Plain Drug Research Articles

DEVELOPMENT AND EVALUATION OF SELF EMULSIFIED DRUG DELIVERY SYSTEM OF EMBELIN FOR THE TREATMENT OF AMOEBIASIS

Objective: Development and evaluation of self-emulsified drug delivery system of embelin for the treatment of amoebiasis. Methods: Self-emulsifying drug delivery systems (SEDDS) were prepared by determining the saturation solubility of embelin in different oil, surfactant and co-surfactant. Pseudo-ternary phase diagram was prepared by using chemix software for the selection of surfactant and co-surfactant ratio, and was optimized as 2:1 (Surfactant: Co-surfactant) for SEDDS. The drug was dissolved in surfactant, followed by the addition of co-surfactant and oil in a beaker. The resultant mixtures were stirred continuously by magnetic stirrer and heated at 40 °C to obtain a homogenous mixture. The prepared drug-loaded SEDD formulation was optimized on the basis of emulsification time, size, PDI, zeta potential and precipitation of drugs. Then the anti-amoebic activity of embelin and metronidazole-loaded SEDDS powder was carried out using microplate reader. Results: The optimum solubility of embelin was calculated in Capmul MCM EP as oil (37 mg/ml), Kolliphor hs 15 as surfactant (150 mg/ml) and PEG 400 as co-surfactant (19 mg/ml). The formulation F7 i.e. 70% Smix and 30% oil was estimated as optimized formulation. The different values of emblein loaded SEDDS was found to be dilution test (no sign of precipitation), centrifugation test (no sign of phase separation), globule size (Dia 217.5 nm) and PDI (108), zeta potential determination (-31.60 mV), viscosity (17.12 cps) and Eosin red confirmed the o/w type of emulsion. Moreover, the angle of repose SEDDS prepared by using Avicel 200 was found to be Θ=27.474, means flow of powder is good with drug loading capacity of 92.7 %. SEM image and in vitro drug release indicated the 99.3% drug was released from the SEDDS in 120 min. Cytotoxicity study (MTT assay) shows the Plain Drug Suspension, Embelin loaded SEDDS powder and Metronidazole exhibited 100% viability at the concentration range of 1.56-100 mmol. The anti-amoebic IC50 values of embelin, metronidazole and embelin loaded SEDDS powder was found 1.519 µmol, 1.354 µmol, 1.84 µmol and 1.35 µmol, respectively. Conclusion: Present study showed the stronger amoebicidal action of embelin may associated with some specific interaction of the active embelin with the cell wall of the parasites or with a more effective mechanism of penetration into the parasites through membrane channels.

Microwave-Assisted Fabrication of Cyclodextrin-Based Nanosponges for Solubility Enhancement

Cinnarizine is plagued by low aqueous solubility and thereby poor bioavailability. Thus, it could be a model drug whose bioavailability can be improved by enhancing its solubility. The present study focuses on the fabrication of cyclodextrin-based nanosponges using a microwave-assisted approach. Phase solubility studies were performed to shortlist the cyclodextrin. The manufacturing process was streamlined by applying the 3-factor, 3-level Box-Behnken experimental design to optimize the microwave power level, reaction time, and stirring speed. The batch with the least particle size and highest yield was finalized. The prepared nanosponges were characterized for particle size, polydispersity index, zeta potential, drug loading, entrapment efficiency, and FTIR spectroscopy. The in-vitro drug release showed a drastic improvement in the solubility and release of cinnarizine from the nanosponges as compared to that of the plain drug and drug-cyclodextrin physical mixture. The study proved the suitability of this system for the solubility enhancement of cinnarizine.

