UPLC-MS/MS Method Development for Simultaneous Estimation of Diclofenac and Resveratrol-Loaded Liposomal Gel Formulation in Mice Skin Model: Application to Dermatokinetic Study.

The current research work describes the development of a simple, fast, sensitive and efficient bioanalytical UPLC/MS-MS method for the simultaneous estimation of diclofenac and resveratrol in mice skin samples. Quetiapine was used as an internal standard (IS). Analytical separation was performed on ACQUITY UPLC C18 Column (2.1 × 100 mm; 1.7 µm) using ammonium acetate (5 mM) in water and methanol (B) with isocratic elution at ratio of (50, 50 v/v) and flow rate of 0.4 mL/min. The duration of separation was maintained for 3 min. Electrospray ionization mass spectrometry in a positive and negative ionization mode was used for detection. Selective ion mode monitoring was used for the quantification of m/z 296.025> 249.93 for diclofenac, m/z 229.09 > 143.03 for resveratrol and MRM/ES+ve mode applied in m/z 384.25> 253.189 for IS transitions from parent to daughter ion. The lower detection and quantification limits were accomplished, and precision (repeatability and intermediate precision) with a coefficient of variation below 10% produced satisfactory results. The developed bioanalytical method was found to be useful for its suitability for the dermatokinetic evaluation of treatments through rat skin. Improvement in AUC (1.58-fold for diclofenac and 1.60-fold for resveratrol) and t1/2 in the dermis (2.13 for diclofenac and 2.21-fold for resveratrol) followed by epidermis was observed for diclofenac and resveratrol-loaded liposomal gel formulation over the conventional gel. Overall, the developed method for the dermatokinetic studies of the above-mentioned dual drugs-loaded liposome gel was found to be reproducible and effective for bioanalytical.

Chiral-engineered supraparticles: Emerging tools for drug delivery.

The handedness of chiral-engineered supraparticles (CE-SPs) influences their interactions with cells and proteins, as evidenced by the increased penetration of breast, cervical, and myeloma cell membranes by d-chirality-coordinated SPs. Quartz crystal dissipation and isothermal titration calorimetry have been used to investigate such chiral-specific interactions. d-SPs are more thermodynamically stable compared with l-SPs in terms of their adhesion. Proteases and other endogenous proteins can be shielded by the opposite chirality of d-SPs, resulting in longer half-lives. Incorporating nanosystems with d-chirality increases uptake by cancer cells and prolongs in vivo stability, demonstrating the importance of chirality in biomaterials. Thus, as we discuss here, chiral nanosystems could enhance drug delivery systems, tumor markers, and biosensors, among other biomaterial-based technologies, by allowing for better control over their features.

Crafting ɣ-L-Glutamyl-l-Cysteine layered Human Serum Albumin-nanoconstructs for brain targeted delivery of ropinirole to attenuate cerebral ischemia/reperfusion injury via "3A approach".

Treatment of Ischemic Stroke is inordinately challenging due to its complex aetiology and constraints in shuttling therapeutics across blood-brain barrier. Ropinirole hydrochloride (Rp), a propitious neuroprotectant with anti-oxidant, anti-inflammatory, and anti-apoptotic properties (3A) is repurposed for remedying ischemic stroke and reperfusion (I/R) injury. The drug's low bioavailability in brain however, limits its therapeutic efficacy. The current research work has reported sub-100 nm gamma-L-Glutamyl-L-Cysteine coated Human Serum Albumin nanoparticles encapsulating Rp (C-Rp-NPs) for active targeting in ischemic brain to encourage in situ activity and reduce unwanted toxicities. Confocal microscopy and brain distribution studies confirmed the enhanced targeting potentiality of optimized C-Rp-NPs. The pharmacokinetics elucidated that C-Rp-NPs could extend Rp retention in systemic circulation and escalate bioavailability compared with free Rp solution (Rp-S). Additionally, therapeutic assessment in transient middle cerebral occlusion (tMCAO) model suggested that C-Rp-NPs attenuated the progression of I/R injury with boosted therapeutic index at 1000 times less concentration compared to Rp-S via reinstating neurological and behavioral deficits, while reducing ischemic neuronal damage. Moreover, C-Rp-NPs blocked mitochondrial permeability transition pore (mtPTP), disrupted apoptotic mechanisms, curbed oxidative stress and neuroinflammation, and elevated dopamine levels post tMCAO. Thus, our work throws light on fabrication of rationally designed C-Rp-NPs with enormous clinical potential.

