Phospholipid Complex Research Articles

Vitamin D3/phospholipid complex decorated caseinate nanomicelles for targeted delivery of synergistic combination therapy in breast cancer

Targeted delivery of cytotoxic drugs has shown great potential in cancer therapy. In this light, vitamin D3 (vit.D3)-coated micelles were fabricated to encapsulate the cytotoxic drug; etoposide (ETP). Sodium caseinate micelles were first utilized to encapsulate vit.D3 and ETP within their hydrophobic core, then drug-loaded micelles were further decorated with an envelope of vit.D3/ phospholipid complex to enhance the active targeting potency of fabricated micelles via exploiting vit.D3 receptors (VDRs) overexpressed on the outer surface of breast cancer cells. In vitro cytotoxicity studies showed that fabricated micelles exhibited improved anticancer effect on MDA MB-231 and MCF-7 human breast cancer cell lines in comparison to free vit.D3 + ETP without any significant toxicity on normal human lung fibroblast (Wi-38) cells. In vivo biodistribution and efficacy studies in Ehrlich ascites tumor animal model revealed that fabricated micelles manifested improved accumulation in tumor tissue due to active targeting potential of vit.D3 without any remarkable toxicity. More importantly, fabricated micelles resulted in enhanced tumor apoptosis, reduced angiogenesis, invasion and autophagy, besides a decline in the tumor expression levels of both miR-21 and miR-192. Therefore, vit.D3/ETP micelles could serve as a favorable actively targeted anticancer delivery system having a superior effect over the free combination.

Improved biopharmaceutical attributes of lumefantrine using choline mimicking drug delivery system: preclinical investigation on NK-65 P.berghei murine model

ABSTRACT Background Lumefantrine (LMF) is first-line antimalarial drug, possesses activity against almost all human malarial parasites, but the in vivo activity of this molecule gets thwarted due to its low and inconsistent oral bioavailability (i.e. 4–12%) owing to poor biopharmaceutical attributes. Methods Lumefantrine phospholipid complex (LMF-PC) was prepared by rota-evaporation method following job’s plot technique for the selection of apt stoichiometric ratios. Docking studies were carried out to determine the possible interaction(s) of LMF with phosphatidylcholine analogue. Comparative in vitro physiochemical, solid-state characterization, MTT assay, dose-response on P. falciparum, in vivo efficacy studies including pharmacokinetic and chemosuppression on NK-65 P. berghei infected mice were carried out. Results Aqueous solubility was distinctly improved (i.e. 345 times) with phospholipid complex of LMF. Cytotoxicity studies on Hela and fibroblast cell lines demonstrated safety of LMF-PC with selectivity indices of 4395 and 5139, respectively. IC50 value was reduced almost 2.5 folds. Significant enhancement in Cmax (3.3-folds) and AUC (2.7-folds) of rat plasma levels indicated notable pharmacokinetic superiority of LMF-PC over LMF suspension. Differential leukocytic count and cytokine assay delineated plausible immunoregulatory role of LMF-PC with nearly 98% chemosuppression and over 30 days of post-survival. Conclusion Superior antimalarial efficacy and survival time with full recovery of infected mice revealed through histopathological studies.

Combination of Phospholipid Complex and Matrix Dispersion.