Formulation and evaluation of proliposomal tablet of Diclofenac sodium

Proliposomes were successfully formulated using film deposition on carrier technique and characterized for percentage yield, drug content, size, PDI, zeta potential, flow properties, TEM, and in vitro drug release. Proliposome tablet was prepared by directly compressing the powder and evaluated for general appearance, weight variation, thickness, diameter, hardness, friability, disintegration time, in-vitro dissolution, assay, in-vivo gastric damage study, liposome size after reconstitution, pharmacokinetic study and stability study. Percentage yield and drug content of proliposome powder were found to be 95.10% and 91.54% respectively. Vesicular Size, PDI, zeta potential and entrapment efficiency of liposomes were found to be 231 nm, 0.477, −25.0 mV and 68.02% respectively. Diclofenac sodium loaded proliposome tablet showed 1.95 times higher bioavailability compared to plain enteric coated tablet of Diclofenac sodium. In vivo gastric damage study indicated that prepared Diclofenac sodium loaded proliposome tablets exhibited higher bioavailability and was safer compared to plain drug.

Cocrystal Formulation: A Novel Approach to Enhance Solubility and Dissolution of Etodolac

Etodolac (ETD) is a non-steroidal anti-inflammatory drug (NSAID) given in rheumatoid arthritis treatment. As it comes under BCS class II drug hence it exhibits low water solubility. Also, its dissolution rate-limited oral absorption results in delayed onset of action. The Novel approach in the solubility enhancement field; crystal engineering was preferred to prepare pharmaceutical cocrystals of etodolac with GRAS (generally recognized as safe) molecules. Pharmaceutical cocrystals of etodolac were prepared with p-hydroxybenzoic acid and glutaric acid with the drug: coformer ratio 1:1 and 1:2. Cooling cocrystallization was used to prepare etodolac cocrystals. Cocrystal formulations were characterized by saturation solubility study, in-vitro dissolution studies, and stability study. Cocrystal was also characterized by analytical parameters like Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). Optimized Cocrystal formulation dissolved more rapidly and their equilibrium solubility is greater than the plain drug.

3D nanocomposite alginate hydrogel loaded with pitavastatin nanovesicles as a functional wound dressing with controlled drug release; preparation, in-vitro and in-vivo evaluation

Nanocomposite alginate hydrogel containing pitavastatin nanovesicles were prepared as a bioactive wound dressing. Nanovesicles were formed via thin-film hydration technique using different types of lipids and sodium deoxycholate as a surfactant. Nanovesicles were evaluated for entrapment efficiency, particle size, zeta potential, in-vitro drug release besides their morphological properties. Nanovesicles were optimized applying 41 × 22 mixed factorial design using Design-Expert® VR software. The optimum formulation, composed of 400 mg Lipoid S45 and 0.1%w/v sodium deoxycholate, showed the highest entrapment efficiency (87.1 ± 0.3%) and drug release up to 3 days. Nanocomposite hydrogel was fabricated by incorporating the selected nanovesicles into calcium alginate hydrogel. The nanocomposite hydrogel was evaluated for water absorption capacity and in-vitro release besides in-vivo studies on dogs. Results revealed that the nanocomposite hydrogel possessed the highest water uptake at 21 days and the drug release was sustained up to 7 days. In-vivo studies on surgically induced skin wounds proved the success of the nanocomposite alginate hydrogel in promoting wound healing and wound closure. Histopathological studies revealed the superiority of nanocomposite hydrogel over plain hydrogel and drug suspension regarding the fast and proper rejuvenation of damaged skin layers. In conclusion, nanocomposite alginate hydrogel loaded with pitavastatin provided a promising, safe line for wound healing purposes.

Effect of Capecitabine Resealed Erythrocytes on MNU Induced Hepatocarcinogenesis in Swiss Albino Mice