Nanostructured Lipid Carrier-Based Codelivery of Raloxifene and Naringin: Formulation, Optimization, In Vitro, Ex Vivo, In Vivo Assessment, and Acute Toxicity Studies.

This work aimed to develop dual drug-loaded nanostructured lipid carriers of raloxifene and naringin (RLX/NRG NLCs) for breast cancer. RLX/NRG NLCs were prepared using Compritol 888 ATO and oleic acid using a hot homogenization-sonication method and optimized using central composite design (CCD). The optimized RLX/NRG NLCs were characterized and evaluated using multiple technological means. The optimized RLX/NRG NLCs exhibited a particle size of 137.12 nm, polydispersity index (PDI) of 0.266, zeta potential (ZP) of 25.9 mV, and entrapment efficiency (EE) of 91.05% (raloxifene) and 85.07% (naringin), respectively. In vitro release (81 ± 2.2% from RLX/NRG NLCs and 31 ± 1.9% from the RLX/NRG suspension for RLX and 93 ± 1.5% from RLX/NRG NLCs and 38 ± 2.01% from the RLX/NRG suspension for NRG within 24 h). Concurrently, an ex vivo permeation study exhibited nearly 2.3 and 2.1-fold improvement in the permeability profiles of RLX and NRG from RLX/NRG NLCs vis-à-vis the RLX/NRG suspension. The depth of permeation was proved with CLSM images which revealed significant permeation of the drug from the RLX/NRG NLCs formulation, 3.5-fold across the intestine, as compared with the RLX/NRG suspension. An in vitro DPPH antioxidant study displayed a better antioxidant potential of RLX/NRG in comparison to RLX and NRG alone due to the synergistic antioxidant effect of RLX and NRG. An acute toxicity study in Wistar rats showed the safety profile of the prepared nanoformulations and their excipients. Our findings shed new light on how poorly soluble and poorly permeable medicines can be codelivered using NLCs in an oral nanoformulation to improve their medicinal performance.

Development of a Validated UPLC-MS/MS Method for Simultaneous Estimation of Neratinib and Curcumin in Human Plasma: Application to Greenness Assessment and Routine Quantification.

A validated ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the first-ever simultaneous analysis of neratinib, curcumin and internal standard (imatinib) using acetonitrile as the liquid-liquid extraction medium. On a BEH C18 (100 mm × 2.1 mm, 1.7 µm) column, the analytes were separated isocratically using acetonitrile (0.1% formic acid):0.002M ammonium acetate. The flow rate was set at 0.5 mL.min-1. The authors utilized multiple reaction monitoring-based transitions for the precursor-to-product ion with m/z 557.099 â†’ 111.928 for neratinib, m/z 369.231 â†’ 176.969 curcumin and m/z 494.526 â†’ 394.141 for imatinib during the study. Validation of the method as per United States Food and Drug Administration requirements for linearity (5-40 ng mL-1), accuracy and precision, stability, matrix effect, etc. were investigated and were observed to be acceptable. Afterward, we evaluated the method for establishing its greenness profile by using two greenness assessment tools and found it green. Overall, a reliable green UPLC-MS/MS method was devised and used to estimate neratinib and curcumin in human plasma simultaneously.

Wearable smart devices in cancer diagnosis and remote clinical trial monitoring: Transforming the healthcare applications.

