Current Pharmaceutical Design - Volume 24, Issue 43, 2018

Growing interest in the field of nanotechnology has led to its emergence in the field of medicine too. Nanomedicines encompass the various medical tools, diagnostic agents and the drug delivery vehicles being evolved with the advancements in the aura of nanotechnology. This review emphasizes on providing a cursory literature on the past events that led to the procession of nanomedicines, various novel drug delivery systems describing their structural features along with the pros and cons associated with them and the nanodrugs that made a move to the clinical practice. It also focuses on the need of the novel drug delivery systems and the challenges faced by the conventional drug delivery systems.

Background: The therapeutic approaches for the management of topical infections have always been a difficult approach due to lack of efficacy of conventional topical formulations, high frequency of topical applications and non-patient compliance. The major challenge in the management of topical infections lies in antibiotic resistance which leads to severe complications and hospitalizations resulting in economic burden and high mortality rates. Methods: Topical delivery employing lipid-based carriers has been a promising strategy to overcome the challenges of poor skin permeation and retention along with large doses which need to be administered systemically. The use of lipid-based delivery systems is a promising strategy for the effective topical delivery of antibiotics and overcoming drug-resistant strains in the skin. The major systems include transfersomes, niosomes, ethosomes, solid lipid nanoparticles, nanostructured lipid carriers, microemulsion and nanoemulsion as the most promising drug delivery approaches to treat infectious disorders. The main advantages of these systems include lipid bilayer structure which mimics the cell membrane and can fuse with infectious microbes. The numerous advantages associated with nanocarriers like enhanced efficacy, improvement in bioavailability, controlled drug release and ability to target the desired infectious pathogen have made these carriers successful. Conclusion: Despite the number of strides taken in the field of topical drug delivery in infectious diseases, it still requires extensive research efforts to have a better perspective of the factors that influence drug permeation along with the mechanism of action with regard to skin penetration and deposition. The final objective of the therapy is to provide a safe and effective therapeutic approach for the management of infectious diseases affecting topical sites leading to enhanced therapeutic efficacy and patient-compliance.

Approximately 40 % drugs in the market are having poor aqueous solubility related problems and 70 % molecules in discovery pipeline are being practically insoluble in water. Nanocrystals is a prominent tool to solve the issue related to poor aqueous solubility and helps in improving the bioavailability of many drugs as reported in the literature. Nanocrystals can be prepared by top down methods, bottom up methods and combination methods. Many patented products such as Nanocrystals®, DissoCubes®, NANOEDGE® and SmartCrystals ®, etc., are available, which are based on these three preparation methodologies. The particle size reduction resulted into unstable nanocrystalline system and the phenomenon of Ostawald ripening occurs. This instability issue could be resolved by using an appropriate stabilizers or combination of stabilizers. The nanosuspensions could be transformed to the solid state to prevent particle aggregation in liquid state by employing various unit operations such as lyophilisation, spray drying, granulation and pelletisation. These techniques are well known for their scalability and continuous nanocrystal formation advantages. Nanocrystals can be characterized by using scanning electron microscopy, transmission electron microscopy, atomic force microscopy, differential scanning calorimetry, fourier transform infrared spectroscopy, powdered x- ray diffraction and photon correlation spectroscopy. The downscaling of nanocrystals will enable rapid optimization of nanosuspension formulation in parallel screening design of preclinical developmental stage drug moieties. One of the most acceptable advantages of nanocrystals is their wide range of applicability such as oral delivery, ophthalmic delivery, pulmonary delivery, transdermal delivery, intravenous delivery and targeting (brain and tumor targeting). The enhancement in market value of nanocrystals as well as the amount of nanocrystal products in the market is gaining attention to be used as an approach in order to get commercial benefits.

Despite the fact that protein and peptide therapeutics are widely employed in the treatment of various diseases, their delivery is posing an unembellished challenge to the scientists. It was discovered that delivery of these therapeutic systems through oral route is easy with high patient compliance. However, proteolytic degradation and absorption through the mucosal epithelium are the barriers in this route. These issues can be minimized by the use of enzyme inhibitors, absorption enhancers, different carrier systems or either by direct modification. In the process of investigation, it was found that transdermal route is not posing any challenges of enzymatic degradation, but, still absorption is the limitation as the outer layer of skin acts as a barrier. To suppress the effect of the barrier and increase the rate of the absorption, various advanced technologies were developed, namely, microneedle technology, iontophoresis, electroporation, sonophoresis and biochemical enhancement. Indeed, even these molecules are targeted to the cells with the use of cell-penetrating peptides. In this review, delivery of the peptide and protein therapeutics using oral, transdermal and other routes is discussed in detail.

Background: Peptide nucleic acids (PNAs) belong to the next generation of synthetic nucleic acid analogues. Their high binding affinity and specificity towards the target DNA or RNA make them the reagent of choice for gene therapy-based applications. Objective: To review important gene therapy based applications of regular and chemically modified peptide nucleic acids in combination with nanotechnology. Method: Selective research of the literature. Results: Poor intracellular delivery of PNAs has been a significant challenge. Among several delivery strategies explored till date, nanotechnology-based strategies hold immense potential. Recent studies have shown that advances in nanotechnology can be used to broaden the range of therapeutic applications of PNAs. In this review, we discussed significant advances made in nanoparticle-based on PLGA polymer, silicon, oxidized carbon and graphene oxide for the delivery of PNAs. Conclusion: Nanoparticles delivered PNAs can be implied in diverse gene therapy based applications including gene editing as well as gene targeting (antisense) based strategies.