Rationale of the study: Capecitabine is potential anticancer prodrug approved for colorectal cancer and metastatic breast cancer. It has short half life and several adverse effects due to which was encapsulated in erythrocytes for the treatment of hepatocellular carcinoma to observe and compare the effect of formulation with that of plain drug. 
 Introduction: The hepatoprotective potential of Capecitabine resealed erythrocytes was evaluated using MNU induced hepatocarcinogenesis in swiss albino mice model of 4 weeks. 
 Methodology: In present study, the effects of formulation and plain drug with respect to body weight, haematological parameters, biochemical parameters and histopathological study were evaluated and compared. 
 Results: Formulation restored the normal body weight and liver architecture with slight differences. Except platelets and neutrophils, no significant differences were observed in haematological parameters. The values of antioxidant enzymes (SOD, Catalase) and AFP were also restored more with formulation than plain drug though with no statistical differences when compared with normal control. Also it reduced the lipid peroxidation in the liver in treated group Vs induced group. 
 Conclusion: All these findings demonstrated hepatoprotective and anticancer effect of Capecitabine Resealed Erythrocytes (CRE) and suggested the use of this sustained release formulation in cancer chemoprevention.

Potential of transpapillary route for artesunate-loaded microneedles against breast cancer cell line

Breast cancer is the most common cancer in women with highest mortality rate wherein, mastectomy, lumpectomy, radiation therapy, hormone therapy, chemotherapy, and biological therapy are some of the current therapeutic alternatives for breast cancer. The treatments, however, are linked to short and long-term side effects like cardiac problems, anemia, physiological distress, myelosuppression, peripheral neuropathy and thrombosis. Hence, the transpapillary route is a promising route for delivering drugs directly to the underlying breast tissues for the treatment of breast cancer by achieving higher drug levels at the tumor site. The aim of the present study was to check the potential of transpapillary route for artesunate-loaded microneedles, solid lipid nanoparticles (SLN)-loaded microneedles and layer-by-layer (LBL)-coated SLN-loaded microneedles against breast cancer. SLNs were prepared by hot-melt emulsification method and LBL-coating on SLNs was achieved by 1 mg/1 mL of chitosan and 2 mg/mL of hyaluronic acid. The particle sizes of selected formulations of SLNs and LBL-coated SLNs were found to be 213.72 ± 2.53 nm and 319.39 ± 1.25 nm, respectively. Zeta potentials of selected formulations SLNs and LBL-coated SLNs were found to be −27.32 ± 4.45 mV and −28.41 ± 3.67 mV, respectively. Three formulations of microneedles were prepared for comparative evaluation using artesunate, SLNs, LBL-coated SLNs. Microneedles were evaluated for FTIR, DSC, mechanical insertion property, surface morphology, in-vitro release, ex-vivo release and cell line studies. The cell line study and ex-vivo release profile of LBL-coated SLN microneedles showed a reduction in growth of cell line MCF 7 by 7.92 ± 1.54% and higher ex-vivo release (84.75 ± 2.02%) in comparison to plain drug. Thus, the LBL-coated SLNs microneedles of artesunate proved as an effective alternative against breast cancer cell line.

Solid Dispersion of Artemether in Fast Disintegrating Tablet to Enhance Dissolution Rate and Oral Bioavailability

Abstract: Objectives: Artemether (ART), an antimalarial drug, have poor solubility and low bioavailability. Therefore, solid dispersion of the drug was formulated using Soluplus (SOL) and was incorporated in the fast disintegrating tablet. Materials and Methods: The solid dispersion (SD) was prepared using the solvent evaporation method using a rotary evaporator. The optimized SD was evaluated and then incorporated into the tablet. Results: Solubility studies revealed that ART SD A3 of ratio 1:3 (ART: SOP) showed a significantly higher solubility and dissolution rate than plain ART. FTIR results indicated that there was no incompatibility between the drug and hydrophilic carrier. The DSC as well as XRD studies indicated the transformation from crystalline state of drug into the amorphous form. SEM studies revealed the deposition of ART on the surface of the hydrophilic carrier. In-vitro antimalarial activity was improved of the ART due to the SD formulation. Fast disintegrating tablet of ART SD A3 was produced by using directly compressible excipients such as Ludiflash and Ludipress. Ludiflash containing tablet showed fast disintegration with higher drug release. The pharmacokinetic study in mice showed increased Cmax and AUC0–24 by 1.88- and 3.19-fold as compared to those of plain drug. Conclusion: The prepared SDs using SOP provided a platform for increased solubility and also improved the bioavailability of ART with feasibility for tablet formulation. Key words: Artemether, Solid dispersion, Fast disintegrating tablet, Malaria, in-vivo study.