During the past two decades, the era of digitalization in pharmaceutical device manufacturing has gained significant momentum for maintaining human health. From various available technologies, internet of things (IoT) sensors are being increasingly used as wearable devices (e.g., smart watches, wrist bands, mobile phones, tablets, implantable pumps, etc.) that enable real-time monitoring of data. Such devices are integrated with smart materials that typically monitor the real-time data (blood pressure, blood sugar, heart and pulse rate, cytokine levels, etc.) to advise patients and physicians. Hence, there has been a great demand for wearable devices as potential tools for remote clinical trial monitoring in cancers and other diseases and they are proving to be very cost-effective.

Systematic Development of Solid Lipid Nanoparticles of Abiraterone Acetate with Improved Oral Bioavailability and Anticancer Activity for Prostate Carcinoma Treatment.

In the present work, an attempt was undertaken to improve the oral bioavailability and anticancer activity of abiraterone acetate. Solid lipid nanoparticles (SLNs) were developed using the quality by design (QbD) principles and evaluated through in vitro, ex vivo, and in vivo studies. Solid lipid suitability was evaluated by equilibrium solubility study, while surfactant and cosurfactant were screened based on the ability to form microemulsion with the selected lipid. SLNs were prepared by emulsion/solvent evaporation method using glyceryl monostearate, Tween 80, and Poloxamer 407 as the solid lipid, surfactant, and cosurfactant, respectively. Box-Behnken design was applied for optimization of material attributes and evaluating their impact on particle size, polydispersity index, zeta potential, and entrapment efficiency of the SLNs. In vitro drug release study was evaluated in simulated gastric and intestinal fluids. Cell culture studies on PC-3 cells were performed to evaluate the cytotoxicity of the drug-loaded SLNs in comparison to the free drug suspension. Qualitative uptake was evaluated for Rhodamine B-loaded SLNs and compared with free dye solution. Ex vivo permeability was evaluated on Wistar rat intestine and in vivo pharmacokinetic evaluation on Wistar rats for SLNs and free drug suspension. Concisely, the SLNs showed potential for significant improvement in the biopharmaceutical performance of the selected drug candidate over the existing formulations of abiraterone acetate.

Active pharmaceutical ingredients (APIs) in ionic liquids: An effective approach for API physiochemical parameter optimization.

Ionic liquids (ILs) are widely used as solvents, co-solvents and permeation enhancers in the biomedical and pharmaceutical fields. There are many advantages to using active pharmaceutical ingredients (APIs) in the production of ILs for drug delivery, including the ability to tailor solubility, improve thermal stability, increase dissolution, regulate drug release, improve API permeability, and modulate cytotoxicity on tumor cells. Such an approach has shown significant potential as a tool for drug delivery. As a result, APIs converted into ILs are used as active components in solutions, emulsions, and even nanoparticles (NPs). In this review, we explore the use and physiochemical characteristics of APIs via ILs, including improvements of their physicochemical properties in preformulation and formulation development.

Recent Advances in Nanotechnology-Based Targeted Therapeutics for Breast Cancer Management.

Despite the great efforts that have been achieved in breast cancer treatment, it remains a significant cause of death in women and is a serious health problem. Treatment with chemotherapy drugs faces various challenges, such as toxicity and chemoresistance to chemotherapeutic drugs, which hinder their therapeutic success and clinical experiments. This review focuses on targeting nanocarrier approaches to target chemotherapy drugs to receptor targets that are overexpressed on the surface of breast cancer cells. In particular, the most commonly targeted nanocarriers for the chemotherapeutic agents examined by the different researcher groups, such as liposomes, dendrimers, polymeric micelles, lipid particulates, polymeric nanoparticles, and carbon nanotubes, have been reviewed. Moreover, we summarized the molecular receptors or targets that are the most commonly overexpressed in breast cancer cells and the natural and synthetic ligands studied for use as targeting moieties to functionalize chemotherapeutically loaded nanocarriers for potential specific breast cancer targeting.

Chemometrics-assisted development of a validated LC method for simultaneous estimation of temozolomide and γ-linolenic acid: Greenness assessment and application to lipidic nanoparticles.

