The Impact of Flavonoid-Loaded Nanoparticles in the UV Protection and Safety Profile of Topical Sunscreens.

Excessive UV radiation exposure is harmful to skin cells since sunburn is accompanied by oxidative burst, leading to a rapid increase in skin cancer. However, the insufficient UV photoprotection of approved sunscreens and the negative impact of their compositions on ecosystems and human health makes the utility of sunscreen a questionable recommendation. Therefore, discovering UV filters with significant antioxidant activity and improved topical performance and photostability is an urgent need. Recently, the use of nanosized natural molecules incorporated in sunscreens has been a scientific hot topic, as it has been suggested that they provide a synergistic effect with synthetic UV filters, improving overall SPF and antioxidant activity, higher retention on the epidermis, and less toxicity. The aim of this review was to verify the usefulness of sunscreens incorporating flavonoid-loaded nanoparticles. A literature review was performed, where original and review articles published in the last 6 years were analyzed. Formulations containing nanosized flavonoids with improved UVA photoprotection and safer toxicological profiles, associated or not with synthetic filters, are promising sunscreens and more clinical investigation must be performed to validate these findings.

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; however, they can disturb the lipid profile of the patients. In this study, self-nanoemulsifying drug delivery systems of omega-3 fatty acids-rich oils are prepared and optimized for the delivery of lipophilic drugs. Rosuvastatin, a potent hypolipidemic drug, was used as a model lipophilic drug. Fish oil showed more than 7-fold higher solubility of rosuvastatin than other oils and therefore it was selected for the development of self-nanoemulsifying drug delivery systems (SNEDDS). Different combinations of surfactants and co-surfactants were screened and a surfactant mixture of Tween 80 (surfactant) and Capryol PGMC (cosurfactant) were selected for compatibility with fish oil and rosuvastatin. A pseudoternary phase diagram of oil, surfactant, and co-surfactant was designed to identify the emulsion region. The pseudoternary phase diagram predicted a 1:3 oil and surfactant mixture as the most stable ratio for the emulsion system. Then, a response-surface methodology (Box-Behnken design) was applied to calculate the optimal composition. After 17 runs, fish oil, Tween 80, and Capryol PGMC in proportions of 0.399, 0.67, and 0.17, respectively, were selected as the optimized formulation. The self-nanoemulsifying drug delivery systems showed excellent emulsification potential, robustness, stability, and drug release characteristics. In the drug release studies, SNEDDS released 100% of the payload in around 6 h whereas, release of the plain drug was less than 70% even after 12 h. Therefore, omega-3 fatty acids-rich healthy lipids have enormous potential to enhance the solubility of lipophilic drugs whereas, self-emulsification can be used as a simple and feasible approach to exploit this potential.

Investigation of Eutectic Mixtures of Fatty Acids as a Novel Construct for Temperature-Responsive Drug Delivery.

Background: 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. Methods: We have developed phase change material, PCM, based on a series of eutectic mixtures of fatty acids due to their unique and attractive physicochemical characteristics such as safety, stability, cost-effectiveness, and ease of availability. The reversible solid-liquid phase transition of PCM is responsible to hold firm or actively release the encapsulated drug. The eutectic mixtures of fatty acids (stearic acid and myristic acid) along with liquid lipid (oleic acid) were prepared to exhibit a tunable thermoresponsive platform. Doxorubicin-loaded lipid nanocarriers were successfully developed with combined hot melt encapsulation (HME) and sonication method and characterized to achieve enhanced permeability and retention (EPR) effect-based solid tumor targeting in response to exogenous temperature stimulus. The cytotoxicity against melanoma cell lines and in vivo safety studies in albino rats was also carried out. Results: Doxorubicin-loaded lipid nanocarriers have a narrow size distribution (94.59-219.3 nm), and a PDI (0.160-0.479) as demonstrated by photon correlation microscopy and excellent colloidal stability (Z.P value: -22.7 to -32.0) was developed. Transmission electron microscopy revealed their spherical morphology and characteristics of a monodispersed system. A biphasic drug release pattern with a triggered drug release at 41°C and 43°C and a sustained drug release was observed at 37°C. The thermoresponsive cytotoxic potential was demonstrated in B16F10 cancer cell lines. Hemolysis assay and acute toxicity studies with drug-free and doxorubicin lipid nanocarrier formulations provided evidence for their non-toxic nature. Conclusion: We have successfully developed a temperature-responsive tunable platform with excellent biocompatibility and intelligent drug release potential. The formulation components being from natural sources present superior characteristics in terms of cost, compatibility with normal body cells, and adaptability to preparation methods. The reported preparation method is adapted to avoid complex chemical processes and the use of organic solvents. The lipid nanocarriers with tunable thermoresponsive characteristics are promising biocompatible drug delivery systems for improved localized delivery of chemotherapeutic agents.