Phospholipid complexation, despite being a successful, versatile, and burgeoning strategy, stickiness of phospholipids leads to suboptimal dissolution rate of drugs. This work was undertaken to fabricate simvastatin-phospholipid complex (SIM-PLC)-loaded matrix dispersion (SIM-PLC-MD) using Soluplus® as carrier material, to augment dispersibility and dissolution of SIM-PLC without altering complexation between simvastatin (SIM) and phospholipid. SIM-PLC and SIM-PLC-MD were prepared using solvent evaporation and discontinuous solvent evaporation techniques, respectively. The successful complexation was substantiated by FTIR method. Besides, PXRD and SEM studies disclosed the absence of crystallinity of SIM in both SIM-PLC and SIM-PLC-MD. The TEM analysis monitored the self-assembly of SIM-PLC and SIM-PLC-MD into colloidal structures, which could be correlated with redispersion in GIT fluids upon oral administration. The considerable increase in hydrophilicity of SIM-PLC-MD and SIM-PLC as evident from partition coefficient experiment can further be correlated with their remarkably improved solubility profiles in the following pattern: SIM-PLC-MD˃SIM-PLC˃SIM. Correspondingly, improved dispersibility of SIM-PLC-MD in comparison to SIM-PLC can be accountable for accelerated dissolution rate by 2.53-fold and 1.5-fold in pH 1.2 and 6.8 conditions, respectively. The oral pharmacokinetic evaluation in Sprague Dawley (SD) rats revealed 3.19-fold enhancement in oral bioavailability of SIM through SIM-PLC-MD when compared with plain SIM, whereas 1.83-fold increment was observed in the case of SIM-PLC. Finally, the efficacy experimentation in SD rats revealed that SIM-PLC-MD significantly reduced triglycerides and cholesterol levels in comparison to SIM and SIM-PLC. These outcomes suggest that a matrix dispersion strategy improves oral bioavailability and hypolipidemic activity of SIM.

Gaikwad Abhijeet R. Phytosome as a Novel Drug Delivery System for Bioavailability Enhancement of Phytoconstituents and its Applications: A Review

Phytoconstituents are used extensively in modern science due to their varied therapeutic actions with few side effects. Regardless of their excellent pharmacodynamic activity, many Phytoconstituents have shown less bioavailability in vivo. Novel drug delivery systems have gained vital importance due to their increased bioavailability, and overall therapeutics. The water miscible Phytoconstituents have excellent bioactivity in vitro, however poor or no action in vivo. Phytosome technology can overcome this drawback during which the Phyto actives are allowed to react with phospholipid molecules. The Phytoconstituents with low lipoid solubility on complexation into herbal extract. Phospholipids show high affinity for polyphenolics, and type supramolecular adducts having a certain ratio. Hydrogen bond interactions between Phytoconstituents and phospholipids enable phospholipid complexes as an integral part. Complexation of phospholipids with active constituents of plants improves their bioavailability and is being extensively studied by researchers, and additional research during this regard is predicted within the future. This review highlights the unique property of phospholipids in drug delivery, phospholipid chemistry, stoichiometric ratios. We also discuss recent progress in research on the preparation, characterization, structural verification, advantages, recent patents, marketed formulation their application to enhance the bioavailability of active herbal Phytoconstituents. Keywords: Phytosome, Novel drug delivery, Phosphatidylcholine, Bioavailability, Patents, Applications.

Bioavailability of berberine: challenges and solutions

Berberine is a quaternary benzylisoquinoline alkaloid with multiple pharmacological effects used for the treatment of hypertension, tumors, bacterial infections, inflammation, HIV, and cardiac diseases. In phase I clinical trials, berberine is safe at excessive doses but manifests poor bioavailability. Major challenges like poor absorption, rapid metabolism, and rapid systemic elimination are responsible for low plasma and tissue levels of berberine. Various strategies have been undertaken by several researchers to overcome this issue and enhance the bioavailability of berberine. This includes the design of new formulation strategies; novel drug delivery systems (NDDS) like liposomes, nanosized dosage forms, phospholipid complexes, mucoadhesive microparticles, and micoemulsions; the use of adjuvants; and the design of structural analogous of berberine. This review focuses on the occurrence of berberine in numerous plants and its pharmacological activities as evidenced through numerous preclinical and clinical studies. The later part of this review highlights the bioavailability issue of berberine which arises due to its poor absorption, elevated rate and extent of metabolism, and quick elimination and clearance from the body. A systematic effort has beenmade to analyze the various formulation strategies, including the design of newer berberine analogues and derivatives. These strategies can be further explored to increase the bioavailability, medicinal value, and application of this promising molecule.