The properties of nanoparticles can be exploited to overcome challenges in drug delivery. By virtue of its design and size, the pharmacokinetics of nanoparticles are different than other small molecules. Modeling and simulation techniques have great potential to be used in nanoformulation development; however, their use in optimization of nanoformulation is very limited. This review highlights the differences in absorption, distribution, metabolism and excretion (ADME) characteristics of nanoparticles, use of modeling and simulation techniques in nanoformulation development and challenges in the implementation of modeling techniques.

Background: Gallic acid (GA-3,4,5-trihydroxybenzoic acid), a phenolic phytochemical, is a ubiquitous secondary metabolite found in most plants, with appreciable concentrations in grapes seed, rose flowers, sumac, oak and witch hazel. GA often results from the hydrolysis of terpenes and the polyphenol tannic acid. Applications: It exhibits powerful antioxidant, anti-inflammatory, antimicrobial, and anti-cancer activities. Most intriguing benefit has been reported to be on the skin. Due to these beneficial properties, GA and its derivatives (e.g. lipid-soluble phenols such as synthetic gallic esters aka gallates) have been extensively used as an adjuvant in a number of therapeutic formulations, as a substitute of hydrocortisone in children with atopic dermatitis (AD) and other skin conditions (hyperpigmentation, wound healing), and as a cosmetic ingredient. GA has a USFDA GRAS status (generally recognized as safe), exhibiting fairly low systemic toxicity and associated mortality at acute doses in many experimental models. Despite anti-skin aging benefits obtained with relatively safe GA formulations, few cases of gallate-induced skin allergic have been reported in humans. Therefore, approaches to improve the bioavailability and biodegradability of this poor-water soluble and non-biodegradable phenolic compound are warranted. Purpose: This review has focused on the recently reported biological activities pertaining to the skin as well as the pharmacological properties of GA and its derivatives with special emphasis on its use in (nano-) cosmetic formulations. Since this is an evolving area of research, an adequate emphasis has been placed upon advantages and disadvantages of various nanoformulations.

Background: The usage of natural biomaterials or naturally derived materials intended for interface with biological systems has steadily increased in response to the high demand of amenable materials, which are suitable for purpose, biocompatible and biodegradable. There are many naturally derived polymers which overlap in terms of purpose as biomaterials but are equally diverse in their applications. Methods: This review examines the applications of the following naturally derived polymers; hyaluronic acid, silk fibroin, chitosan, collagen and tamarind polysaccharide (TSP); further focusing on the biomedical applications of each as well as emphasising on individual novel applications. Results: Each of the polymers was found to demonstrate a wide variety of successful biomedical applications fabricated as wound dressings, scaffolds, matrices, films, sponges, implants or hydrogels to suit the therapeutic need. Interestingly, blending and amelioration of polymer structures were the two selection strategies to modify the functionality of the polymers to suit the purpose. Further, these polymers have shown promise to deliver small molecule drugs, proteins and genes as nano-scale delivery systems. Conclusion: The review highlights the range of applications of the aforementioned polymers as biomaterials. Hyaluronic acid, silk fibroin, chitosan, collagen and TSP have been successfully utilised as biomaterials in the subfields of implant enhancement, wound management, drug delivery, tissue engineering and nanotechnology. Whilst there are a number of associated advantages (i.e. biodegradability, biocompatibility, non-toxic, nonantigenic as well as amenability) the selected disadvantages of each individual polymer provide significant scope for their further exploration and overcoming challenges like feasibility of mass production at a relatively low cost.

Background: In spite of considerable efforts of researchers the cancer deseases remain to be incurable and a percentage of cancer deseases in the structure of mortality increases every year. At that, high systemic toxicity of antitumor drugs hampers their effective use. Because of this fact, the development of nanosystems for targeted delivery of antitumor drugs is one of the leading problem in nanomedicine and nanopharmacy. Objective: To critically examine the modern strategies for carbon nanotubes (CNTs)-based delivery of anticancer quinones and to summarize the mechanisms which can provide high effectiveness and multifunctionality of the CNT-based quinone delivery platform. Results: Quinones, including anthracycline antibiotics – doxorubicin and daunorubicin, are among the most prospective group of natural and syntetic compounds which exhibit high antitumor activity against different type of tumors. In this review, we focus on the possibilities of using CNTs for targeted delivery of antitumor compounds with quinoid moiety which is ordinarily characterized by high specific interaction with DNA molecules. Quinones can be non-covalently adsorbed on CNT surface due to their aromatic structure and π-conjugated system of double bonds. The characteristic features of doxorubicine-CNT complex are high loading efficiency, pH-dependent release in acidic tumor microenviroment, enough stability in biological fluid. Different types of CNT functionalization, targeting strategies and designs for multifunctional CNT-based doxorubicine delivery platform are disscussed. Conclusion: Nanosystems based on functionalized CNTs are very promising platform for quinone delivery resulting in significant enhancement of cancer treatment efficiency. Functionalization of CNTs with the polymeric shell, especially DNA-based shells, can provide the greatest affinity and mimicry with biological structures.

Background : Nanotechnology has been one of the most prominent forefront grounds in several traditional research areas of science and technology, and development of medicines at nanoscale can be reflected by the tremendous surge in market interest. Present outlook: Its applications include various research areas of medicine, drug delivery technology, diagnostic devices, tissue engineering and gene therapy. Along with immense advances, this technology comes with major limitations including potential immune reactivity and complex characterization of these products. Regulatory challenges: The lack of a proper regulatory perspective due to infidelities in scientific findings have led to further uncertainties and vagueness of the nanoscale domain, particularly its safety implications. Guideline scenario: Early development pathways and regulations should be a top-notch priority to help researchers fail faster and more economically. This would facilitate the peaking utility of these materials in medicine without compromising public health and environmental integrity. This review attempts to emphasize the regulatory rationales of key considerations in nanotechnology along with a portray of the present scenario.