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

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 m2/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 S. aureus, E. coli, and P. aeruginosa 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.

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

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, ex vivo 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. Ex vivo 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.

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

AIMS: The aim of the study is to develop advanced antibacterial agents as nanoparticles instead of antibiotics due to the emergence of antimicrobial resistance. BACKGROUND: Pseudomonas aeruginosa is capable of causing many diseases, including serious bacterial pneumonia. There is a need for an efficient antibacterial agent to kill these pathogens. OBJECTIVE: The objective of the study is the synthesis of advanced antibacterial agents as nanoparticles for biomedical applications that can play a vital role to kill Gram-negative bacteria (Pseudomonas aeruginosa). METHODS: A novel fabrication growth of hydrophilic spiky gold nanoparticles (SGNPs) via reduction method is reported. RESULTS: Surface plasmon resonance peak of the synthesized SGNPs was tuned under near infrared range. The SGNPs have anisotropic and spiky morphology with 68 nm size and -58 mV surface charge and are pure, having adsorption of the organic material. Pseudomonas aeruginosa treated with synthesized SGNPs showed 60% bacterial death at the concentration of 100 µM. CONCLUSION: This work consists of novel synthesis of SGNPs via safe and simple reduction method. The synthesized SGNPs exhibit strong antibacterial activity against the Gram negative bacteria Pseudomonas aeruginosa measured using microplate assay test. The result showed that these SGNPs are ideal for biomedical applications.

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

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.

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

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.

Folate targeted lipid chitosan hybrid nanoparticles for enhanced anti-tumor efficacy.

Folic acid is often used for active targeting of tumor cells to enhance therapeutic outcomes. Here, folic acid was conjugated with chitosan and folate-conjugated chitosan-lipid hybrid nanoparticles were prepared by ionic gelation method using anionic lipid. These nanoparticles were in size range of 200 to 400 nm with spherical shape. In vitro drug release data suggested a sustained release of cisplatin. The therapeutic efficacy of the folate-conjugated hybrid nanoparticles was evaluated in SK-OV-3, A2780 and MCF-7 cancer cell lines. A significant increase in cytotoxicity was observed with folate targeted LPHNPs compared to non-targeted LPHNPs. Significantly enhanced cellular uptake and cell cycle arrest resulting from folate-targeted nanoparticles were confirmed using fluorescence microscopy and flow cytometry. The therapeutic efficacy and tumor penetration were further evaluated in 3D spheroid tumor models. These studies suggest that folate-conjugated lipid-chitosan nanoparticles could enhance therapeutic activity and may represent a promising platform for active targeting of tumor cells.

Lipid-polymer hybrid nanoparticles for controlled delivery of hydrophilic and lipophilic doxorubicin for breast cancer therapy.