The described work entails the development of a simple, sensitive, green, and robust high-performance liquid chromatographic (HPLC) method for simultaneous estimation of temozolomide (TMZ) and γ-linolenic acid (GLA). The chemometric factor screening study helped identify the critical method parameters optimized using Box-Behnken design for improved understanding and enhancing the method performance. Chromatographic separation was performed on a Kinetex® C18 column (150 × 4.6 mm, 5 µm particle size) using methanol: water (pH adjusted to 3.5 using 0.5% v/v O-phosphoric acid) as the mobile phase at 0.5 mL/min flow rate and diode array detection between 210 and 360 nm. The linearity of the method was observed for concentrations of TMZ and GLA ranging between 1 and 100 µg.mL-1 (R2 = 0.999, p < 0.05). Accuracy evaluation showed good percent recovery within 97.9-100%, while intra- and inter-day precision showed RSD values within 0.37%-1.01%. The limit of detection and quantification for TMZ was found to be 0.75 and 1.0 µg.mL-1, respectively, while the values 0.55 and 1.0 µg.mL-1, respectively, were observed for GLA. System suitability (96.9-102.8%), its limits, and robustness evaluation indicated good percent recovery within, while RSD values were found to be within the acceptable limit of less than 2%. The method was specific for its ability to detect the analytes and their degradation products during forced degradation studies, which also indicated that TMZ was highly prone to alkaline conditions while GLA showed mild degradation in all the studied conditions. The estimation of both the analytes from lipid nanoparticles formulation showed good values for total drug content (82.6-85.3%), entrapment efficiency (95.4 to 98.7%), and drug loading (25.2 to 38.4%). Overall, the results indicated that the developed method was reliable for its accuracy, precision, sensitivity, and specificity for simultaneous estimation of the analytes. The method was found to be stability-indicating in nature and suitable for simultaneous estimation of TMZ and GLA from the developed nanoparticles formulation. Further, employing a greenness assessment approach established the method greenness.

Hispolon-Loaded Liquid Crystalline Nanoparticles: Development, Stability, In Vitro Delivery Profile, and Assessment of Hepatoprotective Activity in Hepatocellular Carcinoma.

The present work describes the development and characterization of liquid crystalline nanoparticles of hispolon (HP-LCNPs) for treating hepatocellular carcinoma. HP-LCNPs were prepared by a top-down method utilizing GMO as the lipid and Pluronic F-127 as the polymeric stabilizer. The prepared formulations (HP1-HP8) were tested for long-term stability, where HP5 showed good stability with a particle size of 172.5 ± 0.3 nm, a polydispersity index (PDI) of 0.38 ± 0.31 nm, a zeta potential of -10.12 mV ± 0.05, an entrapment efficiency of 86.81 ± 2.5%, and a drug loading capacity of 12.51 ± 1.12%. Optical photomicrography and transmission electron microscopy images demonstrated a consistent, low degree of aggregation and a spherical shape of LCNPs. The effect of temperature and pH on the optimized formulation (HP5) indicated good stability at 45 °C and at pH between 2 and 5. In vitro gastrointestinal stability indicated no significant change in the particle size, PDI, and entrapment efficiency of the drug. The drug release study exhibited a biphasic pattern in simulated gastric fluid (pH 1.2) for 2 h and simulated intestinal fluid (pH 7.4) for up to 24 h, while the best fitting of the profile was observed with the Higuchi model, indicating the Fickian diffusion mechanism. The in vivo pharmacokinetic study demonstrated nearly 4.8-fold higher bioavailability from HP5 (AUC: 1774.3 ± 0.41 µg* h/mL) than from the HP suspension (AUC: 369.11 ± 0.11 µg* h/mL). The anticancer activity evaluation revealed a significant improvement in antioxidant parameters and serum hepatic biomarkers (SGOT, SGPT, ALP, total bilirubin, and GGT) in the diethyl nitrosamine-treated group of rats with the optimized LCNP formulation (HP5) vis-à-vis HP suspension.