Liposome mediated topical delivery of Ibrutinib and Curcumin as a synergistic approach to combat imiquimod induced psoriasis

Psoriasis is an autoimmune dermal disorder characterized by the emergence of red patches, scaling and does not have any proficient therapeutic option. The study involves the investigation of synergistic effect of topical liposomal gel of Ibrutinib with Curcumin in the management of psoriasis. In the present study, liposomes were prepared and optimized (particle size 128.53 ± 1.18 nm and PDI of 0.174 ± 0.08). The prepared liposomes demonstrated high entrapment efficiency (83.15 ± 1.91% for Ibrutinib and 86.69 ± 3.80% for Curcumin) with controlled release of drug. The liposomal formulation showed the CI value of 0.214 that suggested synergism. The formulation was further loaded into 1% carbopol gel and evaluated for anti-psoriatic activity. In our study, we found that the liposomal gel containing both the drugs remarkably decreased the epidermal hyperplasia induced by the Imiquimod, ear thickness, psoriasis area, and severity index and also reduced the amount of inflammatory cytokines when compared with individual drug formulation and plain drug gel. Moreover, the histopathological evaluation revealed that topical treatment with liposomal gel eloquently decreased the lesions due to psoriasis involving acanthosis. Our findings suggest that Ibrutinib and Curcumin-loaded liposomal gel may have intriguing therapeutic potential with synergistic effects in treating psoriasis.

ANTIBACTERIAL ACTIVITY OF CHLOROGENIC ACID PHYTOVESICLES AGAINST RESISTANT BACTERIA: DEVELOPMENT, OPTIMIZATION AND EVALUATION

Objective: To investigate the in vitro antibacterial activity of a naturally occurring polyphenol chlorogenic acid (CGA) and compares it with formulated chlorogenic acid phytovesicles against 4 different bacterial strains; two gram positive [Staphylococcous aureus and Bacillus subtilis] and two gram negative strains [Klebsiella pneumonia and Escherichia coli]. Methods: CGA phytovesicles were developed and optimized using central composite design to improvise CGA’s physicochemical properties. Bactericidal activity was evaluated using agar diffusion, minimum inhibitory concentration (MIC) and time kill assay. The effect of pH and temperature on the antimicrobial activity was determined. Results: The optimized CGA phytovesicles showed entrapment of 96.89% with 30 times better lipophilic solubility than the plain drug. The inhibition zone sizes for CGA phytovesicle ranged from 17-25 mm as compared to 15-20 mm of plain CGA while the MIC values ranged 200-250 µg/ml as compared to 500-550 µg/ml of plain CGA. CGA phytovesicles exhibited a strong bactericidal effect at MIC with a log reduction in the range of 0.90-2.04 in Colony forming units (CFUs) at 24h for different strains as compared to 1.38-2.17 of plain CGA. Furthermore, the antibacterial effect was found to augment with increasing temperature but decreased with alkaline pH. Conclusion: Results strongly supports the hypothesis of potential use of CGA phytovesicles as a mode of drug delivery for its antibacterial use against different resistant bacteria.

In vivo Anticoagulant Activity of Immediate Release Tablets of Dabigatran Etexilate Mesylate Cocrystals

Dabigatran Etexilate Mesylate (DEM), a salt of prodrug dabigatran etexilate, is a potent, oral, reversible and direct thrombin inhibitor with low oral bioavailability. The present research investigation focused on the formulation of immediate release (IR) tablets of DEM cocrystals and evaluation of In vivo anticoagulant activity. The results of the study showed that the formulated IR tablets of DEM showed improved efficacy in comparison with the plain drug by enhancing the pre-compression parameters such as bulk density, tap density, Carr's index, angle of repose and Hausner's ratio and post-compression parameters like thickness and weight variation, hardness and friability, In vitro dissolution parameters. The improved efficacy was confirmed by improvement in the pharmacodynamic parameters such as cutaneous bleeding time and clotting time indicative of enhanced bioavailability of dabigatran. Thus, it can be concluded that the IR tablets of dabigatran cocrystals can be proven to be more effective in producing the anticoagulant effect in clinical practice as compared to the plain drug resulting in more patient compliance.

