Photothermal Effect and Multi-Modality Imaging of Up-Conversion Nanomaterial Doped with Gold Nanoparticles.

Two key concerns exist in contemporary cancer chemotherapy in clinics: limited therapeutic efficiency and substantial side effects in patients. In recent years, researchers have been investigating revolutionary cancer treatment techniques and photo-thermal therapy (PTT) has been proposed by many scholars. A drug for photothermal cancer treatment was synthesized using the hydrothermal method, which has a high light-to-heat conversion efficiency. It may also be utilized as a clear multi-modality bioimaging platform for photoacoustic imaging (PAI), computed tomography (CT), and magnetic resonance imaging (MRI). When compared to single-modality imaging, multi-modality imaging delivers far more thorough and precise details for cancer diagnosis. Furthermore, gold-doped upconverting nanoparticles (UCNPs) have an exceptionally high target recognition for tumor cells. The gold-doped UCNPs, in particular, are non-toxic to normal tissues, endowing the as-prepared medications with outstanding therapeutic efficacy but exceptionally low side effects. These findings may encourage the creation of fresh effective imaging-guided approaches to meet the goal of photothermal cancer therapy.

Evaluation of hyaluronic acid nanoparticle embedded chitosan-gelatin hydrogels for antibiotic release.

The development of chitosan-gelatin (CS-G) hydrogels embedded with ampicillin-loaded hyaluronic acid nanoparticles (HA-NPs) for wound dressing is proposed. It was aimed to provide controlled ampicillin delivery by incorporation of HA-NPs into biocompatible CS-G hydrogel structure. According to in vitro ampicillin release studies, 55% of ampicillin was released from CS-G/HA-NPs hydrogels after 5 days. Antibacterial performance of CS-G/HA-NPs hydrogels was proven with agar disc diffusion test. For cytotoxicity assay, fibroblast cell viability increased in CS-G/HA-NPs hydrogels compared with CS-G group after 24 hr incubation. Consequently, the potential ability of CS-G/HA-NPs hydrogels as a controlled drug delivery system has been verified.

Unconventional Passive Enhancement of Transdermal Drug Delivery: toward a Mechanistic Understanding of Penetration Enhancers Releasing from Acrylic Pressure-Sensitive Adhesive of Patches.

PURPOSE: Penetration enhancers (PEs) enhancing efficacy depends on two processes: PEs release from patches and action on skin. Compared with their action on skin, PEs release process was poorly understood. Therefore, the purpose of this study was to make a mechanistic understanding of PEs release from acrylic pressure-sensitive adhesive of patches and propose an unconventional enhancement of PEs efficacy. METHODS: PEs efficacy was evaluated both in drug permeation study and drug pharmacokinetic study. Confocal Raman spectroscopy was employed to observe PEs release behavior by mapping PEs dynamic distribution in skin. The mechanism of PEs release behavior was provided from molecular interaction and rheology using FT-IR, molecular docking, molecular dynamic simulation and rheometer, separately. RESULTS: The release behavior of PEs themselves greatly restricted their efficacy. By using PEG 400, an improvement of oleic acid (OA) release behavior was achieved, and the efficacy of OA was significantly enhanced with enhancing ratio (ER) from 2.69 to 4.10 and AUClast from 1574 ± 87 to 2664 ± 249 ng·h/mL, separately. The improvement of OA release behavior was primarily resulted from reduction of the interaction between OA and adhesive, which was caused by other small molecules with a strong ability in forming hydrogen bonds with adhesive. Also, the rigidity of adhesive was a factor in affecting PEs release behavior. CONCLUSIONS: An unconventional passive enhancement of transdermal drug delivery was achieved via improving PEs themselves releasing from acrylic pressure-sensitive adhesive. Graphical abstract Influence of PEs release behavior on drug permeation through skin and molecular mechanism.

Magneto-plasmonic nanostars for image-guided and NIR-triggered drug delivery.