Therapeutic Application of Microsponges-based Drug Delivery Systems.

Microsponges delivery systems (MDS) are highly porous, cross-linked polymeric systems that activate due to temperature, pH, or when rubbed. MDS offer a wide range of advantages, like controlled drug release, site-specific action, stability over a broad range of pH, less irritation, cost-effectiveness, and improved patient compliance. They can be transformed into various dosage forms like creams, gels, and lotions. MDS are suitable for the treatment of topical disorders like acne, psoriasis, dandruff, eczema, scleroderma, hair loss, skin cancer, and other dreadful diseases. The applications of MDS in drug delivery are not limited to topical drug delivery but are also explored for oral, parenteral, and pulmonary drug deliveries. Microsponges have been studied for colon targeting of drugs and genes. Additionally, MDS have several applications such as sunscreen, cosmetics, and over-the-counter (OTC) products. Furthermore, MDS do not actuate any irritation, genotoxicity, immunogenicity, or cytotoxicity. Therefore, this review extensively highlights microsponges, their advantages, key factors affecting their characteristics, their therapeutic applications in topical disorders and in cancer, their use as cosmetics, as well as recent advances in MDS and the associated challenges.

Development and Validation of Chemometrics-Assisted Green UPLC-MS/MS Bioanalytical Method for Simultaneous Estimation of Capecitabine and Lapatinib in Rat Plasma.

A chemometrics-oriented green ultra-performance liquid chromatography-mass spectrometry/mass spectrometry method was developed and validated for the first-time simultaneous estimation of capecitabine (CAP) and lapatinib (LPB) along with imatinib (as internal standard (IS)) in rat plasma. Analytes were extracted using ethyl acetate as the liquid-liquid extraction media. In the pre-development phase, principles of analytical eco-scale were used to confirm method greenness. Subsequently, vital method variables, influencing method robustness and performance, were optimized using a chemometrics-based quality-by-design approach. Chromatography was achieved on a BEH C18 (100 × 2.1 mm, 1.7 µm) using isocratic flow (0.5 mL.min-1) of mobile phase acetonitrile (0.1% formic acid):0.002 M ammonium acetate in water as the mobile phase. The mass spectrometric detections were carried out in multiple reaction monitoring modes with precursor-to-product ion transitions with m/z 360.037 → 244.076 for CAP, m/z 581.431 → 365.047 LPB and m/z 494.526 → 394.141 for IS. The bioanalytical method validation studies were performed, ensuring regulatory compliance. Linearity (r2> 0.99) over analyte concentrations ranging from 5 and 40 ng.mL-1 was observed, while acceptable values were obtained for all other validation parameters. In a nutshell, a robust and green bioanalytical method was developed and applied for the simultaneous estimation of two anticancer agents from rat plasma.

A Validated, Rapid and Cost-Efficient HPTLC Method for Quantification of Gamma-Linolenic Acid in Borage Oil and Evaluation of Antioxidant Activity.

Borage oil that is extracted from (Borago officinalis Linn.) is a well-known medicinal plant having various medicinal benefits. In this work, an affordable, simple, reliable, rapid and easily accessible high-performance thin-layer chromatography (HPTLC) method was developed for the estimation of gamma-linolenic acid (GLA) in borage oil. HPTLC method employs thin-layer chromatography (TLC) aluminum plates precoated with silica gel (G60F254) as the stationary phase, and the mixture of hexane:toulene:glacial acetic acid (3:7:1, v/v/v) was used as the mobile phase. Densitometric analysis of the TLC plates was carried out at 200 nm. The developed method showed well-resolved spots with retention factor (Rf) value of 0.53 ± 0.04 for GLA. Various experimental conditions like saturation time for chamber, solvent phase migration and width of the band were studied intensely for selecting the optimum conditions. The method validation was performed for parameters like linearity, accuracy, specificity and precision. The values of limit of detection and limit of quantification for GLA were found to be 0.221 and 0.737 µg/band, respectively. In nutshell, the developed HPTLC method was found to be highly sensitive for the estimation of GLA in the herbal oil samples and formulations.

