Current Drug Delivery - Volume 18, Issue 3, 2021

In recent years, SLNs and NLCs are among the popular drug delivery systems studied for the delivery of lipophilic drugs. Both systems have demonstrated several beneficial properties as an ideal drug-carrier, optimal drug-loading, and good long-term stability. NLCs are getting popular due to their stability advantages and the possibility to load various oil components either as an active or as a matrix. This review screens types of oils used till date in combination with solid lipids to form NLCs. These oils are broadly classified into two categories: Natural oils and Essential oils. NLCs offer range of advantages in drug delivery due to the formation of an imperfect matrix owing to the presence of oil. The type and percentage of oil used, determine optimal drug loading and stability. Literature shows that a variety of oils is/are used in NLCs mainly as the matrix, which is from natural origin, triglycerides class. On the other hand, essential oils not only serve as a matrix but also as an active moiety. In short, oil is the key ingredient in the formation of NLCs, hence it needs to be selected wisely as per the performance criteria expected. The aim of this article is to discuss shortly the role of liquid lipids and highlight the use of variety of oils in NLCs preparation.

Diabetes mellitus is one of the long-known chronic diseases. Today, over 400 million people have been diagnosed with diabetes, yet curing it is still a challenge. Over the decades, the approaches of treating diabetes mellitus have evolved and polymeric materials have played an integral part in developing and manufacturing anti-diabetic medications. However, injection of insulin remains a conventional therapy for the treatment of diabetes. Oral administration is generally the most preferred route; yet, physiological barriers lead to a challenge in the formulation development for oral delivery of antidiabetic peptide and protein drugs. This present review focuses on the role of different types of biodegradable polymers (e.g., synthetic and natural) that have been used to develop micro and nanoparticles based formulations for anti-diabetic drugs (Type 1 and Type 2) and how the various encapsulation strategies impact its therapeutic effect, including pharmacokinetics studies, drug release profiles, and efficacy of the encapsulated drugs. This review also includes studies of different dosage forms such as oral, nasal, inhalation, and sublingual for the treatment of diabetes that have been investigated using synthetic and natural biodegradable polymers in order to develop an alternative route to subcutaneous route for better control of serum glucose levels.

The Coronavirus disease 2019 (COVID-19) has found its roots from Wuhan (China). COVID-19 is caused by a novel coronavirus SARS-CoV2, previously named as 2019-nCoV. It has spread across the globe and was declared as a pandemic by the World Health Organization (WHO) on 11th March, 2020. Currently, there is no standard drug or vaccine available for the treatment, therefore, repurposing of existing drugs is the only solution. Novel Drug Delivery Systems (NDDS) will be boon for the repurposing of drugs. The role of various NDDS in repurposing of existing drugs for the treatment of various viral diseases and their relevance in COVID-19 has been discussed in this paper. It focuses on the currently ongoing research in the implementation of NDDS in COVID-19. Moreover, it describes the role of NDDS in vaccine development for COVID-19. This paper also emphasizes how NDDS will help to develop the improved delivery systems (dosage forms) of existing therapeutic agents and also explore the new insights to find out the void spaces for potential targeted delivery. Therefore, in these tough times, NDDS and nanotechnology can be a safeguard to humanity.

Background: Development of controlled drug delivery systems can improve the pharmacokinetic characteristics of drug molecules in the human body, thereby significantly improving the utilization rate of drugs and reducing toxicity and side effects caused by their high concentrations, which can occur when delivery is not controlled. Metal organic frameworks are a new class of very promising crystalline microporous materials, especially when the size is reduced to the nanometer range. Metal-organic frameworks exhibit large specific surface areas, tunable compositions, and easy functionalization. In recent years, an increasing number of studies have reported the remarkable advances in multifunctional nanoscale metal-organic frameworks in drug delivery. Objective: To review the latest research involving advances in stimuli-responsive nanoscale metal organic frameworks as drug delivery systems in controlled-release drugs. Discussion: We first introduce the two main strategies associated with nanoscale metal organic frameworks used in drug loading: direct assembly and post-encapsulation. We next focus on the latest discoveries of nanoscale metal-organic framework-based stimulus response systems for drug delivery, including pH, magnetics, light, ion, temperature, and other stimuli, as well as multiple stimulus- responsive drug delivery systems. Finally, we discuss the challenges and future developmental directions of nanoscale metal-organic framework-based controlled drug release.