Background: Lipid polymer hybrid nanoparticles (LPHNPs) for the controlled delivery of hydrophilic doxorubicin hydrochloride (DOX.HCl) and lipophilic DOX base have been fabricated by the single step modified nanoprecipitation method. Materials and methods: Poly (D, L-lactide-co-glicolide) (PLGA), lecithin, and 1,2-distearoyl-Sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000 (DSPE-PEG 2000) were selected as structural components. Results: The mean particle size was 173-208 nm, with an encapsulation efficiency of 17.8±1.9 to 43.8±4.4% and 40.3±0.6 to 59. 8±1.4% for DOX.HCl and DOX base, respectively. The drug release profile was in the range 33-57% in 24 hours and followed the Higuchi model (R2=0.9867-0.9450) and Fickian diffusion (n<0.5). However, the release of DOX base was slower than DOX.HCl. The in vitro cytotoxicity studies and confocal imaging showed safety, good biocompatibility, and a higher degree of particle internalization. The higher internalization of DOX base was attributed to higher permeability of lipophilic component and better hydrophobic interaction of particles with cell membranes. Compared to the free DOX, the DOX.HCl and DOX base loaded LPHNPs showed higher antiproliferation effects in MDA-MB231 and PC3 cells. Conclusion: Therefore, LPHNPs have provided a potential drug delivery strategy for safe, controlled delivery of both hydrophilic and lipophilic form of DOX in cancer cells.

Ionically Cross-Linked Chitosan Nanoparticles for Sustained Delivery of Docetaxel: Fabrication, Post-Formulation and Acute Oral Toxicity Evaluation.

INTRODUCTION: Polymeric nanoparticles are potential carriers for the efficient delivery of hydrophilic and hydrophobic drugs due to their multifaceted applications. Docetaxel is relatively less hydrophobic and twice as potent as paclitaxel. Like other taxane chemotherapeutic agents, docetaxel is not well tolerated and shows toxicity in the patients. Nanoencapsulation of potent chemotherapeutic agents has been shown to improve tolerability and therapeutic outcome. Therefore, the present study was designed to fabricate chitosan and sodium tripolyphosphate (STPP) based on ionically cross-linked nanoparticles for sustained release of docetaxel. METHODS: Nanoparticles were prepared by the ionic-gelation method by dropwise addition of the STPP solution into the chitosan solution in different ratios. CNPs were characterized for post-formulation parameters like size, zeta potential, scanning electron microscope (SEM), FTIR, DSC/TGA, pXRD, and in-vitro drug release, as well as for acute oral toxicity studies in Wistar rats. RESULTS AND DISCUSSION: The optimized docetaxel loaded polymeric nanoparticles were in the size range (172.6nm-479.65 nm), and zeta potential (30.45-35.95 mV) required to achieve enhanced permeation and retention effect. In addition, scanning electron microscopy revealed rough and porous surface, whereas, FTIR revealed the compatible polymeric nanoparticles. Likewise, the thermal stability was ensured through DSC and TG analysis, and powder X-ray diffraction analysis exhibited solid-state stability of the docetaxel loaded nanoparticles. The in-vitro drug release evaluation in phosphate buffer saline (pH 7.4) showed sustained release pattern, i.e. 51.57-69.93% within 24 hrs. The data were fitted to different release kinetic models which showed Fickian diffusion as a predominant release mechanism (R2 = 0.9734-0.9786, n= 0.264-0.340). Acceptable tolerability was exhibited by acute oral toxicity in rabbits and no abnormality was noted in growth, behavior, blood biochemistry or histology and function of vital organs. CONCLUSION: Ionically cross-linked chitosan nanoparticles are non-toxic and biocompatible drug delivery systems for sustained release of chemotherapeutic agents, such as docetaxel.

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

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.

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

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.

Enhancement of Dissolution and Skin Permeability of Pentazocine by Proniosomes and Niosomal Gel.