Development of a Validated Bioanalytical UPLC-MS/MS Method for Quantification of Neratinib: A Recent Application to Pharmacokinetic Studies in Rat Plasma.

Neratinib, a tyrosine kinase inhibitor, was very recently approved by USFDA in 2017 as an anticancer drug to treat of HER2 positive breast cancers. The present work provides an account on the development of a validated bioanalytical UPLC-MS/MS method for quantification of neratinib and internal standard (imatinib) in rat plasma and tissue homogenates. A UPLC having a 100 mm C18 column (1.7 µm sized particles) was used with acetonitrile (0.1% formic acid): 2 mMol of ammonium acetate in water (pH 3.5) as the mobile phase. An efficient chromatographic separation was performed and detection was achieved by monitoring precursor-to-product ion transitions with m/z 557.29 â†’ 112.06 for neratinib and m/z 494.43 â†’ 294.17 for IS. The method demonstrated excellent linearity in the spiked plasma drug concentrating ranging between 1 and 800 ng.mL-1 (r2 = 0999), with lower limit of quantification (LLOQ) was observed at 1 ng.mL-1. Intra-assay and inter-assay precision relative standard deviations were found to be within 6.58. Mean extraction recovery for neratinib and IS were 99.44 and 99.33%, while matrix effect for neratinib and IS was ranging between -4.35 and - 3.66%, respectively. Overall, the method showed successful applicability in pharmacokinetic analysis of pure various formulations in Wistar rat plasma.

EGF-functionalized lipid-polymer hybrid nanoparticles of 5-fluorouracil and sulforaphane with enhanced bioavailability and anticancer activity against colon carcinoma.

The present research work describes development of dual drug-loaded lipid-polymer hybrid nanoparticles (LPHNPs) of anticancer therapeutics for the management of colon cancer. The epidermal growth factor (EGF)-functionalized LPHNPs coloaded with 5-fluorouracil (FU) and sulforaphane (SFN) were prepared by one-step nanoprecipitation method. Box-Behnken design was applied for optimizing the material attributes and process parameters. The optimized LPHNPs revealed particle size 198 nm, polydispersity index 0.3, zeta potential -25.3 mV, and drug loading efficiency 19-20.3% for 5-FU and SFN, respectively. EGF functionalization on LPHNPs was confirmed from positive magnitude of zeta potential to 21.3 mV as compared with the plain LPHNPs. In vitro drug release performance indicated sustained and non-Fickian mechanism release nature of the drugs from LPHNPs. Anticancer activity evaluation in HCT-15 colon cancer cells showed significant reduction (p < 0.001) in the cell growth and cytotoxicity of the investigated drugs from various treatments in the order: EGF-functionalized LPHNPs > plain LPHNPs > free drug suspensions. Overall, the research work corroborated improved treatment efficacy of EGF-functionalized LPHNPs for delivering chemotherapeutic agents for the management of colon carcinoma.

Recent advances in lipid-engineered multifunctional nanophytomedicines for cancer targeting.

Cancer is a leading cause of death in many countries around the world. However, the efficacy of current treatments available for variety of cancers is considered to be suboptimal due to the pathophysiological challenges associated with the disease which limits the efficacy of the anticancer drugs. Moreover, the vulnerability towards off-target effects and high toxicity also limits the use of drugs for the treatment of cancers. Besides, the biopharmaceutical challenges like poor water solubility and permeability of the drugs, along with the absence of active targeting capability further decreases the utility of drugs in cancer therapy. As a result of these deficiencies, the current therapeutic strategies face noncompliance to patients for providing meaningful benefits after administration. With the advancements in nanotechnology, there has been a paradigm shift in the modalities for cancer treatment with the help of phytomedicine-based nanosized drug delivery systems coupled with variegated surface-engineering strategies for targeted drug delivery. Among these delivery systems, lipid-based nanoparticles are considered as one of the highly biocompatible, efficient and effective systems extensively explored for anticancer drug delivery. These include diverse range of systems including liposomes, nanoemulsions, solid lipid nanoparticles, nanostructured lipidic carriers and supramolecular carriers, which alters pharmacokinetic and biodistribution of the drugs for active targeting to the desired site of action by overcoming the biopharmaceutical challenges associated with anticancer drug delivery. The present review endeavours to provide a comprehensive account on the recent advances in the application of lipid-based nanostructured systems for improving the pharmacotherapeutic performance of phytomedicines for cancer targeting application.