Ten-year trends in adverse drug reaction-related hospitalizations among people with dementia.

Aim:Trends in the incidence of adverse drug reaction (ADR)–related hospitalizations have been studied in the general population, but not specifically in people with dementia. This study aimed to investigate trends in the incidence of ADR-related hospitalizations among people with dementia, and identify the most commonly implicated drugs and diagnoses in these admissions.Methods:This study utilized the administrative data of all adults admitted to the four major public hospitals of Tasmania, Australia, with a primary or secondary diagnosis of dementia from July 2010 to December 2019. ADR-related hospitalizations were identified by using diagnosis-based and external cause codes. The Cochran–Armitage test was used to examine trends in the incidence of ADR-related hospitalizations.Results:Of the 7552 people with dementia admitted to the hospital at least once within the study period, 1775 (23.5%) experienced at least one ADR-related hospitalization. The estimated annual incidence of ADR-related hospitalizations increased 18% (1484–1760 per 100,000 population with dementia, p for trend <0.05) from 2010 to 2019. For those ADR-related admissions with a drug code recorded, 19.3% were due to antithrombotics and 11.5% to antihypertensives. The most frequent ADR-related admission diagnoses were renal diseases (72.9%). Length of hospital stay and in-hospital mortality were both significantly greater for ADR-related, relative to non-ADR-related, admissions (median 7 versus 5 days and 11% versus 6.7%, respectively; p < 0.001).Conclusion:The annual incidence of ADR-related hospitalizations in people with dementia increased between 2010 and 2019. Antithrombotics were the most commonly implicated drug class. The ADR-related hospitalizations were associated with increased length of stay and greater mortality.Plain Language Summary Adverse drug reaction–related hospitalizations among people with dementia Introduction:This study aimed to investigate trends in hospitalizations associated with medication problems among people with dementia, and identify the most commonly implicated drugs and diagnoses in these admissions.Methods:This study utilized the administrative data of all adults admitted to the four major public hospitals of Tasmania, Australia, with dementia from July 2010 to December 2019.Results:The annual incidence of hospitalizations associated with medication problems among people with dementia increased nearly 20% over 10 years. The length of hospital stay and in-hospital mortality were significantly greater for hospitalizations related to medication problems.Conclusion:The incidence of hospitalizations associated with medication problems in people with dementia increased between 2010 and 2019.

Stealth Liposomal Chemotherapeutic Agent for Triple Negative Breast Cancer with Improved Pharmacokinetics.

Triple-negative breast cancer is one of the most lethal cancers. Chemotherapeutics for targeting CDK4 and CDK6 like Palbociclib (PAB) in triple-negative breast cancer was widely explored. However, poor bioavailability and severe side effects profile limiting its clinical usage in the field of cancer chemotherapy. Herein, we set out to develop the stealth liposomes (LPS) of PAB by rotary thin film evaporation with a vesicle size of less than 100 nm. In vitro, drug release studies were performed and fitted into different release kinetic models. LPS were characterized by electron microscopic techniques for morphology. The engineered nanotherapeutics agents were further evaluated in 4T1 triple-negative breast cancer cell lines for its anti-cancer potential and cellular uptake. The hemolytic potential and pharmacokinetic (PK) behavior of developed LPS-PAB and PAB were analyzed by using robust UHPLC-QTOF-MS method. LPS-PAB demonstrates biphasic release profile with first-order release kinetics. Further, LPS-PAB has shown less IC50 value (1.99 µM) compared to PAB alone (3.24 µM). The designed nanoliposomes were tagged with fluorescent FITC dye to check rapid cellular uptake. Importantly, stealth LPS-PAB has shown a 1.75-fold reduction in hemolytic potential as compared to PAB plain drug at 100 µg/mL concentration. The PK results obtained was displayed 2.5-fold increase in Cmax, 1.45-fold increase in AUCtot, 1.8-fold increase in half-life and 1.3-fold increase in MRT with LPS-PAB when compared to orally administered PAB suspension. These findings suggest that novel LPS-PAB can be employed as an alternate therapeutic strategy to eradicate triple-negative breast cancer.