Pegylated liquisomes: A novel combined passive targeting nanoplatform of L-carnosine for breast cancer

PEGylated Liquisomes (P-Liquisomes), a novel drug delivery system was designed for the first time by incorporating phospholipid complex in PEGylated liquid crystalline nanoparticles (P-LCNPs). L-carnosine (CN), a challenging dipeptide, has proven to be a promising anti-cancer drug. However, it exhibits high water solubility and extensive in-vivo degradation that halts its use. The objective of this work was to investigate the ability of our novel system to improve the CN anticancer activity by prolonging it’s release and protecting it in-vivo. In-vitro appraisal revealed spherical light-colored vesicles encapsulated in the liquid crystals, confirming the successful formation of the combined system. P-Liquisomes were nano-sized (149.3 ± 1.4 nm), with high ZP (−40.2 ± 1.5 mV), complexation efficiency (97.5 ± 0.9%) and outstanding sustained release of only 75.4% released after 24 h, compared to P-LCNPs and Phytosomes. The results obtained with P-Liquisomes are considered as a break through compared to P-LCNPs or Phytosomes alone, especially when dealing with the hydrophilic CN. In-vitro cytotoxicity evaluation, revealed superior cytotoxic effect of P-Liquisomes (IC50 = 25.9) after 24 h incubation. Besides, P-Liquisomes proved to be non-toxic in-vivo and succeeded to show superior chemopreventive activity manifested by reduction of; % tumor growth (7.1%), VEGF levels (14.3 pg/g tissue), cyclin D1 levels 15.5 ng/g tissue and elevation in caspase-3 level (36.4 ng/g tissue), compared to Phytosomes and CN solution. Conclusively, P-Liquisomes succeded to achieve the maximum therapeutic outcome of CN without altering its activity and might be used as a sustained delivery system for other promising hydrophilic compounds.

Preparation and Evaluation of a Self-Nanoemulsifying Drug Delivery System Loaded with Heparin Phospholipid Complex.

A self-nanoemulsifying drug delivery system (SNEDDS) was developed to enhance the absorption of heparin after oral administration, in which heparin was compounded with phospholipids to achieve better fat solubility in the form of heparin-phospholipid (HEP-Pc) complex. HEP-Pc complex was prepared using the solvent evaporation method, which increased the solubility of heparin in n-octanol. The successful preparation of HEP-Pc complex was confirmed by differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR) spectroscopy, NMR, and SEM. A heparin lipid microemulsion (HEP-LM) was prepared by high-pressure homogenization and characterized. HEP-LM can enhance the absorption of heparin after oral administration, significantly prolong activated partial thromboplastin time (APTT) and thrombin time (TT) in mice, and reduce fibrinogen (FIB) content. All these outcomes indicate that HEP-LM has great potential as an oral heparin formulation.

Potential Of Curcumin Loaded Nanoparticles In Antimicrobial Photodyanamic Therapy

In the past decade, multi-drug resistance of pathogenic bacteria has become a serious problem to public health. Finding novel approaches to combat multi-drug resistant bacteria have therefore become increasingly important. One promising approach is antimicrobial photodynamic therapy (aPDT) which involves the use of photo-sensitizer (nontoxic dyes) that are excited by visible light and produce oxygen free radicals in the presence of oxygen. Many studies report that curcumin inhibits the growth of both gram-positive and gram-negative bacteria. Formulations of curcumin in liposome, nanoparticles, micelles and phospholipids complexes are being prospected to decline its hydrophobicity, increase solubility to amplify blood flow time, and its permeability through membrane barriers. Among these options nano-formulations of curcumin such as nano-crystals, nano-emulsions and polymeric nanoparticle encapsulated curcumin got enormous thrust and advance in the recent years in the category of natural or herbal drugs.. There are evidences that support the enhancement of antimicrobial activity and antibiofilm activities of curcumin silica nanoparticles of P.aeruginosa and S.aureus cultures using aPDT. This therapy exhibits significant antimicrobial activity against both bacteria. This review provides an updated information regarding the use of natural products to limit or prevent microbial resistance through use of photosensitizing agents like curcumin.

Development of phospholipid complex loaded self-microemulsifying drug delivery system to improve the oral bioavailability of resveratrol.

