Current Nanomedicine - Volume 10, Issue 3, 2020

Background: The development of modern medical and pharmaceutical science has garnered lots of attention due to the development of targeted therapy and precision medicine. The current focus of the researchers is on developing strategies which provide the maximum therapeutic benefits with minimal adverse effects. In this scenario, nanostructured lipid carriers (NLC) have gained prominence because of their ability to improve the therapeutic properties of the drugs. Objective: In this review, we focus on some of the important methods involved in the preparation and characterization of the NLCs. We also discuss the application of NLC as a drug delivery system through different routes of administration and its role in overcoming the physiological and anatomical barriers. Methods: The literature was collected from different scientific browsers like sciencedirect, google scholar, pubmed and a total of 155 articles were read and analysed for the content. Results: The NLC improve the solubility and bioavailability of the drug, prolong the release and residence time and delay clearance. They also protect the drugs from enzymatic degradation and allow them to pass through different anatomical and physiological barriers. Conclusion: Though the use of NLCs has been reported across different therapeutic indications through various routes of administration, this success at the laboratory level has not gone to the next stage. One of the reasons for the failure of NLC formulations to progress to the next level could be due to toxicity caused by the accumulation of NLCs in organs. Hence, in order to utilize this strategy to its maximum potential, further research is inevitable.

Background: The high molecular weight and increasing lipophilicity of drug face many problems starting from the drug development to formulation and conduction of pharmacological, toxicological and pharmacokinetic studies to its biological application. To overcome this problem, nano-sized formulations are in trend recently. The use of Solid lipid nanoparticles (SLNs) offers new insight into the formulation of the poor soluble and low bioavailable drug. Objective: The study aimed to investigate the literature concerning the development of SLNs for oral drug delivery of poorly soluble drugs, with a view survey the various methods of manufacturing and evaluation of formulation of SLNs and future prospects of SLNs and application of SLNs in oral delivery systems. Conclusion: Oral drug delivery is looking ahead progressively into newer directions due to the realization of various poor performance limiting factors such as reduced drug solubility or absorption, rapid metabolism, high actuation in plasma level of drug and variability caused due to food effect. These play a vital role in disappointing in vivo results, which leads in the failure of the conventional delivery system. Since the last decade, oral drug delivery has taken a new dimension with the increasing application of SLNs as a carrier for the delivery of poorly water-soluble or lipophilic drugs. The site-specific and sustained release effect of the drug is better achieved by using SLNs. This review highlights the various pros and cons, manufacturing techniques, characterization, and future prospects of SLNs in oral drug delivery systems.

Inflammatory Bowel Disease (IBD) is a disorder of the gastrointestinal tract, which is characterized by Crohn’s disease and Ulcerative colitis. Ulcerative colitis (UC) is a chronic idiopathic relapsing colon disease distinguishes by the interference of epithelial wall and colonic site tenderness. For the treatment of ulcerative colitis, various side effects have been reported, due to the non-specific delivery of the targeted drug of the conventional system. This review will explain the reader about various considerations for the preparation of orally administered NPs drug delivery systems for the treatment of ulcerative colitis. Moreover, principles and novel strategies for colon targeting based on the physiology of colon so that the tract of gastro intestine can be used as the identification marker for a target site for drugs. Besides this, the role of phytomedicines in controlling and managing the ulcerative colitis has been discussed. Additionally, the major problem for the smart delivery of NPs in clinical applications with their difficulties in Intellectual Property Rights (IPR) was also discussed. Finally, this review provides various potential approaches to NPs for the treatment of UC.

In the last few decades, researchers and pharmaceutical industries have been developing new approaches to overcome the solubility and bioavailability limits observed with poorly soluble drugs. With the advancement of nanotechnology, nanocrystals have emerged as a great potential to overcome these limitations. Nanocrystals owing to its ability to modify the physicochemical and biological properties of the drug have gained widespread attention among the research scientists. This review provides comprehensive detail on the associated advantages, challenges, factors affecting physicochemical properties, and optimization parameters about the stability of nanocrystals. In this review, the evolution of nanocrystals is discussed as first-generation simple nanocrystals, secondgeneration nanocrystals within a carrier, and third-generation surface-modified nanocrystals. It also provides a detailed account of various preparation methods and evaluation of surface-modified nanocrystals. In the proposed "King Design," nanocrystals of the third generation are placed on the top due to their advantage over other nanocarriers like high drug payload, site-specific delivery, improved activity, commercial manufacturing, and easy scale-up. Third generations nanocrystals can provide a novel therapeutic solution for the site-specific, targeted, and efficient delivery for treatment of various acute as well as chronic diseases with high stability and scale-up potential.

