Oral delivery of peptide and protein drugs faces immense challenge partially due to the gastrointestinal (GI) environment. In spite of considerable efforts by industrial and academic laboratories, no ...major breakthrough in the effective oral delivery of polypeptides and proteins has been accomplished. Upon oral administration, gastrointestinal epithelium acts as a physical and biochemical barrier for absorption of proteins resulting in low bioavailability (typically less than 1–2%). An ideal oral drug delivery system should be capable of (a) maintaining the integrity of protein molecules until it reaches the site of absorption, (b) releasing the drug at the target absorption site, where the delivery system appends to that site by virtue of specific interaction, and (c) retaining inside the gastrointestinal tract irrespective of its transitory constraints. Various technologies have been explored to overcome the problems associated with the oral delivery of macromolecules such as insulin, gonadotropin-releasing hormones, calcitonin, human growth factor, vaccines, enkephalins, and interferons, all of which met with limited success. This review article intends to summarize the physiological barriers to oral delivery of peptides and proteins and novel pharmaceutical approaches to circumvent these barriers and enhance oral bioavailability of these macromolecules.
Anatomy and physiology of the eye makes it a highly protected organ. Designing an effective therapy for ocular diseases, especially for the posterior segment, has been considered as a formidable ...task. Limitations of topical and intravitreal route of administration have challenged scientists to find alternative mode of administration like periocular routes. Transporter targeted drug delivery has generated a great deal of interest in the field because of its potential to overcome many barriers associated with current therapy. Application of nanotechnology has been very promising in the treatment of a gamut of diseases. In this review, we have briefly discussed several ocular drug delivery systems such as microemulsions, nanosuspensions, nanoparticles, liposomes, niosomes, dendrimers, implants, and hydrogels. Potential for ocular gene therapy has also been described in this article. In near future, a great deal of attention will be paid to develop non-invasive sustained drug release for both anterior and posterior segment eye disorders. A better understanding of nature of ocular diseases, barriers and factors affecting in vivo performance, would greatly drive the development of new delivery systems. Current momentum in the invention of new drug delivery systems hold a promise towards much improved therapies for the treatment of vision threatening disorders.
Ocular drug delivery is challenging due to the presence of anatomical and physiological barriers. These barriers can affect drug entry into the eye following multiple routes of administration (e.g., ...topical, systemic, and injectable). Topical administration in the form of eye drops is preferred for treating anterior segment diseases, as it is convenient and provides local delivery of drugs. Major concerns with topical delivery include poor drug absorption and low bioavailability. To improve the bioavailability of topically administered drugs, novel drug delivery systems are being investigated. Nanocarrier delivery systems demonstrate enhanced drug permeation and prolonged drug release. This review provides an overview of ocular barriers to anterior segment delivery, along with ways to overcome these barriers using nanocarrier systems. The disposition of nanocarriers following topical administration, their safety, toxicity and clinical trials involving nanocarrier systems are also discussed.
The electrospinning process has gained popularity due to its ease of use, simplicity and diverse applications. The properties of electrospun fibers can be controlled by modifying either process ...variables (e.g., applied voltage, solution flow rate, and distance between charged capillary and collector) or polymeric solution properties (e.g., concentration, molecular weight, viscosity, surface tension, solvent volatility, conductivity, and surface charge density). However, many variables affecting electrospinning are interdependent. An optimized electrospinning process is one in which these parameters remain constant and continuously produce nanofibers consistent in physicochemical properties. In addition, nozzle configurations, such as single nozzle, coaxial, multi-jet electrospinning, have an impact on the fiber characteristics. The polymeric solution could be aqueous, a polymeric melt or an emulsion, which in turn leads to different types of nanofiber formation. Nanofiber properties can also be modified by polarity inversion and by varying the collector design. The active moiety is incorporated into polymeric fibers by blending, surface modification or emulsion formation. The nanofibers can be further modified to deliver multiple drugs, and multilayer polymer coating allows sustained release of the incorporated active moiety. Electrospun nanofibers prepared from polymers are used to deliver antibiotic and anticancer agents, DNA, RNA, proteins and growth factors. This review provides a compilation of studies involving the use of electrospun fibers in biomedical applications with emphasis on nanoparticle-impregnated nanofibers.