Smart multifunctional nanoparticles with magnetic and plasmonic properties assembled on a single nanoplatform are promising for various biomedical applications. Owing to their expanding imaging and therapeutic capabilities in response to external stimuli, they have been explored for on-demand drug delivery, image-guided drug delivery, and simultaneous diagnostic and therapeutic (i.e. theranostic) applications. In this study, we engineered nanoparticles with unique morphology consisting of a superparamagnetic iron oxide core and star-shaped plasmonic shell with high-aspect-ratio gold branches. Strong magnetic and near-infrared (NIR)-responsive plasmonic properties of the engineered nanostars enabled multimodal quantitative imaging combining advantageous functions of magnetic resonance imaging (MRI), magnetic particle imaging (MPI), photoacoustic imaging (PAI), and image-guided drug delivery with a tunable drug release capacity. The model drug molecules bound to the core-shell nanostars were released upon NIR illumination due to the heat generation from the core-shell nanostars. Moreover, our simulation analysis showed that the specific design of the core-shell nanostars demonstrated a pronounced multipolar plasmon resonance, which has not been observed in previous reports. The multimodal imaging and NIR-triggered drug release capabilities of the proposed nanoplatform verify their potential for precise and controllable drug release with different applications in personalized medicine.

Characterization, Optimization, In Vitro and In Vivo Evaluation of Simvastatin Proliposomes, as a Drug Delivery.

Simvastatin a cholesterol-lowering agent used to treat hypercholesterolemia, coronary heart disease, and dyslipidemia. However, simvastatin (SV) has shown low oral bioavailability in GIT. The main purpose of the work was to develop proliposomal formulations to increase the oral bioavailability of SV. Film deposition on the carrier method has been used to prepare the proliposomes. The proliposomes were assessed for morphology, particulate size, entrapment efficacy, drug-polymer compatibility, in vitro and in vivo studies. FTIR and DSC results revealed no drug-polymer interaction. SEM and XRD analysis conform; proliposomes are spherical, amorphous in nature, so that it enhances the solubility of SV between 15.01 ± 0.026 and 57.80 ± 0.015 µg/mL in pH 7.4 phosphate buffer. The optimised formulation (PL6) shows drug release up to 12 h (99.78 ± 0.067%). The pharmacokinetics of pure SV and SV proliposomes (SVP) in rats were Tmax 2 ± 0.5 and 4 ± 0.7 h, Cmax 10.4 ± 2.921 and 21.18 ± 12.321 µg/mL, AUC0-∞ 67.124 ± 0.23 and 179.75 ± 1.541 µg/mL h, respectively. Optimised SVP shows a significant improvement in the rate and absorption of SV. The optimised formulation showed enhanced oral bioavailability of SV in Albino Wister rats and offers a new technique to improve the poor water-soluble drug absorption in the gastrointestinal system.

Preclinical evaluation of new formulation concepts for abiraterone acetate bioavailability enhancement based on the inhibition of pH-induced precipitation.

Abiraterone acetate is a potent drug used for the treatment of metastatic castration resistant prostate cancer. However, currently marketed product containing crystalline abiraterone acetate exhibits strong positive food effect which results in strict dosing regimen. In the present work, a rational approach towards design of novel abiraterone acetate formulations that would allow increased bioavailability on a fasting stomach and thus decreased food effect is presented. Precipitation experiments in biorelevant media were designed to assess pH induced precipitation of the drug and a pool of polymeric excipients was then screened for their potential to inhibit precipitation. The best performing polymeric excipients were subsequently used as carriers for the preparation of amorphous solid dispersions. Two main approaches were followed in order to formulate the drug. The first approach relies on the suppression of precipitation from a supersaturated solution whereas the second one is based on the hypothesis that when the release of the drug is tuned, optimal uptake of the drug can be reached. Optimized formulation prototypes were tested in a rat animal model in an incomplete block, randomized bioequivalence study to assess their relative bioavailability under fasting conditions. We show that both formulation approaches lead to increased bioavailability of abiraterone acetate on a fasting stomach with bioavailability in rats being enhanced up to 250% compared to the original drug product containing crystalline drug.