Proniosomes (PN) are the dry water-soluble carrier systems that may enhance the oral bioavailability, stability, and topical permeability of therapeutic agents. The low solubility and low oral bioavailability due to extensive first pass metabolism make Pentazocine as an ideal candidate for oral and topical sustained release delivery. The present study was aimed to formulate the PNs by quick slurry method that are converted to niosomes (liquid dispersion) by hydration, and subsequently formulated to semisolid niosomal gel. The PNs were found in spherical shape in the SEM and stable in the physicochemical and thermal analysis (FTIR, TGA, and XRD). The quick slurry method produced high recovery (> 80% yield) and better flow properties (θ = 28.1-37.4°). After hydration, the niosomes exhibited desirable entrapment efficiency (44.45-76.23%), size (4.98-21.3 µm), and zeta potential (- 9.81 to - 21.53 mV). The in vitro drug release (T100%) was extended to more than three half-lives (2-4 h) and showed good fit to Fickian diffusion indicated by Korsmeyer-Peppas model (n = 0.136-0.365 and R2 = 0.9747-0.9954). The permeation of niosomal gel was significantly enhanced across rabbit skin compared to the pure drug-derived gel. Therefore, the PNs are found promising candidates for oral as dissolution enhancement and sustained release for oral and topical delivery of pentazocine for the management of cancer pain.

Graphene-based nanocomposites: synthesis and their theranostic applications.

Graphene, the mother of all carbon materials, has unlocked a new era of biomedical nanomaterials due to its exceptional biocompatibility, physicochemical and mechanical properties. It is a single atom thick, nanosized, two-dimensional structure and provides high surface area with adjustable surface chemistry to form hybrids. The present article provides a comprehensive review of ever-expanding application of graphene nanomaterials with different inorganic and organic materials in drug delivery and theranostics. Methods of preparation of nanomaterials are elaborated and biological and physicochemical characteristics of biomedical relevance are also discussed. Graphene form nanomaterials with metallic nanoparticles offer multiscale application. First, graphene act as a platform to attach nanoparticles and provide excellent mechanical strength. Second, graphene improves efficacy of metallic nanoparticles in diagnostic, biosensing, therapeutic and drug delivery application. Graphene-based polymeric nanocomposites find wider application in drug delivery with flexibility to incorporate hydrophilic, hydrophobic, sensitive and macromolecules. In addition, grapheme quantum dots and graphene hybrids with inorganic nanocrystal and carbon nanotubes hybrids have shown interesting properties for diagnosis and therapy. Finally, we have pointed out research trends that may be more common in future for graphene-based nanomaterials.

The era of biofunctional biomaterials in orthopedics: what does the future hold?

INTRODUCTION: Titanium-based materials do not fulfill all of the requirements of orthopedic implants due to a mismatch in mechanical properties with bone which are prone to change during the course of bone growth. Biofunctional biomaterials are a new class of materials that show bioactivity and adaptability at any stage of bone growth. AREAS COVERED: Different biofunctional biomaterials have evolved over time that can enhance calcium phosphate (CaP) precipitation, stimulate osteogenic differentiation, and can control osteoblast gene expression. These materials include metals or metal alloys, ceramics, polymers and biocomposites. Similarly, naturally-inspired nanomaterials and nanometer surface featured modified materials can enhance bone growth if created to match bone's unique micro to nano hierarchical structure. Nanoscale manipulation of existing biomaterials can incorporate antimicrobial properties which is desirable to prevent infection and failure of orthopedic devices. EXPERT COMMENTARY: Recent research trends in biofunctional biomaterials have focused to, first, understand the bone growth mechanism and, then, mimic natural bone architecture using biomaterials. Therefore, an enhanced understanding of material properties and tissue engineering principles will lead the way forward designing biofunctional biomaterials. In the future, the role of biofunctional biomaterials and orthopedic sensors will be more pronounced in terms of musculoskeletal disease prevention, diagnosis, and treatment.

Solid lipid nanoparticles for thermoresponsive targeting: evidence from spectrophotometry, electrochemical, and cytotoxicity studies.

