Effect of pH and Gastrointestinal Enzymes on Stability of Psoralen, Bakuchicin and Bakuchiol using Simultaneous TLC Densitometric Method and Standardization of commercial formulations containing Psoralea cordyfollia Linn.

Psoralea corylifolia is used for treatmet of skin diseases such as psoriasis, vitiligo. Psoralen is responsible for its effectiveness against psoriasis. Bakuchicin and Bakuchiol are DNA polymerase and topoisomerase II inhibitors. To study the effect of pH and gastrointestinal (GI) enzymes on Psoralen, Bakuchicin and Bakuchiol from Psoralea corylifolia Linn using a simple, sensitive, accurate and robust high performance thin layer chromatographic (HPTLC) method. The method was performed on silica gel 60 F254with n- Hexane : Ethyl acetate ( 7.5 : 2.5 v/v)  as the mobile phase. Densitometric scanning at 285 nm for Psoralen, Bakuchicin and Bakuchiol was used. The method was validated as per the guidelines of International Conference on Harmonization (ICH). In addition the applicability of the method was tested for the standardization of both mono and polyherbal formulations containing the above markers. The Rf values of 0.37, 0.48 and 0.63 were obtained for Psoralen, Bakuchicin and Bakuchiol respectively. The linearity range of 20-120 ng spot-1,  20-120 ng spot-1 and 80-280 ng spot-1  with good correlation coefficients of r2 = 0.998, 0.998 and 0.999 were obtained for Psoralen, Bakuchicin and Bakuchiol  respectively. The method was applied for the in vitro stability studies of above markers in simulated gastric and intestinal fluids to study the effect of pH and GI enzymes. Psoralen was found to be most stable in the simulated physiological fluids whereas other two compounds showed instability. The method was found to be precise, robust and suitable for the routine quality control analysis of plant extracts and polyherbal formulations. Keywords: Psoralea corylifolia Linn, Leguminoceae, HPTLC, Enzymatic stabilit

Solvent Free Twin Screw Processed Silybin Nanophytophospholipid: In Silico, In Vitro and In Vivo Insights

Silybin (SIL) is a polyphenolic phytoconstituent that is commonly used to treat liver disorders. It is difficult to fabricate an orally delivered SIL product due to its low oral bioavailability (0.95%). Therefore, the current research focusses on the development of a novel composition of a phospholipid complex, termed as nanophytophospholipid, of SIL by employing a unique, solvent-free Twin Screw Process (TSP), with the goal of augmenting the solubility and bioavailability of SIL. The optimised SIL-nanophytophospholipid (H6-SNP) was subjected to physicochemical interactions by spectrometry, thermal, X-ray and electron microscopy. The mechanism of drug and phospholipid interaction was confirmed by molecular docking and dynamics studies. Saturation solubility, in vitro dissolution, ex vivo permeation and preclinical pharmacokinetic studies were also conducted. H6-SNP showed good complexation efficiency, with a high practical yield (80%). The low particle size (334.7 ± 3.0 nm) and positively charged zeta potential (30.21 ± 0.3 mV) indicated the immediate dispersive nature of H6-SNP into nanometric dimensions, with good physical stability. Further high solubility and high drug release from the H6-SNP was also observed. The superiority of the H6-SNP was demonstrated in the ex vivo and preclinical pharmacokinetic studies, displaying enhanced apparent permeability (2.45-fold) and enhanced bioavailability (1.28-fold). Overall, these findings indicate that not only can phospholipid complexes be formed using solvent-free TSP, but also that nanophytophospholipids can be formed by using a specific quantity of lipid, drug, surfactant, superdisintegrant and diluent. This amalgamation of technology and unique composition can improve the oral bioavailability of poorly soluble and permeable phytoconstituents or drugs

Mannosylated-Chitosan-Coated Andrographolide Nanoliposomes for the Treatment of Hepatitis: In Vitro and In Vivo Evaluations

A key diterpene lactone of Andrographis paniculata, i.e., andrographolide (AG), exhibits a variety of physiological properties, including hepatoprotection. The limited solubility, short half-life, and poor bioavailability limits the pharmacotherapeutic potential of AG. Therefore, in this study we aimed to formulate and optimize AG-loaded nanoliposomes (AGL) using the Design of Experiment (DOE) approach and further modify the surface of the liposomes with mannosylated chitosan to enhance its oral bioavailability. Physical, morphological, and solid-state characterization was performed to confirm the formation of AGL and Mannosylated chitosan-coated AGL (MCS-AGL). Molecular docking studies were conducted to understand the ligand (MCS) protein (1EGG) type of interaction. Further, in vitro release, ex vivo drug permeation, and in vivo pharmacokinetics studies were conducted. The morphological studies confirmed that AGL was spherical and a layer of MCS coating was observed on their surface, forming the MCS-AGL. Further increase in the particle size and change in the zeta potential of MCS-AGL confirms the coating on the surface of AGL (375.3 nm, 29.80 mV). The in vitro drug release data reflected a sustained drug release profile from MCS-AGL in the phosphate buffer (pH 7.4) with 89.9 ± 2.13% drug release in 8 h. Ex vivo permeation studies showed higher permeation of AG from MCS-AGL (1.78-fold) compared to plain AG and AGL (1.37-fold), indicating improved permeability profiles of MCS-AGL. In vivo pharmacokinetic studies inferred that MCS-AGL had a 1.56-fold enhancement in AUC values compared to plain AG, confirming that MCS-AGL improved the bioavailability of AG. Additionally, the 2.25-fold enhancement in the MRT proves that MCS coating also enhances the in vivo stability and retention of AG (stealth effect). MCS as a polymer therefore has a considerable potential for improving the intestinal permeability and bioavailability of poorly soluble and permeable drugs or phytoconstituents when coated over nanocarriers

