Pharmaceutical Nanotechnology - Volume 10, Issue 1, 2022

Liposomes have gained attention as a well-accepted nanocarrier for several chemotherapeutic drugs and are considered a drug delivery system of choice for a wide range of products. These amphipathic spherical vesicles primarily consist of one or more phospholipid bilayers, showing promise for drug delivery of both hydrophilic and hydrophobic components in addition to unique properties, such as biocompatibility, biodegradability, low toxicity, and nonimmunogenicity. Recent advances in liposomes are mainly centered on chemical and structural modification with the multifunctional approach to target the cancer cells activating the offensive mechanisms within the proximity of the tumors. Stimuli-responsive liposomes are a precisive approach to deliver and release chemotherapeutic drugs in the tumor site in a controlled fashion, thus reducing damage to normal tissues and preventing the side effects of the conventional chemotherapy regimen. The unique characteristics of the tumor microenvironment facilitate applying an endogenous stimulus (pH, redox potential, or enzymatic activity) to trigger the release of the drug or the application of an external stimulus (heat or light) to tailor the drug release from liposomes. This review focuses on newer developments in stimuli-sensitive liposomal drug delivery systems designed to implement either exogenous (temperature, light, and magnetic field) or endogenous (pH changes, enzymatic triggers, or redox potential) approaches.

Background: Site-specific drug delivery is a widespread and demanding area nowadays. Lipid-based nanoparticulate drug delivery systems have shown promising effects for targeting drugs among lymphatic systems, brain tissues, lungs, and skin. Recently, lipid nanoparticles have been used for targeting the brain via the mucosal route for local therapeutic effects. Lipid nanoparticles (LNPs) can help in enhancing the efficacy and lowering the toxicities of anticancer drugs to treat the tumors, particularly in lymph after metastases of tumors. LNPs contain a nonpolar core that can improve the absorption of lipophilic drugs into the lymph node and treat tumors. Cellular uptake of drugs can also be enhanced using LNPs and therefore, LNPs are the ideal carrier for treating intracellular infections, such as leishmaniasis, tuberculosis and parasitic infection in the brain, etc. Furthermore, specific surface modifications with molecules like mannose, or PEG could improve the macrophage uptake and hence effectively eradicate parasites hiding in macrophages. Methods: An electronic literature search was conducted to update the advancements in the field of site-specific drug delivery utilizing lipid-based nanoparticles. A search of the Scopus database (https://www.scopus.com/home.uri) was conducted using the following keywords: lipid-based nanoparticles; site-specific delivery. Conclusion: Solid lipid nanoparticles have shown site-specific targeted delivery to various organs including the liver, oral mucosa, brain, epidermis, pulmonary and lymphatic systems. These lipidbased systems showed improved bioavailability as well as reduced side effects. Therefore, the focus of this article is to review the recent research studies on LNPs for site-specific or targeting drug delivery.

Background: The brain is a vital and composite organ. By nature, the innate make-up of the brain is such that in anatomical parlance, it is highly protected by the “Blood-Brain Barrier”, which is a nexus of capillary endothelial cells, basement membrane, neuroglial membrane and glialpodocytes. The same barrier, which protects and isolates the interstitial fluid of the brain from capillary circulation, also restricts the therapeutic intervention. Many standing pharmaceutical formulations are ineffective in the treatment of inimical brain ailments because of the inability of the API to surpass and subsist inside the Blood Brain Barrier. Objective: This is an integrated review that emphasizes on the recent advancements in brain-targeted drug delivery utilizing nanodiamonds (NDs) as a carrier of therapeutic agents. NDs are a novel nanoparticulate drug delivery system, having carbon moieties as their building blocks and their surface tenability is remarkable. These neoteric carbon-based carriers have exceptional, mechanical, electrical, chemical, optical, and biological properties, which can be further rationally modified and augmented. Discussion: NDs could be the next“revolution ”in the field of nanoscience for the treatment of neurodegenerative disorders, brain tumors, and other pernicious brain ailments. What sets them apart from other nanocarriers is their versatile properties like diverse size range and surface modification potential, which makes them efficient enough to move across certain biological barriers and offer a plethora of brain targeting and bioimaging abilities. Conclusion: The blood-brain barrier (BBB) poses a major hurdle in the way of treating many serious brain ailments. A range of nanoparticle based drug delivering systems have been formulated, including solid lipid nanoparticles, liposomes, dendrimers, nanogels, polymeric NPs, metallic NPs (gold, platinum, andironoxide) and diamondoids (carbonnanotubes). Despite this development, only a few of these formulations have shown the ability to cross the BBB. Nanodiamonds, because of their small size, shape, and surface characteristics, have a potential in moving beyond the diverse and intricate BBB, and offer a plethora of brain targeting capabilities.

