Drug delivery systems for the topical treatment of cutaneous leishmaniasis

Introduction: The parenteral administration of pentavalent antimonials for the treatment of all forms of leishmaniasis, including cutaneous leishamniasis (CL), has several limitations. Therapy is long, requiring repeated doses and the adverse reactions are frequent. Topical treatment is an attractive alternative for CL, offering significant advantages over systemic therapy: fewer adverse effects, ease of administration, and lower costs.

Areas covered: This review covers, from 1984 to the present, the progress achieved for the development of topical treatment for CL, using different drugs such as paromomycin (PA), imiquimod, amphotericin B (AmB), miltefosine, and buparvaquone. PA is the most commonly studied drug, followed by AmB and Imiquimod. These drugs were incorporated in conventional dosage forms or loaded in lipid nanocarries, which have been used mainly for improved skin delivery and antileishmanial activity.

Expert opinion: Developing an effective topical treatment for CL using these antileishmanial drugs still remains a great challenge. Insights into the most promising delivery strategies to improve treatment of CL with PA and AmB using conventional dosage forms, lipid nanocarriers, and combined therapy are presented and discussed. The results obtained with combined therapy and alternative delivery systems are promising perspectives for improving topical treatment of CL.     

Lymphatic system: a prospective area for advanced targeting of particulate drug carriers

Introduction: The lymphatic system has a critical role in the immune system's recognition and response to disease and it is an additional circulatory system throughout the entire body. Extensive multidisciplinary investigations have been carried out in the area of lymphatic delivery, and lymphatic targeting has attracted a lot of attention for providing preferential chemotherapy and improving bioavailability of drugs that undergo hepatic first-pass metabolism.

Areas covered: This review focuses on progress in the field of lymphatic therapeutics and diagnosis. Moreover, the anatomy and physiology of the lymphatic system, particulate drug carriers and different physicochemical parameters of both modified and unmodified particulate drug carriers and their effect on lymphatic targeting are addressed.

Expert opinion: Particulate drug carriers have encouraged lymphatic targeting, but there are still challenges in targeting drugs and bioactives to specific sites, maintaining desired action and crossing all the physiological barriers. Lymphatic therapy using drug-encapsulated lipid carriers, especially liposomes and solid lipid nanoparticles, emerges as a new technology to provide better penetration into the lymphatics where residual disease exists. Size is the most important criteria when designing nanocarriers for targeting lymphatic vessels as the transportation of these particles into lymphatic vessels is size dependent. By increasing our understanding of lymphatic transport and uptake, and the role of lymphatics in various diseases, we can design new therapeutics for effective disease control.     

Recent trends in cancer drug resistance reversal strategies using nanoparticles

Introduction: Resistance to chemotherapy is a major obstacle in the successful amelioration of tumors in many cancer patients. Resistance is either intrinsic or acquired, involving mechanisms such as genetic aberrations, decreased influx and increased efflux of drugs. Strategies for the reversal of resistance involve the alteration of enzymes responsible for drug resistance, the modulation of proteins regulating apoptosis mechanisms and improving the uptake of drugs using nanotechnology. Novel strides in the reversal of drug resistance are emerging, involving the use of nanotechnology, targeting stem cells, etc.

Areas covered: This paper reviews the most recent cancer drug reversal strategies involving nanotechnology for targeting cancer cells and cancer stem cells (CSCs), for enhanced uptake of micro- and macromolecular inhibitors.

Expert opinion: Nanotechnology used in conjunction with existing therapies, such as gene therapy and P-glycoprotein inhibition, has been shown to improve the reversal of drug resistance; the mechanisms involved in this include specific targeting of drugs and nucleotide therapeutics, enhanced cellular uptake of drugs and improved bioavailability of drugs with poor physicochemical characteristics. Important strategies in the reversal of drug resistance include: a multifunctional nanoparticulate system housing a targeting moiety; therapeutics to kill resistant cancer cells and CSCs; cytotoxic drugs and a tumor microenvironment stimuli-responsive element, to release the encapsulated therapeutics.     

Nanocarrier systems for delivery of siRNA to ovarian cancer tissues

Introduction: Novel therapeutic strategies have been investigated for ovarian cancer to reduce toxicity and to improve outcomes for patients. Short interfering RNA (siRNA), which directs the sequence-specific degradation of target mRNA and provides specificity of gene knockdown, represents a unique class of potential therapeutics for ovarian cancer. However, siRNA molecules are rapidly degraded in plasma and are unable to passively diffuse through cellular membranes. Nanocarriers can efficiently protect siRNA from in vivo degradation and are able to deliver these active macromolecules to tumor cells even after intravenous administration.

Areas covered: Strategies of gene therapy and the role of siRNA in ovarian cancer treatment are introduced, followed by an overview of nanocarriers for siRNA delivery, the advantages of the systems and the types of targeting to tumor cells. Classes of nanocarriers for delivery of siRNA, their functionalities and modalities are discussed with emphasis on the promising vehicles.

Expert opinion: Gene silencing therapy based on siRNA represents a possible opportunity for treatment of ovarian cancer patients. However, this approach requires selection of suitable nanocarriers that can safely and effectively deliver siRNA to the target site to induce its effect. Very little work has been done in this field; therefore, it is a good direction for future development.     