Formulation and evaluation of niosomal vesicles containing ondansetron HCL for trans-mucosal nasal drug delivery.

Ondansetron HCl is a (5-HT3) serotonin receptor antagonist, used as anti-emetic drug in combination with anticancer agents. Conventional dosage forms have poor bioavailability and patient compliance. These problems can be reduced by the use of nasal niosomal thermo-reversible in situ gelling system. Niosomes were formulated using various surfactants (Span 60, Span 80, Tween 20, and Tween 80) in different ratios using the thin-film hydration technique. Niosomes were evaluated for particle size, zeta potential, transmission electron microscopy (TEM) imaging, drug entrapment efficiency, and in vitro drug release. Niosomes prepared using Span 60 and cholesterol in the ratio 1:1 (F5) showed higher entrapment efficiency (76.13 ± 1.2%) and in vitro drug release (91.76%) after 12 h was optimized. The optimized niosomes were developed into thermo-reversible in situ gel, composed of Poloxamer 407 and sodium carboxymethyl cellulose, prepared by cold method technique. Compatibility study (FTIR, DSC) was made for drugs and excipients that showed no significant interaction. The gel formulation G5 showed the most suitable gelation temperature (31 °C), viscosity (1250 mpoise), bioadhesion force (5860 ± 28 dyne/cm2), and in vitro drug release (70.6%) after 12 h. Comparative in vivo pharmacokinetic study on rabbits showed a sustained release and higher relative bioavailability of the prepared nasal in situ gel compared to similar dose of oral tablets (202.4%) which make ondansetron HCl niosomal nasal thermo-sensitive in situ gel a more convenient dosage form for the administration of ondansetron HCl than oral tablets.

Cetuximab-conjugated chitosan-pectinate (modified) composite nanoparticles for targeting colon cancer.

In the present study, we successfully developed a cetuximab-conjugated modified citrus pectin-chitosan nanoparticles for targeted delivery of curcumin (Cet-MCPCNPs) for the treatment of colorectal cancer. In vitro analyses revealed that nanoparticles were spherical with size of 249.33 ±â€¯5.15 nm, a decent encapsulation efficiency (68.43 ±â€¯2.4%) and a 'smart' drug release profile. 61.37 ±â€¯0.70% of cetuximab was adsorbed to the surface of the nanoparticles. Cellular uptake studies displayed enhanced internalization of Cet-MCPCNPs in Caco-2 (EGFR +ve) cells, which ultimately resulted in a significant reduction in cancer cell propagation. The cell cycle analysis indicated that Cet- MCPCNPs induced cell death in enhanced percentage of Caco-2 cells by undergoing cell cycle arrest in the G2/M phase. These data suggest that Cet-MCPCNPs represent a new and promising targeting approach for the treatment of colorectal cancer.

Levofloxacin Hemihydrate In Situ Gelling Ophthalmic Solution: Formulation Optimization and In Vitro and In Vivo Evaluation.

Bacterial conjunctivitis is a leading cause of ocular infections requiring short-term therapeutic treatment with frequent administration of drugs on daily basis. Topical dosage forms available in the market for the treatment of bacterial conjunctivitis such as simple drug solutions and suspensions are rapidly eliminated from the precorneal space upon instillation due to tear turn over and nasolacrimal drainage, limiting intraocular bioavailability of drug to less than 10% of the administered dose. To overcome issues related to conventional drop, an effort was made to design and evaluate prolong release ophthalmic solution of levofloxacin hemihydrate (LFH) using ion-sensitive in situ gelling polymer. Gellan gum was used as the in situ gelling agent. Formulations were screened based on in vitro gelation time, in vitro drug release, and stability towards sol to gel conversion upon storage. The prototype formulations exhibiting quick in vitro gelling time (< 15 s), prolonged in vitro drug release (18-24 h), and stability for at least 6 months at 25°C/40% relative humidity (RH) and 40°C/25% RH were evaluated for pharmacokinetic studies using healthy New Zealand white rabbits. Tested formulations were found to be well-tolerated and showed significant increase in AUC0-24 (22,660.39 h ng/mL) and mean residence time (MRT 12 h) as compared with commercially available solution Levotop PF® (Ajanta Pharma Ltd., India)(AUC0-24 6414.63 h ng/mL and MRT 4 h). Thus, solution formulations containing in situ gelling polymer may serve as improved drug delivery system providing superior therapeutic efficacy and better patient compliance for the treatment of bacterial conjunctivitis.

