Self-Nanoemulsification of Healthy Oils to Enhance the Solubility of Lipophilic Drugs

The low aqueous solubility of many drugs reduces their bioavailability in the blood. Oils have been used for centuries to enhance the solubility of drugs; ...

Quaid-I-Azam University

The oral delivery of cancer chemotherapeutic drugs is challenging due to low bioavailability, gastrointestinal side effects, first-pass metabolism and P-glycoprotein efflux pumps. Thus, chemotherapeutic drugs, including Docetaxel, are administered via an intravenous route, which poses many disadvantages of its own. Recent advances in pharmaceutical research have focused on designing new and efficient drug delivery systems for site-specific targeting, thus leading to improved bioavailability and pharmacokinetics. A decent number of studies have been reported for the safe and effective oral delivery of Docetaxel. These nanocarriers, including liposomes, polymeric nanoparticles, metallic nanoparticles, hybrid nanoparticles, dendrimers and so on, have shown promising results in research papers and clinical trials. The present article comprehensively reviews the research efforts made so far in designing various advancements in the oral delivery of Docetaxel. Different strategies to improve oral bioavailability, prevent first-pass metabolism and inhibition of efflux pumping leading to improved pharmacokinetics and anticancer activity are discussed. The final portion of this review article presents key issues such as safety of nanomaterials, regulatory approval and future trends in nanomedicine research.

Advancements in the oral delivery of Docetaxel: challenges, current state-of-the-art and future trends.

Despite of the remarkable cytotoxic and imaging potential of ultra-small metal nanoclusters, their toxicity-free and targeted delivery to cancerous cells remains a substantial challenge that hinders their clinical applications. In this study, a polymeric scaffold was first synthesized by grafting folic acid and thiol groups to chitosan (CS) for cancer cell targeting and improved gastric permeation. Furthermore, silver nanocluster (Ag NCs) were synthesized in situ, within CS scaffold by microwave irradiation and core-shell nanocapsules (NCPs) were prepared with hydrophobic docetaxel (DTX) in the core and Ag NCs embedded CS in the shell. A significant cytotoxicity synergism (~300 folds) was observed for DTX with co-delivery of Ag NCs against breast cancer MDA-MB-231 cells. Following oral administration, the DTX-Ag-NCPs increased bioavailability due to enhanced drug transport across gut (9 times), circulation half-life (~6.8 times) and mean residence time (~6.7 times), as compared to the control DTX suspension. Moreover, 14 days acute oral toxicity of the DTX-Ag-NCPs was performed in mice and evaluated for changes in blood biochemistry parameters, organ to body weight index and histopathology of liver and kidney tissues that revealed no significant evidence of toxicity suggesting the safety and efficiency of the DTX-Ag-NCPs as hybrid nanocarrier for biocompatible delivery of metal nanoclusters.

Polymeric nanocapsules embedded with ultra-small silver nanoclusters for synergistic pharmacology and improved oral delivery of Docetaxel.

Increasing drift in antimicrobial therapy failure against Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), and the advent of extended resistant strains strongly demand discovery of mechanisms underlying development of drug resistance. The emergence of resistance against anti-TB drugs has reached an alarming level in various parts of the world, providing an active platform for the design of new targeted drug delivery. Reactive oxygen species (ROS) have an important role in controlling TB pathogenesis. At macrophage activation, ROS that are produced inside macrophages directly kill resident bacteria. These ROS possess a dual character because they can kill macrophages along with the resident bacteria. Targeting these ROS can play a remarkable part in overcoming resistance of conventional drugs. Nanoparticles (NPs) have evolved as a potential drug carrier for targeted delivery and elimination of various resistance mechanisms against antimicrobials. Receptor-mediated targeting of macrophages via different NPs may be a promising strategy for combating drug resistance and enhancing efficacy of old-fashioned antimycobacterial agents.

Tuberculosis Resistance and Nanoparticles: Combating the Dual Role of Reactive Oxygen Species in Macrophages for Tuberculosis Management.

The aim of the study is to develop advanced antibacterial agents as nanoparticles instead of antibiotics due to the emergence of antimicrobial resistance.

Facile and Novel Synthesis of Spiky Gold Nanoparticles as an Efficient Antimicrobial Agent against Pseudomonas Aeruginosa.

Nanotheranostics is an emerging frontier of personalized medicine research particularly for cancer, which is the second leading cause of death. Supramolecular aspects in theranostics are quite allured to achieve more regulation and controlled features. Supramolecular nanotheranostics architecture is focused on engineering of modular supramolecular assemblies benefitting from their mutable and stimuli-responsive properties which confer an ultimate potential for the fabrication of unified innovative nanomedicines with controlled features. Amalgamation of supramolecular approaches to nano-based features further equip the potential of designing novel approaches to overcome limitations seen by the conventional theranostic strategies, for curing even the lethal diseases and endowing personalized therapeutics with optimistic prognosis, endorsing their clinical translation. Among many potential nanocarriers for theranostics, lipid nanoparticles (LNPs) have shown various promising advances in theranostics and their formulation can be tailored for several applications. Despite the great advancement in cancer nanotheranostics, there are still many challenges that need to be highlighted to fill the literature gap. For this purpose, herein, we have presented a systematic overview on the subject and proposed LNPs as the potential material to manage cancer via non-invasive approaches by highlighting the use of supramolecular approaches to make them robust for cancer theranostics. We have concluded the review by entailing the future perspectives of lipid nanotheranostics towards clinical translation.

