technology.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by degeneration of dopaminergic neurons. Motor features such as tremor, rigidity, bradykinesia and postural instability are common traits of PD. Current treatment options provide symptomatic relief to the condition but are unable to reverse disease progression. The conventional single-target therapeutic approach might not always induce the desired effect owing to the multifactorial nature of PD. Hence, multitarget strategies have been proposed to simultaneously target multiple proteins involved in the development of PD. Herein, we provide an overview of the pathogenesis of PD and the current pharmacotherapies. Furthermore, rationales and examples of multitarget approaches that have been tested in preclinical trials for the treatment of PD are also discussed.
Andrographolide (AGP), a naturally occurring bioactive compound, has been investigated as a lead compound in cancer drug development. Its multidimensional therapeutic effects have raised interest among medicinal chemists, which has led to extensive structural modification of the compound, resulting in analogues with improved pharmacological and pharmaceutical properties. Nevertheless, the analogues with the improved properties need to be rigorously studied to identify drug-like lead compounds. We scrutinised articles published from 2012 to 2018, to objectively provide opinions on the mechanisms of action of AGP and its analogues, as well as their potential as viable anticancer drugs. Preclinical and clinical data, along with the extensive medicinal chemistry efforts, indicate the compounds are potential anticancer agents with specific value in treating recalcitrant cancers such as pancreatic and lung cancers.