Vitamin E Oil Incorporated Liposomal Melphalan and Simvastatin: Approach to Obtain Improved Physicochemical Characteristics of Hydrolysable Melphalan and Anticancer Activity in Combination with Simvastatin Against Multiple Myeloma.

The objective of this research was to develop vitamin E oil (VEO)-loaded liposomes for intravenous delivery and to study the VEO effect on melphalan (MLN) loading, release, and stability. Further, the research aim was to determine the in vitro anticancer activity and in vivo systemic toxicity of MLN and simvastatin (SVN) combinations, for repurposing SVN in multiple myeloma. The liposomes were prepared by thin-film hydration technique. The optimized liposomes were surface modified with Pluronic F108, lyophilized, and evaluated for mean particle size, MLN content and release behavior, and in vitro hemolysis, cytotoxicity, and macrophage uptake characteristics. Further, in vivo acute toxicity of plain MLN + SVN combination was determined in comparison to their liposomal combination. The VEO alone and in combination with D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) has significantly increased the MLN and SVN loading. The reconstituted liposomes showed the mean particle size below 200nm (cryo-transmission electron microscope analysis also revealed the liposome formation). In presence of VEO, the liposomes have shown substantially controlled drug release, lower hemolysis, sustained cytotoxicity, lower phagocytosis, and moderately improved chemical stability. Besides, the effect of liposomal combination on mice bodyweight is found substantially lower than the plain drug combination. In conclusion, the VEO could be used along with phospholipids and cholesterol to develop liposomal drugs with improved physicochemical characteristics. Further, the interesting cytotoxicity study results indicated that SVN could be repurposed in combination with anticancer drug MLN against multiple myeloma; liposomal drugs could be preferred to obtain improved efficacy with decreased systemic toxicity.

Development of Chitosan–Tripolyphosphate Nanoparticles as Glycopeptide Antibiotic Reservoirs and Ex vivo Evaluation for Their Potential to Enhance the Corneal Permeation in Ocular Drug Delivery

Purpose: The present investigation aimed to prepare Vancomycin-loaded nanoparticles (VAN-NPs) using chitosan (CS) and tripolyphosphate (TPP) besides exploring the effects of changing CS/TPP ratio on the physicochemical properties, corneal permeation, and ocular delivery of the prepared NPs. Methods: Different pre-formulations were prepared using the modified ionic gelation process, then were characterized in terms of size distribution. Optimized formulations were furtherly evaluated by some characteristic tools such as Fourier-transform infrared (FTIR) spectroscopy and thermogravimetric analysis (TGA). The in vitro antimicrobial efficacy and drug release amounts along with the Ex-vivo corneal permeation of NPs through the sheep cornea were investigated. Quantification was performed using High-Performance Liquid Chromatography. Results: Spherical and uniformly distributed NPs were developed with a mean particle size varied between 215–290 nm. FTIR spectroscopy confirmed that the CS/TPP cross-linking has taken place without affecting the pharmacologically active moiety of the drug. The obtained zeta potential values were in the range of +34 to +37 mV, which could ensure the stability of formulations. TGA analysis indicated enhanced thermal stability for the encapsulated drug compared to the plain drug. Formulations indicated suitable antimicrobial efficacy while releasing more than 90% of the drug during 24 h. NPs offered a 10-fold enhancement in corneal permeation compared to the drug solution. Conclusions: Although further in vivo evaluation is still required to completely confirm the efficacy of the formulations, the enhanced release and corneal permeation of the drug suggest that the prepared NPs are suitable for ocular delivery of VAN.