Preparation and Evaluation of Mosapride Citrate Dual-Release Dry Suspension.

In this paper, a novel formulation of dual-release dry suspension of mosapride citrate (DRDS-MC) was designed which can be quickly released in the stomach while having sustained-release effect. Co-grinding mixture of mosapride citrate (MC) together with L-HPC as hydrophilic excipient was prepared in order to improve the solubility of MC. The co-grinding mixture was characterized by solubility studies, DSC, X-RD, SEM, FTIR, and size distribution before the preparation of the DRDS-MC. Then, the co-grinding mixture was used to prepare DRDS-MC via wet granulation method. The evaluation of DRDS-MC was focused on physicochemical properties, intestinal absorption, and pharmacokinetics. The results of DSC, X-RD, SEM, FTIR, and size distribution indicated that MC resides in co-grinding mixture with no crystalline changes, hydrogen bonds made L-HPC greatly improving the solubility of MC. Then, the dissolution of DRDS-MC reached 70% in pH 1.2 within 2 h, and the 12-h dissolution of MC in pH 6.8 was nearly 80%. The sedimentation volume after 3 h was 0.94 and redispersibility was good. The linear regression equation between in vitro release of DRDS-MC and intestinal absorption fraction in rats was: Y = 29.215 + 47.535*X (r = 0.952). At last, pharmacokinetic studies in beagle dogs demonstrated that DRDS-MC has prolonged effect compared with commercial formulation Gasmotin as a reference. All results indicated that the DRDS-MC could be quickly released in the stomach while having sustained-release effect.

Polydopamine-based Implantable Multifunctional Nanocarpet for Highly Efficient Photothermal-chemo Therapy.

We report a design and fabricate multifunctional localized platform for cancer therapy. Multiple stimuli-responsive polydopamine (PDA) was used for surface modification of electrospun doxorubicin hydrochloride (DOX) loaded polycaprolactone (PCL) fibers to make a designated platform. Photothermal properties such as photothermal performance and stability of the resulting composite mats were studied under the irradiation of the near-infrared (NIR) laser of 808 nm. With the incorporation of PDA into the fiber, a remarkable increase of local temperature was recorded under NIR illumination in a concentration-dependent manner with excellent stability. Drug released assay results revealed PDA coated PCL-DOX mats showed pH and NIR dual responsive behavior thereby exhibiting improved drug release in an acidic medium compared to physiological pH condition (pH 7.4) which is further increased by NIR exposure. The cancer activity in vitro of the mats was evaluated using cell counting (CCK) and live and dead cell assays. The combined effect of NIR mediated hyperthermia and chemo release resulting improved cells death has been reported. In summary, this study presents a major step forward towards a therapeutic model to cancer treatment utilizing pH and NIR dual responsive property from PDA alone in a fibrous mat.

Effect of Mild Hyperthermia on Transdermal Absorption of Nicotine from Patches.