Introduction: Bioconjugations are swiftly progressing and are being applied to solve several limitations of conventional Drug Delivery Systems (DDS) such as lack of water solubility, non-specific, and poor bioavailability. The main goals of DDS are to achieve greater drug effectiveness and minimize toxicity to the healthy tissues. Objectives and Methods: In this study, D-glucose was conjugated with eugenol to target the cancer cells. To identify the implication of the anticancer effect, osteosarcoma (K7M2) cells were cultured and the anti-proliferative effect was performed using MTT [3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyl tetrazolium bromide assay] test in order to evaluate the viability and toxicity on cells with various concentrations of eugenol and D-glucose-eugenol conjugate in 24-hour incubation. Results: It was found that, the successful confirmation of the conjugation between D-glucose and eugenol was obtained by 1H NMR spectroscopy. MTT assay showed inhibitory concentration (IC50 value) of D-glucose-eugenol was at 96.2 μg/ml and the decreased of osteosarcoma cell survival was 48%. Conclucion: These findings strongly indicate that K7M2 cells would be affected by toxicity of Dglucose- eugenol. Therefore, the present study suggests that D-glucose-eugenol has high potential to act as an anti-proliferative agent who may promise a new modality or approach as the drug delivery treatment for cancer or chemotherapeutic agent.

Background: Mesoporous Bioactive Glass (MBG) has been widely studied because of its excellent histocompatibility and degradability. However, due to the lack of good osteoinductive activity, the pure MBG scaffold is not effective in repairing large-scale bone defects. Objective: To observe the repair effect of MBG scaffolds delivering Salvianolic acid B (SB) on critical bone defects in rats. Methods: In this study, MBG scaffolds were used as delivery vehicle. SB, a small molecular active drug with good osteogenic differentiation ability, was loaded into the MBG scaffolds at low, medium and high doses. The effect of SB released from the MBG scaffolds on osteogenic differentiation of rat Bone Marrow Mesenchymal Stem Cells (rBMSCs) was investigated using alkaline phosphatase staining, alizarin red staining and real-time quantitative polymerase chain reaction. Moreover, 8 weeks after implantation of the scaffolds, the bone regeneration was evaluated by micro- CT, sequential fluorescence labeling and histological staining analysis. Results: The in vitro results showed that different doses of SB had similar release rate from scaffolds and could be released from scaffolds continuously. The middle dose (MBG/MSB) and high dose (MBG/HSB) groups significantly promoted the osteogenic differentiation of rBMSCs when compared with a low dose (MBG/LSB) group. Moreover, SB produced significant increases in newly formed bone of calvarial bone defects in rats. Conclusion: It is concluded that the use of MBG scffolds delivering SB is an effective strategy for the treatment of bone defects.

Aim: The synthesis of seven new antioxidant agents based on the combination of thiazole, pyridine, triazole and pyrazole moieties. The studies of their antioxidant activity using DPPH reduction method. The DFT analysis of the 7 ligands. The docking study was also investigated. The better binding affinity with α-cyclodextrin as best drug delivery system. Background: The screening of new antioxidant compounds and find the good mechanism for binding sites, with correlating between experience and computer theory. Objectives: The DFT analysis of the 7 synthesized ligands.The docking study was also investigated by using the amino acids Ala167 and Arg172. The better binding affinity with α-cyclodextrin as best drug delivery system. Methods: The studies of their antioxidant activity using DPPH reduction method. Results: Chemistry: synthesis of 7 ligands by condensation reaction with 89% yield. Antioxidant activities using DPPH reduction with a good value IC50=13.05 ± 3.73 μg/ml. Using DFT (EHOMO and ELUMO) and Docking APX with the amino acids Ala167 and Arg172 compared to the ascorbic acid. Correlation between all these properties. α-cyclodextrin as best drug delivery system (better binding affinity than caffeic acid). Conclusion: For the drug delivery study, The ACD is best system for all the compounds due to the smallest cavity size which makes the binding affinities favorable and possible to prepare prospective nano-antioxidants.