Role of solid lipid nanoparticles as drug delivery vehicles on the pharmacokinetic variability of Erlotinib HCl

Background and objectivesErlotinib HCl is approved for the treatment of metastatic non-small cell lung cancer. Owing to its poor aqueous solubility and presystemic metabolism, Erlotinib HCl has poor oral bioavailability. Presence of food shows the variability in pharmacokinetics of erlotinib especially in absorption. The present study is aimed at developing solid lipid nanoparticles for Erlotinib HCl and evaluate their role on the bioavailability and food dependent variability in its absorption. MethodsSolid lipid nano particles were formulated by rota evaporation melt method and characterized by zeta sizer, FT-IR spectroscopy, X-ray diffraction and differential scanning calorimetry and In vivo pharmacokinetic studies in SD rats. A sensitive and specific high-performance liquid chromatography method was developed for the determination drug concentration in rat's plasma. The pharmacokinetic data was analysed using phoenix 32 WinNonlin software. ResultsThe average particle size and zeta potential of the optimized Erlotinib SLN was found to be 177 nm and −33 mV. All the characterization studies indicated there were no interactions between drug and excipients and the drug is inside the nanoparticles. Linearity was observed for the Erlotinib HCl in rat's plasma from 5 to 30 μg/mL. In vivo pharmacokinetics study in rat model showed significant increase in the oral bioavailability (2.12-fold) and reduced variability in area under the curve (from 2.5 to 1.4) from fed to fasted state using solid lipid nanoparticles over the plain drug. ConclusionSolid lipid nanoparticles showed significant improvement in bioavailability along with reduction in pharmacokinetic variability.

Nanoparticle-eluting stents for coronary intervention: formulation, characterization, and in vitro evaluation.

Coronary artery disease (CAD) is currently a leading cause of death worldwide. In the history of percutaneous coronary intervention for the treatment of CAD, a drug-eluting stent (DES) is recognized as a revolutionary technology that has the unique ability to significantly reduce restenosis and provide both mechanical and biological solutions simultaneously to the target lesion. The aim of the research work was to design and fabricate DES coated with a nanoparticulate drug formulation. Sirolimus, an inhibitor of the smooth muscle cell (SMC) proliferation and migration, was encapsulated in polymeric nanoparticles (NPs). The NP formulation was characterized for various physicochemical parameters. Cell viability and cell uptake studies were performed using human coronary artery smooth muscle cells (HCASMCs). The developed NP formulation showed enhanced efficacy compared to plain drug solution and exhibited time-dependent uptake into the HCASMCs. The developed NP formulation was coated on the Flexinnium™ ultra-thin cobalt-chromium alloy coronary stent platform. The NP-coated stents were characterized for morphology and residual solvent analysis. In vitro drug release was also evaluated. Ex vivo arterial permeation was carried out to evaluate the NP uptake from the surface of the stents. The characterization studies together corroborated that the developed NP coated stent can be a promising replacement of the current DESs.

Investigation on Potential of Chitosan Nanoparticles for Oral Bioavailability Enhancement of Risedronate Sodium.