Topical Micro-Emulsion of 5-Fluorouracil by a Twin Screw Processor-Based Novel Continuous Manufacturing Process for the Treatment of Skin Cancer: Preparation and In Vitro and In Vivo Evaluations

5-Fluorouracil (5-FU), a BCS class III drug, has low oral bioavailability and is cytotoxic in nature causing severe systemic side effects when administered through the intravenous route. Topical drug delivery could potentially mitigate the systemic side-effects. Microemulsions (MEs) would be an apt solution due to enhanced partitioning of the drug to the skin. However, conventional methods for preparing MEs are inefficient since they are not continuous and are very tedious and time-consuming processes hence revealing the need for the development of continuous manufacturing technology. In our study, 5-FU MEs were prepared using a continuous manufacturing Twin Screw Process (TSP) and its efficiency in the treatment of skin cancer was evaluated. Water-in-oil MEs were prepared using isopropyl myristate as the oil phase and Aerosol OT and Tween 80 as the surfactants. The average particle size was observed to be 178 nm. Transmission electron microscopy was employed to confirm the size and shape of the MEs. FTIR study proved no physical or chemical interaction between the excipients and the drug. In vitro drug release using vertical diffusion cells and ex vivo skin permeation studies showed that the drug was released sustainably and permeated across the skin, respectively. In in vitro cytotoxicity studies, 5-FU MEs were accessed in HaCat and A431 cell lines to determine percentage cell viability and IC50. Skin irritation and histopathological examination implied that the 5-FU MEs did not cause any significant irritation to the skin. In vivo pharmacodynamics studies in rats suggested that the optimised formulation was effective in treating squamous cell carcinoma (SCC). Therefore, 5-FU MEs efficiently overcame the various drawbacks faced during oral and intravenous drug delivery. Also, TSP proved to be a technique that overcomes the various problems associated with the conventional methods of preparing MEs

Hyaluronic Acid-Protein Conjugate Modified Iron-Based MOFs (MIL-101 (Fe)) for Efficient Therapy of Neuroblastoma: Molecular Simulation, Stability and Toxicity Studies

Iron-based metal-organic frameworks (MIL (101)) have recently gained attention in materials science for biomedical applications. In the present work, Iron-based MOF (MIL-101(Fe)) were coated with lactoferrin (Lf) conjugated with hyaluronic acid (HA) and investigated its potential for delivering 5-fluorouracil (5-FU), along with assessing the toxicity profile. The synthesised nanoparticles were extensively characterised using spectroscopic, X-Ray, thermal and electron microscopic techniques. 5-FU was loaded into MOFs, and the drug-loading efficiency and drug release pattern were studied, along with stability testing in pH and serum protein. The toxicity of MIL-101(Fe) was assessed using both in vitro and in vivo techniques such as the haemolysis assay, cell viability assay and acute and subacute toxicity studies in animals. In silico molecular simulation was done to assess the Lf and Tf interaction. The molecular interaction of Lf with Transferrin (Tf) showed strong molecular interaction and negligible fluctuation in the RMSD (root mean square deviation) values. The MOFs were stable and demonstrated sustained drug release patterns. The in vitro cell studies demonstrated biocompatibility and enhanced cellular internalisation of MOFs. The in vivo toxicity studies supported the in vitro results. The synthesised MOFs demonstrated potential as a targeted delivery platform for cancer targeting

Black Phosphorus as Multifaceted Advanced Material Nanoplatforms for Potential Biomedical Applications