Aim: The aim of this study was to develop a formulation that combines a phospholipid complex (PC) and self-microemulsifying drug delivery system (SMEDDS) to improve the bioavailability of poorly water-soluble resveratrol (RES), called RPC-SMEDDS. Methods: RES-PC (RPC) and RPC-SMEDDS were optimized by orthogonal experiment and central composite design, respectively. The characteristics and mechanism of intestinal absorption were studied by Ussing chamber model. The pharmacokinetics was evaluated in rats. Results: RES was the substrate of MRP2and breast cancer resistance protein(BCRP)rather than P-gp. The prepared RPC-SMEDDS prevented the efflux mediated by MRP2 and BCRP and improved the bioavailability of RES. Conclusion: These results suggested that the combination system of PC and SMEDDS was a promising method to improve the oral bioavailability of RES.

Fabrication of oral nanovesicle in-situ gel based on Epigallocatechin gallate phospholipid complex: Application in dental anti-caries

The conventional anti-caries agents exhibit many shortcomings such as poor stability, low efficacy or short residence time in the oral environment, it is urgent to develop efficacy treatments to prevent dental caries. As the most active polyphenols from tea, Epigallocatechin gallate (EGCG) shows remarkable anti-cariogenic bioactivity. However, the poor stability and low bioavailability of EGCG limit its potential application. This study aimed to fabricate nanovesicles in-situ gel based on EGCG phospholipid complex in order to increase its stability and efficacy. The formation of EGCG phospholipid complex was characterized by Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The ethanol injection method was used to prepare the EGCG-loaded nanovesicles, an optimal ratio of Poloxamer407 (P407) and Poloxamer188 (P188) as in-situ gel matrix was selected to fabricate oral nanovesicles in-situ gel. EGCG-loaded nanovesicle in-situ gel based on the phospholipid complex had uniform spherical shape without any agglomeration. The discrete nanoparticle with a size (131.44 ± 4.24 nm) and a negative zeta potential value at −30.7 ± 0.5 mV possessed good physical stability and high entrapment efficiency (83.66 ± 3.2%). The formulation exhibited a strong antibacterial activity on S. mutans, which could reduce acid production and tooth surface adhesion. In addition, EGCG formulation could inhibit the formation of glucan and biofilm from S. mutans by suppressing the activity of glycosyltransferase enzymes (GTF). In conclusion, the EGCG-loaded nanovesicle in-situ gel holds great promise as an efficient anti-cariogenic formulation for topical oral delivery.

Preparation, Characterization and In Vitro Antioxidant Potential of Boldine-phospholipid Complex

Background: Boldine, is an aporphine alkaloid that possesses potent antioxidant activity. Despite having enormous potential, the clinical application of boldine was restricted because of its poor bioavailability attributed to its poor aqueous solubility and rapid clearance from the body. The drug phospholipid complexation techniques were frequently employed to overcome the limitation of low bioavailability of phytoconstituents/herbal extract. Objective: The boldine phospholipid complex (BOL-PC) formulation was developed for enhancing antioxidant potential of boldine by preparing its phospholipid complex. Methods: Boldine loaded phospholipid (BOL-PC) complex was prepared by refluxing followed by solvent evaporation method and subjected to various physicochemical and spectral analysis. Further, the in-vitro antioxidant activity was evaluated by DPPH free radical scavenging method. Results: The formation of the complex was confirmed by 1H NMR and thermal analysis. SEM and PXRD revealed partial amorphization of drug in complex formed. The BOL-PC dissolution rate and solubility was significantly improved compared to the parent compound. The maximum % yield and % EE was found to be 95.92± 0.01732 and 95.89±0.3502 respectively in the optimized formulation (F3) which exhibited concentration-dependent antioxidant property. Conclusion: It was concluded from the study that the phospholipid complexation of boldine has better antioxidant potential and improved the solubility, dissolution profile which may facilitate its oral absorption and enhances its chances for clinical application.

Improving Breviscapine Oral Bioavailability by Preparing Nanosuspensions, Liposomes and Phospholipid Complexes.