Thermoresponsive drug delivery systems are designed for the controlled and targeted release of therapeutic payload. These systems exploit hyperthermic temperatures (>39°C), which may be applied by some external means or due to an encountered symptom in inflammatory diseases such as cancer and arthritis. The objective of this paper was to provide some solid evidence in support of the hypothesis that solid lipid nanoparticles (SLNs) can be used for thermoresponsive targeting by undergoing solid-liquid phase transition at their melting point (MP). Thermoresponsive lipid mixtures were prepared by mixing solid and liquid natural fatty acids, and their MP was measured by differential scanning calorimetry (DSC). SLNs (MP 39°C) containing 5-fluorouracil (5-FU) were synthesized by hot melt encapsulation method, and were found to have spherical shape (transmission electron microscopy studies), desirable size (<200 nm), and enhanced physicochemical stability (Fourier transform infrared spectroscopy analysis). We observed a sustained release pattern (22%-34%) at 37°C (5 hours). On the other hand, >90% drug was released at 39°C after 5 hours, suggesting that the SLNs show thermoresponsive drug release, thus confirming our hypothesis. Drug release from SLNs at 39°C was similar to oleic acid and linoleic acid nanoemulsions used in this study, which further confirmed that thermoresponsive drug release is due to solid-liquid phase transition. Next, a differential pulse voltammetry-based electrochemical chemical detection method was developed for quick and real-time analysis of 5-FU release, which also confirmed thermoresponsive drug release behavior of SLNs. Blank SLNs were found to be biocompatible with human gingival fibroblast cells, although 5-FU-loaded SLNs showed some cytotoxicity after 24 hours. 5-FU-loaded SLNs showed thermoresponsive cytotoxicity to breast cancer cells (MDA-MB-231) as cytotoxicity was higher at 39°C (cell viability 72%-78%) compared to 37°C (cell viability >90%) within 1 hour. In conclusion, this study presents SLNs as a safe, simple, and effective platform for thermoresponsive targeting.

Development and optimization of methotrexate-loaded lipid-polymer hybrid nanoparticles for controlled drug delivery applications.

Lipid-polymer hybrid nanoparticles (LPHNPs) are emerging platforms for drug delivery applications. In the present study, methotrexate loaded LPHNPs consisted of PLGA and Lipoid S100 were fabricated by employing a single-step modified nanoprecipitation method combined with self-assembly. A three factor, three level Box Behnken design using Design-Expert® software was employed to access the influence of three independent variables on the particle size, drug entrapment and percent drug release. The optimized formulation was selected through numeric optimization approach. The results were supported with the ANOVA analysis, regression equations and response surface plots. Transmission electron microscope images indicated the nanosized and spherical shape of the LPHNPs with fair size distribution. The nanoparticles ranged from 176 to 308nm, which increased with increased polymer concentration. The increase in polymer and lipid concentration also increased the drug entrapment efficiency. The in vitro drug release was in range 70.34-91.95% and the release mechanism follow the Higuchi model (R2=0.9888) and Fickian diffusion (n<0.5). The in vitro cytotoxicity assay and confocal microscopy of the optimized formulation demonstrate the good safety and better internalization of the LPHNPs. The cell antiproliferation showed the spatial and controlled action of the nanoformulation as compared to the plain drug solution. The results suggest that LPHNPs can be a promising delivery system envisioned to safe, stable and potentially controlled delivery of methotrexate to the cancer cells to achieve better therapeutic outcomes.

Non-invasive strategies for targeting the posterior segment of eye.

The safe and effective treatment of eye diseases has been remained a global myth. Several advancements have been done and various drug delivery and treatment techniques have been suggested. The Posterior segment disorders are the leading cause of visual impairments and blindness. Targeting the therapeutic agents to the anterior and posterior segments of the eye has attracted extensive attention from the scientific community. Significant key factors in the success of ocular therapy are the development of safe, effective, economic and non-invasive novel drug delivery systems. These specialized non-invasive ocular drug delivery systems revolutionized the drug delivery strategies by overcoming the limitations, provided targeted delivery to the ocular tissues by avoiding larger doses, and reducing the toxicity encountered by the conventional approaches. These non-invasive systems are fabricated by ingredients encompassing biodegradability, biocompatibility, mucoadhesion, solubility and permeability enhancement and stimuli responsiveness. The variety of routes are utilized to provide minimally invasive drug delivery to the patients without any discomfort and pain. This review is focused on the brief introduction, types, significance, preparation techniques, components and mechanism of drug release of non-invasive systems, including in situ gelling systems, microspheres, iontophoresis, nanoparticles, nanosuspensions and specialized novel emulsions.