Supramolecular lipid nanoparticles as delivery carriers for non-invasive cancer theranostics.

In this article, formulation studies for terbinafine hydrochloride nanoemulsions, prepared by high-energy ultrasonication technique, are described. Pseudo-ternary phase diagram was constructed in order to find out the optimal ratios of oil and surfactant/co-solvent mixture for nanoemulsion production. Clove and olive oils were selected as oil phase. Based on the droplet size evaluation, maximum nanoemulsion region were determined for formulation development. Further characterization included polydispersity index (PDI), zeta potential, Fourier transform infrared (FT-IR) spectroscopy, morphology, pH, viscosity, refractive index,  skin permeation, skin irritation, and histopathological examination. Droplet sizes of optimized formulations were in colloidal range. PDI values below 0.35 indicated considerably homogeneous nanoemulsions. Zeta potential values were from 13.2 to 18.1 mV indicating good stability, which was also confirmed by dispersion stability studies.  permeation studies revealed almost total skin permeation of terbinafine hydrochloride from the nanoemulsions (96-98%) in 6 hours whereas commercial product reached only 57% permeation at the same time. Maximum drug amounts were seen in epidermis and dermis layers. Skin irritation and histopathological examination demonstrated dermatologically safe formulations. In conclusion, olive oil and clove oil-based nanoemulsion systems have potential to serve as promising carriers for topical terbinafine hydrochloride delivery.

Olive oil and clove oil-based nanoemulsion for topical delivery of terbinafine hydrochloride:  and  evaluation.

The continuing growth of bacterial resistance makes the top challenge for the healthcare system especially in bone-infections treatment. Current estimates reveal that in 2050 the death ratio caused by bacterial infections can be higher than cancer. The aim of this study is to provide an alternative to currently available bone-infection treatments. Here we designed mesoporous hydroxyapatite nanocarriers functionalized with citrate (Ctr-mpHANCs). Amoxicillin (AMX) is used as a model drug to load in Ctr-mpHANCs, and the drug loading was more than 90% due to the porous nature of nanocarriers. Scanning electron microscopy shows the roughly spherical morphology of nanocarriers, and the DLS study showed the approximate size of 92 nm. The Brunauer-Emmett-Teller (BET) specific surface area and pore diameter was found to be about 182.35 m/g and 4.2 nm, respectively. We noticed that almost 100% of the drug is released from the AMX loaded Ctr-mpHANCs (AMX@Ctr-mpHANCs) in a pH-dependent manner within 3 d and 5 d at pH 2.0 and 4.5, respectively. The sustained drug release behaviour was observed for 15 d at pH 7.4 and no RBCs hemolysis by AMX@Ctr-mpHANCs. The broth dilution and colony forming unit (CFU) assays were used to determine the antimicrobial potential of AMX@Ctr-mpHANCs. It was observed in both studies that AMX@Ctr-mpHANCs showed a significant reduction in the bacterial growth of , , and  as compared to Ctr-mpHANCs with no bacteria-killing. Thus, we proposed that Ctr-mpHANCs can be used as a drug carrier and a treatment option for bone infections caused by bacteria.

Synthesis and Characterization of Antibiotic-Loaded Biodegradable Citrate Functionalized Mesoporous Hydroxyapatite Nanocarriers as an Alternative Treatment for Bone Infections.

Most of the traditional nanocarriers of cancer therapeutic moieties present dose-related toxicities due to the uptake of chemotherapeutic agents in normal body cells. The severe life-threatening effects of systemic chemotherapy are well documented. Doxorubicin, DOX is the most effective antineoplastic agent but with the least specific action that is responsible for severe cardiotoxicity and myelosuppression that necessitates careful monitoring while administering. Stimuli-sensitive/intelligent drug delivery systems, specifically those utilizing temperature as an external stimulus to activate the release of encapsulated drugs, have become a subject of recent research. Thus, it would be ideal to have a nanocarrier comprising safe excipients and controllable drug release capacity to deliver the drug at a particular site to minimize unwanted and toxic effects of chemotherapeutics. We have developed a simple temperature-responsive nanocarrier based on eutectic mixture of fatty acids. This study aimed to develop, physicochemically characterize and investigate the biological safety of eutectic mixture of fatty acids as a novel construct for temperature-responsive drug release potential.

Mubashar Rehman

Department of Pharmacy

Quaid-I-Azam University

Self-Nanoemulsification of Healthy Oils to Enhance the Solubility of Lipophilic Drugs

Mubashar Rehman

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Pharmacy

Quaid-I-Azam University

Self-Nanoemulsification of Healthy Oils to Enhance the Solubility of Lipophilic Drugs

Department of Pharmacy