Crotamiton-loaded tea tree oil containing phospholipid-based microemulsion hydrogel for scabies treatment: in vitro, in vivo evaluation, and dermatokinetic studies.

Crotamiton (CRT) is a commonly approved drug prescribed for the scabies treatment in many countries across the globe. However, poor aqueous solubility and low bioavailability, and side effects restrict its use. To avoid such issues, an appropriate carrier system is necessary which can address the aforementioned challenges for attaining enhanced biopharmaceutical attributes. The current study intends to provide a detailed account on the development and evaluation of CRT-loaded microemulsion (ME) hydrogel formulation containing tea tree oil (TTO) for improved drug delivery for scabies treatment in a safe and effective manner. Pseudo-ternary phase diagrams were constructed with TTO as the oily phase, and Cremophor®EL was used as the surfactant in a mass ratio 2:1 with co-surfactants (mixture of phospholipid 90G and Transcutol®P), and aqueous solution as the external phase. The optimized drug-loaded ME formulation was evaluated for skin penetration, retention, compliance, and dermatokinetics. The nonirritant behavior of the formulation was revealed by skin histopathology, which showed no changes in normal skin histology. In comparison to the conventional product, dermatokinetic experiments revealed that CRT has greater penetration and distribution in the epidermis of the mice skin. The findings imply that the proposed lipid-based ME hydrogel can aid in the resolution of CRT issues by providing a better and safer delivery option to epidermis and deeper epidermis in substantial quantities.

Nano lipidic carriers for codelivery of sorafenib and ganoderic acid for enhanced synergistic antitumor efficacy against hepatocellular carcinoma.

The current study focuses on the development and evaluation of nano lipidic carriers (NLCs) for codelivery of sorafenib (SRF) and ganoderic acid (GA) therapy in order to treat hepatocellular carcinoma (HCC). The dual drug-loaded NLCs were prepared by hot microemulsion technique, where SRF and GA as the drugs, Precirol ATO5, Capmul PG8 as the lipids, while Solutol HS15 and ethanol was used as surfactant and cosolvents. The optimized drug-loaded NLCs were extensively characterized through in vitro and in vivo studies. The optimized formulation had particle size 29.28 nm, entrapment efficiency 93.1%, and loading capacity 14.21%. In vitro drug release studies revealed>64% of the drug was released in the first 6 h. The enzymatic stability analysis revealed stable nature of NLCs in various gastric pH, while accelerated stability analysis at 25◦C/60% RH indicated the insignificant effect of studied condition on particle size, entrapment efficiency, and loading capacity of NLCs. The cytotoxicity performed on HepG2 cells indicated higher cytotoxicity of SRF and GA-loaded NLCs as compared to the free drugs (p < 0.05). Furthermore, the optimized formulation suppressed the development of hepatic nodules in the Wistar rats and significantly reduced the levels of hepatic enzymes and nonhepatic elements against DEN intoxication. The SRF and GA-loaded NLCs also showed a significant effect in suppressing the tumor growth and inflammatory cytokines in the experimental study. Further, histopathology study of rats treated SRF and GA-loaded NLCs and DEN showed absence of necrosis, apoptosis, and disorganized hepatic parenchyma, etc. over other treated groups of rats. Overall, the dual drug-loaded NLCs outperformed over the plain drugs in terms of chemoprotection, implying superior therapeutic action and most significantly eliminating the hepatic toxicity induced by DEN in Wistar rat model.