The transdermal route of drugs has received increased attention in recent years due to numerous advantages over the oral and injectable routes, such as avoidance of the hepatic metabolism, protection ...of drugs from the gastrointestinal tract, sustained drug delivery, and good patient compliance. The assessment of ex vivo permeation during the pharmaceutical development process helps in understanding the product quality and performance of a transdermal delivery system. Generally, excised human skin relevant to the application site or animal skin is recommended for ex vivo permeation studies. However, the limited availability of the human skin and ethical issues surrounding the use of animal skin rendered these models less attractive in the permeation study. In the last three decades, enormous efforts have been put into developing artificial membranes and 3D cultured human skin models as surrogates to the human skin. This manuscript provides an insight on the European Medicines Agency (EMA) guidelines for permeation studies and the parameters affected when using Franz diffusion cells in the permeation study. The need and possibilities for skin alternatives, such as artificially cultured human skin models, parallel artificial membrane permeability assays (PAMPA), and artificial membranes for penetration and permeation studies, are comprehensively discussed.
Background
Resveratrol (3, 5, 4′‐trihydroxystilbene), a natural polyphenol and phytoalexin, has drawn considerable attention in the past decade due to its wide variety of therapeutic activities such ...as anticancer, anti‐inflammatory, and antioxidant properties. However, its poor water solubility, low chemical stability, and short biological half‐life limit its clinical utility.
Recent findings
Nanoparticles overcome the limitations associated with conventional chemotherapeutic drugs, such as limited availability of drugs to the tumor tissues, high systemic exposures, and consequent toxicity to healthy tissues. This review focuses on the physicochemical properties of resveratrol, the therapeutic potential of resveratrol nano‐formulations, and the anticancer activity of resveratrol encapsulated nanoparticles on various malignancies such as skin, breast, prostate, colon, liver, ovarian, and lung cancers (focusing on both in vitro and in vivo studies).
Conclusions
Nanotechnology approaches have been extensively utilized to achieve higher solubility, improved oral bioavailability, enhanced stability, and controlled release of resveratrol. The resveratrol nanoparticles have markedly enhanced its anticancer activity both in vitro and in vivo, thus considering it as a potential strategy to fight various cancers.
Multiwalled carbon nanotubes (MWCNTs) are elongated, hollow cylindrical nanotubes made of sp2 carbon. MWCNTs have attracted significant attention in the area of drug delivery due to their high ...drug-loading capacity and large surface area. Furthermore, they can be linked to bioactive ligands molecules via covalent and noncovalent bonds that allow for the targeted delivery of anticancer drugs such as doxorubicin. The majority of methodologies reported for the functionalization of MWCNTs for drug delivery are quite complex and use expensive linkers and ligands. In the present study, we report a simple, cost-effective approach for functionalizing MWCNTs with the carbohydrate ligands, galactose (GA), mannose (MA) and lactose (LA), using lysine as a linker. The doxorubicin (Dox)-loaded functionalized MWCNTs were characterized using FT-IR, NMR, Raman, XRD and FE-SEM. The drug–loaded MWCNTs were evaluated for drug loading, drug release and cell toxicity in vitro, in breast cancer cells. The results indicated that the carbohydrate-modified lysinated MWCNTs had greater Dox loading capacity, compared to carboxylated MWCNTs (COOHMWCNTs) and lysinated MWCNTs (LyMWCNTs). In vitro drug release experiments indicated that the carbohydrate functionalized LyMWCNTs had higher Dox release at pH 5.0, compared to the physiological pH of 7.4, over 120 h, indicating that they are suitable candidates for targeting the tumor microenvironment as a result of their sustained release profile of Dox. Doxorubicin-loaded galactosylated MWCNTs (Dox-GAMWCNTs) and doxorubicin loaded mannosylated MWCNTs (Dox-MAMWCNTs) had greater anticancer efficacy and cellular uptake, compared to doxorubicin–loaded lactosylated MWCNTs (Dox-LAMWCNTs) and pure Dox, in MDA-MB231 and MCF7 breast cancer cells. However, neither the ligand conjugated multiwall blank carbon nanotubes (GAMWCNTs, MAMWCNTs and LAMWCNTs) nor the lysinated multiwalled blank carbon nanotubes produced significant toxicity in the normal cells. Our results suggest that sugar-tethered multiwalled carbon nanotubes, especially the galactosylated (Dox-GAMWCNTs) and mannosylated (Dox-MAMWCNTs) formulations, may be used to improve the targeted delivery of anticancer drugs to breast cancer cells.