Breviscapine (BVP), a flavonoid compound, is widely used in the treatment of cardiovascular and cerebrovascular diseases; however, the low oral bioavailability and short half-life properties limit its application. The aim of this study was to investigate the three preparations for improving its oral bioavailability: nanosuspensions (BVP-NS), liposomes (BVP-LP) and phospholipid complexes (BVP-PLC). In vitro and in vivo results suggested that these three could all significantly improved the cumulative released amount and oral bioavailability compared with physical mixture, in which BVP-PLC was the most optimal preparation with the relative bioavailability and mean retention time of 10.79 ± 0.25 (p < 0.01) and 471.32% (p < 0.01), respectively. Furthermore, the influence of drug-lipid ratios on the in vitro release and pharmacokinetic behavior of BVP-PLC was also studied and the results showed that 1:2 drug-lipid ratio was the most satisfactory one attributed to the moderate-intensity interaction between drug and phospholipid which could balance the drug loading and drug release very well.

Use of combined nanocarrier system based on chitosan nanoparticles and phospholipids complex for improved delivery of ferulic acid

A novel nanocarrier system of phospholipids complex loaded chitosan nanoparticles (FAPLC CNPs) was developed to improve the oral bioavailability and antioxidant potential of FA. FAPLC CNPs were optimized using a Box-Behnken Design (BBD). FAPLC CNPs were characterized using differential scanning calorimetry, Fourier transforms infrared spectroscopy, powder x-ray diffractometry, proton nuclear magnetic resonance, solubility, in vitro dissolution, ex vivo permeation, and in vivo antioxidant activity in carbon tetrachloride (CCl4)-induced albino rat model. The characterization studies indicated a formation of the complex as well as FAPLC CNPs. The FAPLC CNPs exhibited a lower particle size ~123.27 nm, PDI value ~0.31, and positive zeta potential ~32 mV respectively. Functional characterization studies revealed a significant improvement in the aqueous solubility, dissolution, and permeation rate of FAPLC and FAPLC CNPs compared to FA and FA CNPs. The FAPLC CNPs showed significant enhancement of in vivo antioxidant activity of FA by restoring the elevated marker enzymes in the CCl4-intoxicated rat model compared to FA CNPs. Moreover, the pharmacokinetic analysis demonstrated a significant enhancement of oral bioavailability of FA from FAPLC CNPs compared to FA CNPs. These findings show that FAPLC CNPs could be used as an effective nanocarrier for improving the oral delivery of FA.

Development and evaluation of puerarin-loaded controlled release nanostructured lipid carries by central composite design

The present work was aimed at developing optimized puerarin-loaded nanostructured lipid carrier (PA-NLC) on base of phospholipid complex. The puerarin phospholipid complex (PA-PC) was prepared by a solvent evaporation method and the formulation was confirmed according to the encapsulation efficiency (EE%). The hepatoprotective effect of PA-NLC on BRL 3A cell stimulated by ethanol was carried out using MTT assay, and cell imaging was done using an inverted phase contrast tissue culture microscope. The NLCs were produced by nanoemulsion method using glyceryl monostearate (GMS), olive oil, and Poloxamer 188 as the solid, liquid lipids, and surfactant. A single factor analysis determined the optimal ratio of solid lipid to liquid lipid. A three-factor, five-level central composite design (CCD) was used to predict response variables and construct 3D-response contour plots. The independent variables, which were the concentrations of PA-PC, total lipid, and surfactant affected particle size, surface charge of the nanoparticles, and the EE. An optimized NLC composition consisted of 31.25% PA-PC, 46.87% GMS, 9.38% olive oil, and 18.75% Poloxamer 188. The NLC had an average particle size of 159 ± 1.1 nm, zeta potential of −28.3 mV, EE% of 92.16%, and drug loading (DL%) of 5.75%. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) studies showed that the formation of NLC was accompanied by changes in crystallinity and intermolecular interaction. The PA-NLC system showed an enhanced therapeutic effect on alcohol-induced cell injury of BRL-3A.