Black phosphorus is one of the emerging members of two-dimensional (2D) materials which has recently entered the biomedical field. Its anisotropic properties and infrared bandgap have enabled researchers to discover its applicability in several fields including optoelectronics, 3D printing, bioimaging, and others. Characterization techniques such as Raman spectroscopy have revealed the structural information of Black phosphorus (BP) along with its fundamental properties, such as the behavior of its photons and electrons. The present review provides an overview of synthetic approaches and properties of BP, in addition to a detailed discussion about various types of surface modifications available for overcoming the stability-related drawbacks and for imparting targeting ability to synthesized nanoplatforms. The review further gives an overview of multiple characterization techniques such as spectroscopic, thermal, optical, and electron microscopic techniques for providing an insight into its fundamental properties. These characterization techniques are not only important for the analysis of the synthesized BP but also play a vital role in assessing the doping as well as the structural integrity of BP-based nanocomposites. The potential role of BP and BP-based nanocomposites for biomedical applications specifically, in the fields of drug delivery, 3D printing, and wound dressing, have been discussed in detail to provide an insight into the multifunctional role of BP-based nanoplatforms for the management of various diseases, including cancer therapy. The review further sheds light on the role of BP-based 2D platforms such as BP nanosheets along with BP-based 0D platforms—i.e., BP quantum dots in the field of therapy and bioimaging of cancer using techniques such as photoacoustic imaging and fluorescence imaging. Although the review inculcates the multimodal therapeutic as well as imaging role of BP, there is still research going on in this field which will help in the development of BP-based theranostic platforms not only for cancer therapy, but various other diseases

Nanoparticle drug delivery systems in hepatocellular carcinoma: A focus on targeting strategies and therapeutic applications

Hepatocellular carcinoma (HCC) is recognized as a global health issue accounting for millions of deaths every year. Surgery, liver ablation, and embolization therapy are amongst the conventional methods for treatment of HCC. Chemotherapy plays a major role in HCC therapy, however, owing to its conventional pharmacotherapy limitations, it necessitates the development of novel therapeutic strategies. In contrast, nanomedicines for HCC have shown remarkable prospects for solving these complications in HCC owing to their high stability, controlled release, and high drug loading capacity. This review gives an insight into the nano-constructs used for HCC treatment and its active and passive targeting strategies. This review also inculcates the various approaches for targeting the liver cells, its targeting moieties and the conjugation chemistries involved in surface functionalization. A brief description of various therapeutic approaches in the treatment of HCC has also been discussed

Surface architectured black phosphorous nanoconstructs based smart and versatile platform for cancer theranostics

Black Phosphorous has recently gained the attention in the field of 2D nanomaterials owing to its exceptional structure and properties. Specifically, its features like drug loading efficiency, biocompatibility, optical, mechanical, electrical, thermal and phototherapeutic properties contribute to its rising demand as potential alternative to the graphene-based 2D nanomaterials in biomedical applications. Though the BP's outlook appears promising, its practical applicability is highly challenging. In this review we have discussed the different strategies for synthesis of BP and then briefed its unique properties which renders it a potential platform for the biomedical application. We then discuss the importance of heterogeneous doping on improving the stability of BP against chemical degradation and enhancing its photoelectric properties. Meanwhile, BP-based nanoconjugates, stimuli responsive nanoplatforms, therapeutic, imaging and biosensing platforms are the domains of special and comprehensive interest for versatile biomedical applications of BP. The physicochemical interactions at the nano-bio interface like protein corona formation on the surface on nanoparticles due to interaction with the plasma proteins and others play a crucial role in the biological effects of BP. Hence, we have also discussed the recent studies on interactions between Black phosphorus based nanoconstructs with various biological molecules. Further, it is vital to consider the fact that, though biocompatible, BP-nanomaterials can induce inflammatory responses and exhibit toxicity in dose and time dependant manner. Therefore, we have briefed the biodegradation and toxicological aspects of BP to enlighten the readers about the safety and toxicity of black phosphorous. The future developments of this 2D nanomaterial will not only serve as a boon for oncology, but also functions as a potential nanoplatform for other biomedical applications.Fil: Pandey, Abhijeet. Manipal College Of Pharmaceutical Sciences; IndiaFil: Nikam, Ajinkya Nitin. Manipal College Of Pharmaceutical Sciences; IndiaFil: Padya, Bharath Singh. Manipal College Of Pharmaceutical Sciences; IndiaFil: Kulkarni, Sanjay. Manipal College Of Pharmaceutical Sciences; IndiaFil: Fernandes, Gasper. Manipal College Of Pharmaceutical Sciences; IndiaFil: Shreya, Ajjappla Basavaraj. Manipal College Of Pharmaceutical Sciences; IndiaFil: García, Mónica Cristina. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaFil: Caro, Carlos. Universidad de Málaga; EspañaFil: Páez Muñoz, Jose Maria. Universidad de Málaga; EspañaFil: Dhas, Namdev. Sres Sanjivani College Of Parmaceutical Education And Research; India. Nirma University. Institute Of Pharmacy; IndiaFil: García Martín, Maria Luisa. Universidad de Málaga; EspañaFil: Mehta, Tejal. Nirma University. Institute Of Pharmacy; IndiaFil: Mutalik, Srinivas. Manipal College Of Pharmaceutical Sciences; Indi