Pharmaceutical Nanotechnology - Volume 7, Issue 2, 2019

Massive data available on cancer therapy more than ever lead our mind to the general concept that there is no perfect treatment for cancer. Indeed, the biological complexity of this disease is too excessive to be treated by a single therapeutic approach. Current delivery systems containing a specific drug or gene have their particular opportunities and restrictions. It is worth noting that a considerable number of studies suggest that single- drug delivery systems result in insufficient suppression of cancer growth. Therefore, one of the main ideas of co-delivery system designing is to enhance the intended response or to achieve the synergistic/combined effect compared to the single drug strategy. This review focuses on various strategies for co-delivery of therapeutic agents in the treatment of cancer. The primary approaches within the script are categorized into co-delivery of conventional chemotherapeutics, gene-based molecules, and plant-derived materials. Each one is explained in examples with the recent researches. In the end, a brief summary is provided to conclude the gist of the review.

Diabetes is a group of diseases characterized by hyperglycemia and originating from the deficiency or resistance to insulin, or both. Ultimately, the most effective treatment for patients with diabetes involves subcutaneous injections of insulin. However, this route of administration is often painful and inconvenient, as most patients will have to selfadminister it at least twice a day for the rest of their lives. Also, infection, insulin precipitation, and either lipoatrophy or lipohypertrophy are frequently observed at the site of injection. To date, several alternative routes of insulin administration have been explored, including nasal, pulmonary and oral. Although the delivery of insulin is an ideal route for diabetic patients, several limitations have to be overcome such as the rapid degradation of insulin in gastric fluid and low oral bioavailability. Numerous strategies have been carried out to improve these limited parameters such as the use of enzyme inhibitors, absorption enhancers, mucoadhesive polymers and chemical modification for receptor-mediated absorption. Also, insulin-loaded nanocarriers bypass several physiological barriers. This current review focuses on the various barriers existing in the delivery of insulin through the oral route and the strategies undertaken so far to overcome those obstacles using nanocarriers as a potential vehicle of insulin.

In the past decades, nanomaterials have shown great potential in biomedical fields, especially in drug delivery, imaging and targeted therapy. Recently, the development of novel functional nanomaterials for antibacterial application has attracted much attention. Compared to the traditional direct use of antibiotics, antibacterial nanomaterials either as drug delivery systems or active agents have a higher efficacy and lower side effects. Herein, we will focus on the antibacterial applications of four commonly used nanomaterials, including metal-based nanomaterials, polymeric nanoparticles, graphene oxides or carbon-based nanomaterials and nanogels.

Background: Miniaturization of nanosuspensions preparation is a necessity in order to enable proper formulation screening before nanosizing can be performed on a large scale. Ideally, the information generated at small scale is predictive for large scale production. Objective: This study was aimed to investigate the scalability when producing nanosuspensions starting from a 10 g scale of nanosuspension using low energy wet ball milling up to production scales of 120 g nanosuspension and 2 kg nanosuspension by using a standard high energy wet ball milling operated in batch mode or recirculation mode, respectively. Methods: Two different active pharmaceutical ingredients, i.e. curcumin and hesperetin, have been used in this study. The investigated factors include the milling time, milling speed, and the type of mill. Results: Comparable particle sizes of about 151 nm to 190 nm were obtained for both active pharmaceutical ingredients at the same milling time and milling speed when the drugs were processed at 10 g using low energy wet ball milling or 120 g using high energy wet ball milling in batch mode, respectively. However, an adjustment of the milling speed was needed for the 2 kg scale produced using high energy wet ball milling in recirculation mode to obtain particle sizes comparable to the small scale process. Conclusion: These results confirm in general, the scalability of wet ball milling as well as the suitability of small scale processing in order to correctly identify the most suitable formulations for large scale production using high energy milling.

Objective: To circumvent the aforementioned problems and for the successful delivery of those newly discovered poorly soluble compounds, researchers have focused on the feasibility of biocompatible lipids such as Solid lipid nanoparticles (SLN) as carrier system. Background: Sertraline (SRT) is commercially available as hydrochloride salt. Poor bioavailability (around 44%) of hydrochloride salt is considered to be conversion of salts to free base in the gastrointestinal tract which retard it’s absorption. Methods: Different batches of solid lipid nanoparticles (SLN) were prepared and on the basis of particle size, polydispersity index (PDI), zeta potential (ZP), encapsulation efficiency (EE), and drug loading capacity (L) an optimum system was designed. Results: The optimized formulation contains; 5% (w/v) Compritol® E ATO as lipids, 2.5% (w/v) Tween® 80 as surfactant and 0.1% (w/v) SRT as actives. The formulation was freeze-dried using mannitol as a cryoprotectant to control the aggregation of particles during redispersion process. SLN with <110 nm size, <0.2 PDI, >36 mV ZP, >72% EE, and nearly 0.7% L can be formed at appropriate formulation process conditions; homogenization time (HT) and sonication time (ST) at 5 min and 10 min, respectively. XRD studies indicated the presence of amorphous form of drug that is completely encapsulated within the nanoparticulate matrix system. The optimized SLN formulation have shown the highest value of zeta potential (-36.5 mV) confers stability of nanodispersion. Release of drug encapsulated in SLN showed a biphasic pattern and was extended upto 12 hours. The maximum plasma concentration (Cmax) and area under the curve (AUC) in case of sertraline loaded SLN were found 10-fold and 6-fold higher, respectively compared to pure drug. Conclusion: The result depicted enhanced extent of absorption of sertraline from SLN compared to plain sertraline. Furthermore, sertraline-loaded SLN were found to be stable at 4°C for 6 months of study period. Hence, the SLN can be used as a potential carrier for successful delivery of poorly water-soluble drugs associated with poor oral bioavailability like sertraline.