Application of heat (hyperthermic conditions) on skin is known to enhance drug transfer and facilitate skin penetration of molecules. The aim of this work was to study the effect of hyperthermia on the drug release and skin permeation from nicotine transdermal patches. The drug release and skin permeation were characterized by in vitro release test and in vitro permeation test. The temperature was maintained at 32 °C as control (simulating normal physiological skin temperature) and 42 °C as hyperthermia condition. The in vitro release test was carried out using USP apparatus 5-Paddle over disk method for a transdermal patch. Skin permeation study was carried out across porcine skin using the flow through cells (PermeGear, Inc.) with an active diffusion area of 0.94 cm2. Mechanistic studies (parameters such as partition coefficient, TEWL and electrical resistivity) were also performed to understand the mechanisms involved in determining the influence of hyperthermia on drug delivery from transdermal patches of nicotine. The rate and extent of drug release from nicotine patch was not significantly different at two temperatures (Cumulative release after 12 h was 43.99 ± 3.29% at 32 °C and 53.70 ± 5.14% at 42 °C). Whereas, in case of in vitro permeation studies, the nicotine transdermal permeation flux for patch was threefold higher at 42 °C (100.1 ± 14.83 µg/cm2/h) than at 32 °C (33.3 ± 14.83 µg/cm2/h). The mechanistic studies revealed that the predominant mechanism of enhancement of drug permeation by hyperthermia condition is by the way of increasing the skin permeability. There is a potential concern of dumping of higher dose of nicotine via transdermal route.

Magnetic double-network hydrogels for tissue hyperthermia and drug release.

Magnetic-field driven soft materials have found extensive applications in fields such as soft robotics, shape morphing and biomedicine. Compared to magnetoactive elastomers (MAEs), magnetic hydrogels have shown significant advantages for in vivo applications, because of their better biocompatibility, as well as their soft and wet nature. However, the poor mechanical properties and ion sensitivity of conventional magnetic hydrogels will severely limit their applications especially under physiological conditions. Double network hydrogels are tough and stable, but do not respond to environmental stimuli. Here magnetic double network (M-DN) hydrogels have been developed with outstanding mechanical performances and ion-resistant stability. M-DN hydrogels show a high modulus of ∼0.4 MPa and a high toughness of ∼1500 J m-2. The volume, magnetic and mechanical properties of M-DN hydrogels show negligible deterioration in ionic solutions. M-DN hydrogels exhibit magnetic responsiveness and have been used for tissue hyperthermia and drug release by magnetic induction heating. The induction heating behavior of M-DN hydrogels can be tuned to meet the clinical requirements, by changing the magnetic field strength or the composition of magnetic hydrogels. M-DN hydrogels may be inspiring to the development of responsive DN hydrogels and expand their more potential applications in load-bearing biomedical engineering.

Bioavailability Enhancement of Aripiprazole Via Silicosan Particles: Preparation, Characterization and In vivo Evaluation.

The aim of this study was to design a novel carrier for enhancing the bioavailability of the poorly water-soluble drug, aripiprazole (ARP). Silicosan, the applied carrier, was obtained by chemical interaction between tetraethyl orthosilicate (TEOS) and chitosan HCl. Different ARP-loaded silicosan particles were successfully prepared in absence and presence of one of the following surfactants; Tween 80, Poloxamer 407 and cetyltrimethylammonium bromide (CTAB). The prepared ARP-loaded silicosan particles were thoroughly investigated for their structures using FTIR, XRD, and DSC analysis as well as their particle size, zeta potential, flowability, drug content, and in vitro drug release efficiencies. The prepared ARP-loaded silicosan particles were characterized by amorphous structure, high drug entrapment efficiency and a remarkable improvement in the release of aripiprazole in simulated gastric fluid. SEM and EDX revealed that the morphology and silica atom content in the prepared ARP-loaded silicosan particles were affected by the used surfactant in their formulations. The selected ARP-loaded silicosan particles were subjected to in vivo study using rabbits. The obtained pharmacokinetic results showed that the relative bioavailability for orally administered ARP-loaded silicosan particles (SC-2-CTAB) was 66% higher relative to the oral suspension (AUC0-10h was 16.38 ± 3.21 and 27.23 ± 2.35 ng.h/mL for drug powder and SC-2-CTAB formulation, respectively). The obtained results suggested the unique-structured silicosan particles to be used as successful vehicle for ARP.

Amisulpride-CD-Loaded Liposomes: Optimization and In Vivo Evaluation.