Background: Acne is the pilosebaceous units' disorder. The most important cause of acne is the colonization of bacteria in the follicles. Among antibiotics, doxycycline hyclate kills a wide range of bacteria. Objectives: The study aims to prevent oral administration's side effects, overcome the barriers of conventional topical treatment, and improve the therapeutic effectiveness; this drug was loaded into niosomal nanocarriers for topical application. Methods: Doxycycline hyclate was loaded into four niosomal formulations prepared by the thinfilm hydration method with different percentages of constituents. Drug-containing niosomal systems were evaluated for morphological properties via scanning electron microscopy, particle size, drug entrapment efficiency, zeta potential, in vitro drug release, physical stability after 60 days, in vitro drug permeation through rat skin, in vitro drug deposition in rat skin, toxicity on human dermal fibroblasts (HDF) by MTT method after 72 hours, and antibacterial properties against the main acne-causing bacteria via antibiogram test. Results: The best formulation had the appropriate particle size of 362.88 ± 13.05 nm to target follicles, entrapment efficiency of 56.3 ± 2.1%, the zeta potential of - 24.46±1.39 mV, in vitro drug release of 54.93 ± 1.99% after 32 hours, and the lowest permeation of the drug through the rat skin among all other formulations. Improved cell viability, increased antibacterial activity, and an approximately three-fold increase in drug deposition were the optimal niosomal formulation features relative to the free drug. Conclusion: This study demonstrated the ability of nano-niosomes containing doxycycline hyclate to treat skin acne compared with the free drug.

Introduction: Rosuvastatin calcium (ROSCa) is an anti-hyperlipidemic drug with only 20% oral bioavailability due to its low solubility and high first-pass metabolism. Therefore, the main purpose of this work was to compare solid lipid nanoparticles to nanostructured lipid carriers and evaluate their effect on solubility improvement and hence the bioavailability of a model insoluble drug. Methods: Different nanosuspensions were formulated using high-speed homogenization and ultrasonication techniques, using Apifil as solid lipid and Maisine as liquid lipid. The effect of different variables on quality attributes (particle size, entrapment efficiency (EE), and in vitro release) was studied using the Box-Behnken design. Then, the optimized nanoparticles were lyophilized, filled into capsules, and evaluated. Finally, the optimized formula was clinically evaluated in six healthy human volunteers. Results: It was observed that the variables had a great impact on EE and particle size. Nanoparticles showed maximum particles of 180.3 nm, and % EE ranged from 40.77% to 91.67%. Capsules loaded with NLCs were found to be more stable than those loaded with SLNs. The clinical study of NLCs-ROSCa showed an enhancement in the C max (8.92 ng/ml) compared to the commercial product (2.56 ng/ml) with approximately 349% relative bioavailability. Conclusion: ROSCa was successfully encapsulated in SLNs and NLCs. The optimized NLCs formulation showed improved quality attributes compared to SLNs. Thus, NLCs loaded formulations could be an effective oral drug delivery system to enhance the bioavailability of insoluble drugs.