Transdermal delivery of triptolide–phospholipid complex to treat rheumatoid arthritis

The aim of this study was to develop and evaluate a triptolide phospholipid complex (TPCX) for the treatment of rheumatoid arthritis (RA) by transdermal delivery. TPCX was prepared and characterized by differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR) analysis, transmission electron microscope (TEM), and scanning electron microscope (SEM). The solubility of TPCX was determined. Then, a TPCX cream was prepared to evaluate its percutaneous permeability and the antiarthritis effect. The transdermal permeability was determined using the Franz method, and a microdialysis system was used for skin pharmacokinetic study. A rat model of RA was prepared to evaluate the pharmacological effects. TPCX increased the solubility of triptolide in water, and the percutaneous permeability of TPCX cream was greatly enhanced compared with triptolide cream. The skin pharmacokinetic study indicated that TPCX cream has a longer biological half-life (t 1/2) and mean residence time (MRT), but it has a shorter T max than that of triptolide cream in vivo. The area under the curve (AUC0– t )/AUC0–∞) and the peak concentration (C max) of TPCX cream were obviously higher than those of triptolide cream. The TPCX-loaded cream alleviated paw swelling and slowed down the progression of arthritis by inhibiting the inflammatory response by down regulating the TNF-α, IL-1β, and IL-6 levels, thus exhibiting excellent antiarthritic effects. In summary, the prepared TPCX effectively increases the hydrophilicity of triptolide, which is good for its percutaneous absorption and enhances its effect on RA rats. TPCX can be a good candidate for the transdermal delivery to treat RA.

Phytophospholipid Complex of Caffeic Acid: Development, In vitro Characterization, and In Vivo Investigation of Antihyperlipidemic and Hepatoprotective Action in Rats

Caffeic acid (CA), a hydroxycinnamic acid possessing a variety of pharmacological activities, has caused a growing interest for the treatment of hyperlipidemia and associated conditions. This work endeavored to develop a novel formulation of CA-Phospholipon® 90H complex (CA-PC) using a solvent evaporation method. Scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared spectrophotometry (FTIR), and powder X-ray powder diffraction (PXRD) was carried to confirm the formation of CA-PC. The CA-PC was functionally evaluated in terms of solubility, in vitro and ex vivo drug release, and in vivo bioavailability and efficacy studies. SEM, DSC, FTIR, and XRD studies indicated the physical interaction of CA with Phospholipon® 90H to form a complex. Dynamic light scattering (DLS) studies described particle size of 168 ± 3.9nm with a monodisperse distribution (PDI 0.17) and a negative zeta-potential of - 16.6 ± 2.1mV. The phospholipid complex significantly improved (4.2-fold) the solubility of CA. In vitro and ex vivo dissolution studies of the formulated CA-PC revealed a significantly higher release compared with the pure CA. The pharmacokinetic study of CA-PC in rats demonstrated a significant increase (4.79-fold) in oral bioavailability when compared with pure CA as well. Additionally, a significant improvement in serum lipid profile, serum liver biomarker enzyme levels and, restoration of hepatic tissue architecture to normal, in high-fat diet (HFD) induced hyperlipidemic model was obtained upon CA-PC administration when compared with pure CA. These findings indicated that CA-PC would serve as an effective and promising formulation for CA delivery with improved antihyperlipidemic and hepatoprotective activity.Graphical abstract.

Development and characterization of a nano-drug delivery system containing vasaka phospholipid complex to improve bioavailability using quality by design approach.

Background and purpose:Vasicine is a potential bronchodilator and can be used for the effective management of asthma and bronchitis. It has low absorption in the gastrointestinal tract due to its poor solubility thereby low bioavailability. The objective of this research was to develop a novel drug delivery system of vasaka extract to improve its bioavailability by enhancing the solubility and absorption of vasicine.Experimental approach:Vasaka-loaded phytosomes were developed and optimized by thin-layer hydration technique using systematic quality by design approach. Box-Behnken design (32 factorial design) using Design-Expert software was employed to optimize phytosome wherein phosphatidylcholine concentration (X1), stirring temperature (X2), and stirring time (X3) were selected as independent variables. Yield (%), particle size (nm), and entrapment efficiency (%) were evaluated as responses. The optimized phytosome was characterized by studying the surface morphology such as FE-SEM and TEM analysis, thermal characteristics by thermal gravimetric analysis and spectral and diffraction studies by FTIR and XRD analysis and studying the dissolution behaviour of phytosome by in vitro release study.Findings/Results:The percentage yield, particle size, and entrapment efficiency values of the phytosomes were found in the range of 30.03-97.03%, 231.0-701.4 nm, and 20.02-95.88% w/w, respectively. The optimized phytosome showed the zeta potential of -23.2 mV exhibited good stability and SEM and TEM analysis revealed the spherical shape and smooth particles with the uniform particle size distribution of phytosomes. The comparative in vitro drug release study of vasaka extract and phytosome revealed the sustained release characteristics of phytosome which reached 68.80% at 8 h compared to vasaka extract reached a maximum of 45.08% at 4 h.Conclusion and implication:The results highlighted the importance of optimization of formulation development using quality by design strategy to achieve consistent quality of pharmaceutical products.