Lung cancer is amongst the most pervasive malignancies having high mortality rates. It is broadly grouped into non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). The concept of ...personalized medicine has overshadowed the conventional chemotherapy given to all patients with lung cancer. The targeted therapy is given to a particular population having specific mutations to help in the better management of lung cancer. The targeting pathways for NSCLC include the epidermal growth factor receptor, vascular endothelial growth factor receptor, MET (Mesenchymal epithelial transition factor) oncogene, Kirsten rat sarcoma viral oncogene (KRAS), and anaplastic lymphoma kinase (ALK). SCLC targeting pathway includes Poly (ADP-ribose) polymerases (PARP) inhibitors, checkpoint kinase 1 (CHK 1) pathway, WEE1 pathway, Ataxia Telangiectasia and Rad3-related (ATR)/Ataxia telangiectasia mutated (ATM), and Delta‐like canonical Notch ligand 3 (DLL-Immune checkpoint inhibitors like programmed cell death protein 1 (PD-1)/ programmed death-ligand 1 (PD-L1) inhibitors and Cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) blockade are also utilized in the management of lung cancer. Many of the targeted therapies are still under development and require clinical trials to establish their safety and efficacy. This review summarizes the mechanism of molecular targets and immune-mediated targets, recently approved drugs, and their clinical trials for lung cancer.
Low frequency ultrasound-assisted drug delivery has been widely investigated as a non-invasive method to enhance the transdermal penetration of drugs. Using this technique, a brief application of ...ultrasound is used to permeabilize skin for a prolonged time. In this review, an overview on ultrasound is detailed to help explain the parameters that could be modulated to obtain the desired ultrasound parameters for enhanced transdermal drug delivery. The mechanisms of enhancement and the latest developments in the area of ultrasound-assisted transdermal drug delivery are discussed. Special emphasis is placed on the effects of ultrasound when used in combination with microneedles, electroporation and iontophoresis, and penetration enhancers. Further, this review summarizes the effect of ultrasound on skin integrity and the regulatory requirements for commercialization of the ultrasound based transdermal delivery instruments.
Buccal mucosal membrane offers an attractive drug-delivery route to enhance both systemic and local therapy. This review discusses the benefits and drawbacks of buccal drug delivery, anatomical and ...physiological aspects of oral mucosa, and various in vitro techniques frequently used for examining buccal drug-delivery systems. The role of mucoadhesive polymers, penetration enhancers, and enzyme inhibitors to circumvent the formulation challenges particularly due to salivary renovation cycle, masticatory effect, and limited absorption area are summarized. Biocompatible mucoadhesive films and patches are favored dosage forms for buccal administration because of flexibility, comfort, lightness, acceptability, capacity to withstand mechanical stress, and customized size. Preparation methods, scale-up process and manufacturing of buccal films are briefed. Ongoing and completed clinical trials of buccal film formulations designed for systemic delivery are tabulated. Polymeric or lipid nanocarriers incorporated in buccal film to resolve potential formulation and drug-delivery issues are reviewed. Vaccine-enabled buccal films have the potential ability to produce both antibodies mediated and cell mediated immunity. Advent of novel 3D printing technologies with built-in flexibility would allow multiple drug combinations as well as compartmentalization to separate incompatible drugs. Exploring new functional excipients with potential capacity for permeation enhancement of particularly large-molecular-weight hydrophilic drugs and unstable proteins, oligonucleotides are the need of the hour for rapid advancement in the exciting field of buccal drug delivery.
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