Amisulpride (AMS) is an atypical antipsychotic agent used for the treatment of schizophrenia. The effect of different variables, i.e., the type of cyclodextrins (CDs), ratio of drug/CDs, and type of loading on the prepared AMS-CD liposomes (single and double loaded) was studied by applying 23 full factorial design. Double-loaded liposomes are loaded with AMS-hydroxyl propyl-ß-cyclodextrin (HP-ß-CD) in the aqueous phase and free drug in the lipophilic bilayer, while single-loaded liposomes are loaded only with AMS-HP-ß-CD in the aqueous phase. Entrapment efficiency, particle size, polydespersibility, and zeta potential were selected as dependent variables. Design Expert® software was used to obtain an optimized formulation with high entrapment efficiency (64.55 ± 1.27%), average particle size of 40.1 ± 2.77 nm, polydespersibility of 0.44 ± 0.37, and zeta potential of - 48.8 ± 0.28. Optimized formula was evaluated for in vitro release, surface morphology and stability study was also conducted. AMS-HP-ß-CD in double-loaded liposomes exhibited higher drug release than those in the conventional liposomes and in the single-loaded liposomes. The maximum plasma concentration (Cmax) of AMS in optimized AMS-HP-ß-CD double-loaded liposomal formulation increased by 1.55- and 1.29-fold, as compared to the commercial tablets and conventional liposomes, respectively. However, the relative bioavailability of AMS double-loaded liposomes was 1.94- and 1.28-folds of commercial tablet and conventional liposomes, respectively.

Nano-engineering of biomedical prednisolone liposomes: evaluation of the cytotoxic effect on human colon carcinoma cell lines.

OBJECTIVES: Liposomes have attracted the attention of researchers due to their potential to act as drug delivery systems for cancer treatment. The present investigation aimed to develop liposomes loaded with prednisolone base and the evaluation of the antiproliferative effect on human colon carcinoma cell lines. METHODS: Liposomes were elaborated by following a reproducible thin film hydration technique. The physicochemical characterization of liposomes included photon correlation spectroscopy, microscopy analysis, Fourier transform infrared spectroscopy, rheological behaviour and electrophoresis. On the basis of these data and drug loading values, the best formulation was selected. Stability and drug release properties were also tested. KEY FINDINGS: Resulting liposomes exhibited optimal physicochemical and stability properties, an excellent haemocompatibility and direct antiproliferative effect on human colon carcinoma T-84 cell lines. CONCLUSIONS: This study shows direct antitumour effect of prednisolone liposomal formulation, which opens the door for liposomal glucocorticoids as novel antitumour agents.

Deep Tumor Penetrating Bioparticulates Inspired Burst Intracellular Drug Release for Precision Chemo-Phototherapy.

The relevance of personalized medicine has inspired research for individually concerted diagnosis and therapy. Numerous efforts are devoted to designing drug particulates with capabilities of tumor penetrating and subcellular trafficking to concurrently discharge theranostics in response to multistimulations. In this study, a bioinspired particulate, formulated with whole components of native high-density lipoproteins (HDLs) and decorated with the tumor-penetrating peptide iRGD, is proposed to promote tumor penetration of HDLs (pHDLs) together with payloads. Specifically, paclitaxel (PTX), and the NIR fluorescent probe indocyanine green (ICG) are integrated into pHDLs (pHDL/PTX-ICG) for synergetic chemo-phototherapy. Inspired by lipoproteins, pHDLs are not only restored from naturally occurring materials but also possessed artificially endowed functions, leading to an enhanced cellular uptake, higher accumulation, and deep penetration into tumors without causing appreciable adverse effects, compared to reconstituted HDLs or lipid-based nanoparticles. After intravenous administration, pHDL/PTX-ICG performs a burst of intracellular drug release and imaging-guided precision chemo-phototherapy upon NIR irradiation that completely eradicates xenograft tumors. Neither recurrence nor significant toxicity is observed due to maneuvered regional photodynamic and photothermal therapy. Taken together, pHDL/PTX-ICG is proven to be a promising platform to achieve deep tumor penetration and imaging-guided chemo-phototherapy.