Risedronate sodium (RS) is used in osteoporosis for bone reabsorption. It is a BCS class III drug having poor oral bioavailability (<0.63%) due to low permeability. In the present study, RS-loaded chitosan nanoparticles were developed to increase oral bioavailability and evaluated for various parameters. The DSC study indicated compatibility of RS with excipients in their physical mixture. The nanoparticles were prepared by ionotropic gelation technique and lyophilized. The optimized batch (RS-CNs) was found to have particles of size 268.7 nm and zeta potential of 24.9 mV. The TEM image of RS-CNs revealed discrete spherical particles. Angle of repose of 27.02 indicates good flow property of nanoparticles. FT-IR spectra of RS-CNs showed characteristic peaks of RS indicating compatibility of RS with the excipients. The mucin binding efficiency of RS-CNs was obtained as 63.42%. The in vitro release study of RS indicated controlled delivery from RS-CNs over 22 h. The release mechanism was found to be diffusion- and erosion-controlled release. Ex vivo study using rat intestine revealed faster permeation of 32.78% in 6 h from RS-CNs compared to plain drug solution. In vivo pharmacokinetic study in rats showed increased Cmax (1.8 fold) from RS-CNs compared to marketed formulation. The relative bioavailability of 193% from RS-CNs indicated significant enhancement in bioavailability upon nanoparticle formulation. The RS-CNs were found to be stable at room and refrigerated conditions. In conclusion, developed RS-loaded chitosan nanoparticles seem to be a promising approach to increase oral bioavailability and can avoid upper GI tract side effects.

Full Factorial Design for Development and Validation of a Stability-Indicating RP-HPLC Method for the Estimation of Timolol Maleate in Surfactant-Based Elastic Nano-Vesicular Systems.

A novel isocratic stability-indicating chromatographic method was developed, optimized and validated using Design-Expert® following ICH guidelines for the quantification of Timolol maleate (TM). The intrinsic stability of TM was assessed by force degradation studies, which concluded no extensive degradation except under alkaline and oxidative conditions. TM was quantified accurately in the surfactant-based elastic vesicular system by separating it on Hypersil BDS C8 column using triethylamine in H2O (0.15%v/v; pH3.0) and acetonitrile (ACN; 65:35%v/v). The influence of variable factors like mobile phase pH, injection volume (μL), flow rate (mL/min) and ACN content (%) on method responses were assessed using a full factorial design. The method was linear between 0.05 and 10μg/mL with an R2 value of 0.9993. Limit of detection and limit of quantification were found to be 0.90 and 27.2ng/mL. The method was specific, with recovery in plain drug solution of 89-92% and elastic nanovesicles of 90-93%. The experimental model was significant (P < 0.0001) as indicated by deliberate changes in the method analyzed through analysis of variance. The total drug content in elastic nanovesicles was estimated to be 9.53 ± 0.01mg/20-mL dispersion and entrapment efficiency was 44.52 ± 0.73%. The developed method was rapid, economic and precise for the quantification of TM in bulk and vesicular system.

Dual loaded nanostructured lipid carrier of nano-selenium and Etravirine as a potential anti-HIV therapy

There is a dire need for dual-long-acting therapy that could simultaneously target different stages of the HIV life cycle and providing a dual-prolonged strategy for improved anti-HIV therapy while reducing oxidative stress associated with the prolonged treatment. Thus, in the present work, nanostructured lipid carriers of Etravirine were developed and modified with nano-selenium. The dual-loaded nanocarrier system was fabricated using the double emulsion solvent evaporation method, further screened and optimized using the design of experiments methodology. The spherical core-shell type of a system was confirmed with an electron microscope and small-angle neutron scattering, while XPS confirmed the presence of selenium at the core-shell of the nanocarrier. In vitro assessment against HIV1 (R5 and X4 strains) infected TZM-bl cells exhibited higher efficacy for the dual-loaded nanocarrier system than the plain drug, which could be attributed to the synergistic effect of the nano-selenium. Confocal microscopy and flow cytometry results exhibited enhanced uptake in TZM-bl cells compared to plain drug. A significant increase of GSH, SOD, CAT was observed in animals administered with the dual-loaded nanocarrier system containing nano-selenium, suggesting the protective potential of the lipidic nanoparticle containing the nano-selenium. Improvement in the in vivo pharmacokinetic parameters was also observed, along with a higher accumulation of the dual-loaded nanocarrier in remote HIV reservoir organs like the brain, ovary, and lymph node. The results suggest the potential of a dual-loaded formulation for synergistically targeting the HIV1 infection while simultaneously improving the intracellular anti-oxidant balance for improving a prolonged anti-HIV therapy.