Background: Essential oils are considered as promising sources of novel anticancer compounds. Carvacrol (CVC), the major constituent of many aromatic plants including oregano and thymus, is endowed with curative properties on different cancers, including liver, colon, and lung. Little information is available regarding the potential of CVC for the treatment of brain cancers, notably Glioblastoma Multiforme (GBM). Objective: In this work, we investigated the in vitro effect of CVC codrugs (CVC1-8), synthesized by direct-coupled co-drug strategies, on human glioblastoma cell line (U87-MG) for the first time. Methods: Cell viability was detected by MTT and LDH assays while expression levels of important genes (such as EGFR, NFKB1A, AKT1, AKT2, and others) associated with GBM and inflammatory pathways were detected by PCR array. Results: Results showed that CVC1-8 codrugs induced cytotoxicity and positive alterations in molecular responses on U87MG cells. Particularly, important pathways (such as PI3K/PTEN/AKT) involved in the onset and progression of GBM resulted in modulation by CVC3 and CVC8. Conclusion: Our results suggest that CVC3 and CVC8 could be suitable candidates for further investigation to develop new strategies for the prevention and/or treatment of GBM.

Purpose: The purpose of this study is to develop a new PLGA based formulation for microspheres, which aims to release mometasone furoate for one month, so as to improve compliance. Methods: The microspheres containing mometasone furoate were prepared by oil in water emulsion and solvent evaporation. The microspheres were characterized by surface morphology, shape, size and encapsulation efficiency. The release in vitro was studied in 37°C phosphate buffer, and in vivo, pharmacodynamics and preliminary safety evaluation were conducted in male Sprague Dawley rats. Results: The morphology results showed that the microspheres have a smooth surface, spherical shape and an average diameter of 2.320-5.679μm. The encapsulation efficiency of the microspheres loaded with mometasone furoate was in the range of 53.1% to 95.2%, and the encapsulation efficiency of the microspheres could be greatly affected by the proportion of oil phase to the water phase and other formulation parameters. In vitro release kinetics revealed that drug release from microspheres was through non-Fick's diffusion and PLGA polymer erosion. Pharmacokinetic data showed that the initial release of microspheres was small and then sustained. The results of the pharmacodynamics study fully proved the long-term effectiveness of mometasone furoate microspheres. The results of in vivo safety evaluation showed that the preparation system possessed good in vivo safety. Conclusion: This study shows that the microspheres prepared in this study have sufficient ability to stable drug release at least for 35 days, with good efficacy and high safety. In addition, mometasone furoate can be used as a potential candidate drug for 35 days long-term injection.

Aim: To design D-Mannose conjugated 5-Fluorouracil (5-FU) loaded Jackfruit Seed Starch Nanoparticles (JFSSNPs) for site-specific delivery. Background: Liver cancer is the third leading cause of death in the world and the fifth most often diagnosed cancer. It is a major global threat to public health. Treatment of liver cancer with conventional method bears several side effects, thus to undertake these side effects as a formulation challenge, it is necessary to develop novel target-specific drug delivery system for the effective and better localization of drug into the proximity of target with restricting the movement of the drug in normal tissues. Objective: To optimize and characterize the developed D-Mannose conjugated 5-Fluorouracil (5- FU) loaded Jackfruit Seed Starch Nanoparticles (JFSSNPs) for effective treatment of liver cancer. Materials and Methods: 5-FU loaded JFSSNPs were prepared and optimized formulations having higher encapsulation efficiency were conjugated with D-Mannose. These formulations were characterized for size, morphology, zeta potential, X-Ray Diffraction, and Differential Scanning Calorimetry. The potential of NPs was studied using in vitro cytotoxicity assay, in vivo kinetic studies, and bio-distribution studies. Result and Discussion: 5-Fluorouracil loaded NPs had a particle size between 336 to 802 nm with drug entrapment efficiency between 64.2 to 82.3%. In XRD analysis, 5-FU peak was diminished in the diffractogram, which could be attributed to the successful incorporation of the drug in amorphous form. DSC study suggests there was no physical interaction between 5-FU and Polymer. NPs showed sustained in vitro 5-FU release up to 2 hours. In vivo, mannose conjugated NPs prolonged the plasma level of 5-FU and assisted in the selective accumulation of 5-FU in the liver (vs. other organs spleen, kidney, lungs, and heart) compared to unconjugated one and plain drug. Conclusion: In vivo, bio-distribution, and plasma profile studies resulted in a significantly higher concentration of 5-Fluorouracil liver, suggesting that these carriers are efficient, viable, and targeted carrier of 5-FU treatment of liver cancer.