Topical Delivery of Fenoprofen Calcium via Elastic Nano-vesicular Spanlastics: Optimization Using Experimental Design and In Vivo Evaluation.

The aim of this study was to investigate the potential of surfactant-based nanovesicular system (spanlastics) for topical delivery of fenoprofen calcium (FPCa) to eliminate its oral gastrointestinal adverse effects. FPCa-loaded spanlastics were prepared by thin film hydration (TFH) technique according to a full factorial design to investigate the influence of formulation variables on the drug entrapment efficiency (%EE), particle size (PS), deformability index (DI), and the % drug released after 24 h through the cellulose membrane (Q24h) using Design-Expert® software. The optimized formula (composed of Span 60 and Tween 60 as an edge activator at weight ratio of 8: 2 in presence of Transcutol P as a cosolvent in the hydration media) exhibited the highest %EE (49.91 ± 2.60%), PS of 536.1 ± 17.14 nm, DI of 5.07 ± 0.06 g, and Q24h of 61.11 ± 2.70%; it was also characterized for morphology and physical stability. In vitro release study of FPCa-loaded spanlastic gel and conventional FPCa gel through a synthetic membrane and hairless rat skin were evaluated. The skin permeation study revealed that spanlastic gel exhibited both consistent and prolonged action. Finally, the % inhibition of carrageenan-induced rat paw edema of spanlastic gel was three times higher than the conventional FPCa gel after 24 h. In conclusion, spanlastic-based gel could be a great approach for improving topical delivery of fenoprofen calcium, providing both prolonged and enhanced anti-inflammatory activity in the treatment of arthritis.

NIR Light-Activated Drug Release for Synergetic Chemo-Photothermal Therapy.

Nanocarriers like PEGylated liposomes have achieved enhanced drug accumulation in tumors and reduced systemic side effects, but failed to actively release the carried drug into cancer cells. To obtain improved therapeutic efficacy, we designed a novel liposome that was inserted by the amphiphilic agent PEG-IR780-C13 (PIC-Lipo) and encapsulated therapeutic agent doxorubicin (DOX), termed as DOX@PIC-Lipo. Upon NIR laser irradiation, the novel liposomes could generate hyperthermia and facilitate the release of encapsulated DOX from PIC-Lipo, which were confirmed by photothermal curves and the DOX release assay in vitro, respectively. In addition, the enhanced DOX release and sufficient hyperthermia have performed synergetic therapeutic efficacy both in vitro and in vivo. Therefore, DOX@PIC-Lipo might provide an active strategy to release the loaded drug for synergetic chemo-photothermal combined therapy.

Formulation and evaluation of novel controlled release of topical pluronic lecithin organogel of mefenamic acid.

In the present study, pluronic lecithin based organogels (PLO gels) were formulated as topical carrier for controlled delivery of mefenamic acid. Ten organogel formulations were prepared by a method employing lecithin as lipophilic phase and pluronic F-127 as hydrophilic phase in varying concentrations to study various parameters using in vitro diffusion study and in vivo studies. All formulations were found to be off-white, homogenous, and reluctant to be washed easily and have pH value within the range of 5.56-5.80 which is nonirritant. Polymer concentration increased in formulations of F1 to F5 (lecithin) and F6 to F10 (pluronic) resulted in decrease of the gelation temperature, increase of viscosity and reduction of spreadability of gels having polymer tendency to form rigid 3D network. Organogels with higher viscosity were found to be more stable and retard the drug release from the gel. The formulations of F2 and F3 were selected for kinetic studies and stability studies, as they found to have all physical parameters within acceptable limits, highest percent drug content and exhibited highest drug release in eight hours. The order of drug release from various formulations was found to be F2 > F3 > F10 > F4 > F1 > F9 > F8 > F5 > F7 > F6. The optimized formulation F2 was found to follow zero order rate kinetics showing controlled release of the drug from the formulations. In vivo anti-inflammatory activity of optimized mefenamic acid organogel (F2) against a standard marketed preparation (Volini gel) was found satisfactory and significant.