Objectives: Acyclovir (ACV) is an antiviral drug, which requires frequent dosing regimen because of poor oral bioavailability and short half-life. In this study, ACV nanoparticles were formulated using ammonium methacrylates copolymers such as Eudragit RS 100 (Eud RS) and Eudragit RL 100 (Eud RL) to prolong release drug, and increase bioavailability. Methods: ACV loaded nanoparticles were prepared by the solvent replacement technique and then were characterized by particle size, distribution, entrapment efficiency, differential scanning calorimeter, transmission electron microscope, and in-vitro drug release. Results: It was found that as drug:polymer ratio changed from 1:2 to1:5, particle size and drug entrapment efficiency increased significantly. ACV– Eud RS loaded nanoparticles had a larger mean diameter of 363 nm in comparison to 200 nm of ACV- Eud RL nanoparticles. DSC results showed that in the prepared ACV-Eud RS nanoparticles, the drug was presented in the amorphous phase and may have been molecularly dispersed in the polymer matrix, but in the ACV-Eud RL nanoparticles, the drug was presented in the particles and homogeneously dispersed in the polymeric matrix. The entrapment efficiency of AVC-Eud RS nanoparticles was higher than that of ACV-Eud RL nanoparticles. In vitro drug release study showed that the ratios of released drug from ACV-Eud RS nanoparticles in the range from 58±3.8 to 62.9±4.6%, which was lower than those from ACV-Eud RL nanoparticles, in the range from 73.3±4.9 to 77.9±2.9%. The release was found to follow the Weibull model with a Fickian diffusion mechanism for both ACVEud RS and ACV- Eud RL nanoparticles. Conclusion: These results suggest that ACV nanoparticles based on Eud RS100 and Eud RL100 could prolong the release of the drug.

Background: Glioblastoma multiforme (GBM) is a belligerent brain tumor constituting about 67% of primary brain tumours. The current therapy for glioblastoma multiforme is surgery, radiations and chemotherapy though the success rate is quite limited. Azacitidine is a hydrophilic anti-cancer agent which acts by demethylation and is used in the treatment of both acute and chronic myelomonocytic leukaemia along with GBM. Objective: Formulation of stable Azacitidine loaded poly-lactide-co-glycolide (PLGA) nanoparticles (NPs) with tailor-made release profiles. Methods: Preparation of Azacitidine loaded PLGA nanoparticles was done by double emulsion (w/o/w) solvent evaporation technique. PLGA was used in the formulation, as it is biocompatible and biodegradable. Polyvinyl alcohol worked as an emulsifier while Span 80 decreased the interfacial tension among two immiscible phases (aqueous and organic), resulting in increased stability of the formulation. Results: Polymer concentration was directly proportional to the entrapment and drug loading and inversely proportional to particle size. Azacitidine loaded PLGA NPs showed a biphasic release model. At the first stage, burst release was observed, followed by sustained release. About 43.93 ± 0.69% drug was released in 1 hour and the remaining drug was released in 48 hours. Conclusion: Dual release behavior first delivered an ample amount of dose which provided cytotoxic dose, followed by the maintenance dose for sustaining the cytotoxic drug levels. Future prospective requires In-vitro cell viability evaluation of tailor-made polymeric nanoparticles along with In-vivo evaluation for therapeutic intervention in a glioblastoma tumor model.

Introduction: Diabetes mellitus is one of the most important health issues worldwide. The rising incidence of the disease has resulted in a parallel increase of complications such as diabetic foot ulcers (DFU). It is estimated that 25% of patients with diabetes will develop foot ulcers over a lifetime. In Mexico, this lifetime incidence is about 40% to 50%, and 20% of the cases will require amputations. DFU can result in staggering financial burdens for the healthcare system and the patient. Therapies that promote rapid and complete healing and reduce the need for expensive surgical procedures would impact these costs substantially. Methods: Cu/TiO2–SiO2 nanoparticles were synthesized by T. López et al. sol-gel patented method. After synthesis, they were characterized using transmission electron microscopy (TEM) and X-ray diffraction. Then, they were embedded in a polymeric gel matrix. The Cu/TiO2–SiO2 nanogel was used as conservative therapy for a chronic non-healing DFU on a 62-year old female with several comorbidities and chronic complications of diabetes. Wound debridement was performed prior to nanogel administration. The nanogel was applied over the ulcer on alternate days for an initial period of 2 weeks and then continued for 10 months. Results: Significant improvement was observed in the wound healing process since the first applications. The infection was limited and tissue regeneration was enhanced until complete healing of the ulcer. Conclusion: Cu/TiO2–SiO2 nanogel therapy enhanced reepithelialization and healing of the DFU. The successful outcome allowed to avoid the amputation that was proposed for the patient.