The use of quantitative analysis and Hansen solubility parameter predictions for the selection of excipients for lipid nanocarriers to be loaded with water soluble and insoluble compounds

The aim of these studies was to determine the miscibility of different API with lipid excipients to predict drug loading and encapsulation properties for the production of solid lipid nanoparticles and nanostructured lipid carriers. Five API exhibiting different physicochemical characteristics, viz., clarithromycin, efavirenz, minocycline hydrochloride, mometasone furoate, and didanosine were used and six solid lipids in addition to four liquid lipids were investigated. Determination of solid and liquid lipids with the best solubilization potential for each API were performed using a traditional shake-flask method and/or a modification thereof. Hansen solubility parameters of the API and different solid and liquid lipids were estimated from their chemical structure using Hiroshi Yamamoto’s molecular breaking method of Hansen Solubility Parameters in Practice software. Experimental results were in close agreement with solubility parameter predictions for systems with ΔδT < 4.0 MPa^1/2. A combination of Hansen solubility parameters with experimental drug-lipid miscibility tests can be successfully applied to predict lipids with the best solubilizing potential for different API prior to manufacture of solid lipid nanoparticles and nanostructured lipid carriers.     

In vivo study of mPEG–PCL as a nanocarriers for anti-inflammatory drug delivery of simvastatin

Purpose: In this study, methoxy poly (ethylene glycol)-poly (ε-caprolactone) (mPEG–PCL) di-block copolymers were synthesized. The purpose of this work is to investigate the in vivo anti-inflammatory effects of simvastatin-loaded micelles.

Methods: The structure of synthesized copolymers was characterized by using HNMR, FTIR, and GPC techniques. Simvastatin was encapsulated in micelles through a single-step nano-precipitation method, leading to the formation of simvastatin-loaded mPEG–PCL (simvastatin-mPEG–PCL) micelles. In this study, the anti-inflammatory effects of simvastatin/mPEG–PCL micelles versus indomethacin were investigated in acute inflammation-induced rats. The paw edema thickness was measured 1, 2, 3, and 4?h after injection of formulation. The inhibition of edema in various groups were calculated and reported by percentages.

Results: The results showed that the zeta potential of micelles was about ?14.9?±?0.47?mV and the average size was in range of 66.10?±?0.34?nm. Simvastatin was encapsulated in mPEG–PCL micelles with a loading capacity of 9.63?±?0.87% and an encapsulation efficiency of 64.20?±?0.79%. Simvastatin and simvastatin-mPEG–PCL micelles showed significant anti-inflammatory activity in the present study.

Conclusions: This study revealed that simvastatin and simvastatin/mPEG–PCL micelles both have anti-inflammatory effects and suggested that statins have potential anti-inflammatory activity along with their lipid lowering properties.     

纳米药物载体在中药制剂研发中的应用

纳米药物载体通常由天然或合成高分子材料制成，大小在10～1 000 nm ，因其具有靶向性、缓释性、载体材料可生物相容和降解等显著优点，已在药物制剂研发中得到广泛应用。近年来，中药纳米制剂发展迅速，作者通过查阅国内外文献，重点围绕毫微粒、脂质纳米粒、纳米乳、纳米胶束、纳米脂质体等几种典型的纳米载体的特性、制备及其在中药制剂研发中的应用进行综述。     

Preparation,Characterization, and Anticancer Effects of Capsaicin-Loaded Nanoliposomes

Background: Medicinal plants have proven their value as a source of molecules with therapeutic potential, and recent studies have shown that capsaicin has profound anticancer effects in several types of human cancers. However, its clinical use is handicapped due to its poor pharmacokinetics. This study aims to enhance capsaicin’s pharmacokinetic properties by loading the molecule into nanoliposomes model and testing its anticancer activity. Methods: Nanoliposomes were prepared using the thin-film method, and characteristics were examined followed by qualitative and quantitative analyses of encapsulation efficiency and drug loading using HPLC at different lipid/capsaicin ratios. Cell viability assay (MTT) was used to determine IC₅₀. Results: Capsaicin-loaded nanoliposomes showed optimum characteristics of morphology, particle size, zeta potential, and stability. In vitro anticancer activity of capsaicin and capsaicin-loaded nanoliposomes were compared against MCF7, MDA-MB-231, K562, PANC1, and A375 cell lines. Capsaicin-loaded nanoliposomes showed significant improvement in anticancer activity against cancers cell lines studied (p < 0.001), with increased selectivity against cancer cells compared to capsaicin. Conclusion: The encapsulated capsaicin nanoliposomes produced an improvement in pharmacokinetics properties, enhancing the anticancer activity and selectivity compared with capsaicin. This model seems to offer a potential for developing capsaicin formulations for the prevention and treatment of cancer.     

Development of Encapsulation Strategies and Composite Edible Films to Maintain Lactoferrin Bioactivity: A Review

Lactoferrin (LF) is a whey protein with various and valuable biological activities. For this reason, LF has been used as a supplement in formula milk and functional products. However, it must be considered that the properties of LF can be affected by technological treatments and gastrointestinal conditions. In this article, we have revised the literature published on the research done during the last decades on the development of various technologies, such as encapsulation or composite materials, to protect LF and avoid its degradation. Multiple compounds can be used to conduct this protective function, such as proteins, including those from milk, or polysaccharides, like alginate or chitosan. Furthermore, LF can be used as a component in complexes, nanoparticles, hydrogels and emulsions, to encapsulate, protect and deliver other bioactive compounds, such as essential oils or probiotics. Additionally, LF can be part of systems to deliver drugs or to apply certain therapies to target cells expressing LF receptors. These systems also allow improving the detection of gliomas and have also been used for treating some pathologies, such as different types of tumours. Finally, the application of LF in edible and active films can be effective against some contaminants and limit the increase of the natural microbiota present in meat, for example, becoming one of the most interesting research topics in food technology.