Preparation and Evaluation of Glaucocalyxin A SustainedRelease Pellets Based on Phospholipid Complex System with Enhanced Bioavailability

Preparation and Evaluation of Glaucocalyxin A SustainedRelease Pellets Based on Phospholipid Complex System with Enhanced Bioavailability

A novel nanosized phospholipid complex of Biochanin A for improving oral bioavailability: Preparation and in-vitro/in-vivo characterizations

Biochanin A (BCA) is a natural methoxylated-isoflavone and has been stated to have various therapeutic potentials. However, poor aqueous solubility and low oral bioavailability circumscribed its usage as a therapeutic molecule. Therefore, nano-sized BCA-phospholipid complex (nBCA-PLCs) was developed using solvent evaporation and ultra-sonication method to enhance the poor aqueous solubility and low oral bioavailability of BCA. The optimized nBCA-PLCs showed monodisperse spherical particles with a mean diameter of 329.63 ± 35.71 nm (PDI 0.288 ± 0.03), the zeta potential of (−) 53.9 ± 1.24 mV and drug entrapment efficiency of about 94.62 ± 4.19%. In vitro release study revealed that more than 99% drug was released from developed nBCA-PLCs. The formation of nBCA-PLCs complex and the loss of a crystalline state of BCA in the developed formulation were confirmed by solid-state characterizations including DSC, FTIR, and powder XRD. In situ single-pass intestinal permeability (SPIP) study showed a significant increase (2.04 fold) in the effective intestinal permeability (Peff) of BCA from nBCA-PLCs as compared with plain BCA suspension. Similarly, the oral administration of BCA-PLCs and nBCA-PLCs in Sprague Dawley (SD) rats showed 2.4-fold and 7.2 fold increase in relative bioavailability of BCA from BCA-PLCs and nBCA-PLCs, respectively as compared with plain BCA suspension. Thus, the developed nBCA-PLCs can be promising to overcome the poor aqueous solubility and increase the oral bioavailability of this poorly aqueous soluble molecule.

Development and Optimization of Epigallocatechin-3-Gallate (EGCG) Nano Phytosome Using Design of Experiment (DoE) and Their In Vivo Anti-Inflammatory Studies.

Inflammation is responsible for the development of many diseases that make up a significant cause of death. The purpose of the study was to develop a novel nanophytosomal preparation of epigallocatechin-3-gallate (EGCG) and egg phospholipid complex that has a lower particle size with higher drug loading capability, physical stability and anti-inflammatory activities. The impact of different factors and material characteristics on the average particle size was studied along with the drug loading of phytosome using design of experiment (DoE). The in vivo anti-inflammatory study was evaluated using a rat model to investigate the performance of EGCG nanophytosome. UHPLC results showed that 500 µg of EGCG were present in 1 mL of green tea extract. SEM data exhibited that phytosome (phospholipid-drug complex) was in the nanosize range, which was further evident from TEM data. Malvern Zetasizer data showed that the average particle size of the EGCG nanophytosome was in the range of 100–250 nm. High drug loading (up to 90%) was achieved with optimum addition rate, stirring temperature and phospholipid concentration. Stability study data suggest that no significant changes were observed in average particle size and drug loading of nanophytome. The in vivo anti-inflammatory study indicated a significant anti-inflammatory activity of green tea extract, pure EGCG and its phytosomal preparations (p ≤ 0.001) against acute paw edema.