Low Bioavailable Drug Research Articles

Injectable nanogels to improve triamcinolone acetonide delivery and toxicity on the treatment of eye diseases.

Triamcinolone acetonide (TA) is a corticosteroid, and widely used in the treatment of eye diseases such as macular edema, proliferative vitreoretinopathy, and chronic uveitis. It's also used in diseases such as osteoarthritis and rheumatoid arthritis. Despite the width of its usage, it has toxicity in the eye. Nanogels are advantageous in applying toxic and low bioavailability drugs thanks to their swelling ability and stability. In the presented study, to minimize the disadvantages of TA, and to reach the drug into the back segment of the eye, TA-loaded chitosan (CS) nanogel (CS-TA Nanogel) has been prepared, and in vitro characterized. CS-TA nanogels were prepared by ionic gelation and characterized by SEM, FTIR, and TGA. Drug release profile, and in vitro cytotoxicity was determined to evaluate the efficacy of nanogels for intravitreal eye applications. DNA damage, and oxidative stress caused by nanogels in eye endothelial cells were investigated. CS and CS-TA nanogels were synthesized in the sizes range 200-300nm with an overall positive charge surface. The loading efficiency of TA on nanogels was determined as 50%. Cells exposed to 250µg/ml free TA showed 74% viability, while this rate was 90% in cells exposed to CS-TA nanogels. 8-OHdG levels were determined as 54.93 ± 1.118ng/mL in control cells and 92.47 ± 0.852ng/mL in cells exposed to 250µg/ml TA. TA both induces oxidative stress and causes DNA damage in HRMEC cells. However, administration of TA with carrier increased cell viability, total antioxidant capacity, and reduced oxidative DNA damage.

Characterization and in vitro evaluation of melanin nanoparticles as an oral drug delivery system: Studies using Caco-2 cell model and molecular dynamics simulations

Interest has been shown in the use of melanin nanoparticles (MNPs) for drug delivery applications. This study investigates the potential use of MNPs as an oral drug delivery system. The toxicity and cellular uptake of MNPs via intestinal barrier were evaluated using the Caco-2 cell model. Doxorubicin (DOX) was selected as a representative low bioavailability drug. The DOX-release profile of drug-loaded MNPs and molecular dynamic (MD) simulation were investigated at different pH. Our results demonstrated that MNPs synthesized from dopamine HCl are suitable as nanocarriers, presenting as monodisperse particles at mean size <300 nm. MNPs at size 89, 156, 268 nm at 3.13–50 μg/mL showed a high biocompatibiltity with Caco-2 cells, since no significant changes in %cell viability, reactive oxygen species, mitochondria membrane potential, and inflammatory cytokine were observed. The TEM results exhibited cellular internalization of MNPs into Caco-2 cells. The loading capacity (LC) and entrapment efficiency (EE) of DOX-loaded MNPs were 13.3 ± 2.7 % and 30.0 ± 3.6 %, respectively. DOX-loaded MNPs possessed a pH-dependent drug release profile. At pH 1.2, the amount of liberated DOX was 1.6- and 3.8-fold increase in comparison to pH 5 and 7.4, respectively. MD simulation clearly demonstrated that the binding affinity between polydopamines of MNPs and DOX molecules was weaker at the lower pH. These results thus support the potential use of MNPs as an oral drug delivery system particularly for drugs used in cancer treatment.

Applications of Nanotechnology-mediated Herbal Nanosystems for Ophthalmic Drug.

In recent years, herbal nanomedicines have gained tremendous popularity for novel drug discovery. Nanotechnology has provided several advances in the healthcare sector, emerging several novel nanocarriers that potentiate the bioavailability and therapeutic efficacy of the herbal drug. The recent advances in nanotechnology with accelerated strategies of ophthalmic nanosystems have paved a new path for overcoming the limitations associated with ocular drug delivery systems, such as low bioavailability, poor absorption, stability, and precorneal drug loss. Ophthalmic drug delivery is challenging due to anatomical and physiological barriers. Due to the presence of these barriers, the herbal drug entry into the eyes can be affected when administered by following multiple routes, i.e., topical, injectables, or systemic. However, the advancement of nanotechnology with intelligent systems enables the herbal active constituent to successfully entrap within the system, which is usually difficult to reach employing conventional herbal formulations. Herbal-loaded nanocarrier drug delivery systems demonstrated enhanced herbal drug permeation and prolonged herbal drug delivery. In this current manuscript, an extensive search is conducted for original research papers using databases Viz., PubMed, Google Scholar, Science Direct, Web of Science, etc. Further painstaking efforts are made to compile and update the novel herbal nanocarriers such as liposomes, polymeric nanoparticles, solid lipid nanoparticles, nanostructure lipid carriers, micelles, niosomes, nanoemulsions, dendrimers, etc., which are mostly used for ophthalmic drug delivery system. This article presents a comprehensive survey of diverse applications used for the preventative measures and treatment therapy of varied eye disorders. Further, this article highlights the recent findings that the innovators are exclusively working on ophthalmic nanosystems for herbal drug delivery systems. The nanocarriers are promising drug delivery systems that enable an effective and supreme therapeutic potential circumventing the limitations associated with conventional ocular drug delivery systems. The nanotechnology-based approach is useful to encapsulate the herbal bioactive and prevent them from degradation and therefore providing them for controlled and sustained release with enhanced herbal drug permeation. Extensive research is still being carried out in the field of herbal nanotechnology to design an ophthalmic nanosystem with improved biopharmaceutical properties.

Nanosponges: A Targeted Drug Delivery System

The latest advances in nanotechnology have resulted in the development of a targeted drug delivery system. However, in order to efficiently target a molecule to a specific place with a drug delivery system, a specialized drug delivery system is required. The discovery of nanosponge has been a big step toward overcoming challenges such as drug toxicity, low bioavailability, and predictable drug release because they can accept both hydrophilic and hydrophobic drugs. Nanosponges, a newly developed colloidal system, have the potential to address concerns such as medicine toxicity, lower bioavailability, and drug release over a large region because they can be adjusted to operate with both hydrophilic and hydrophobic pharmaceuticals. Nanosponges are small structures with a three-dimensional network and porous hollow. Nanosponges are small structures with a three-dimensional network and porous hollow. They can be easily created by crosslinking cyclodextrins with various chemicals. Because of Cyclodextrin's excellent biocompatibility, stability, and safety, a number of Cyclodextrin-based drug delivery systems have been rapidly developed. The nanosponge drug delivery system has a wide range of applications, including cancer, autoimmune illnesses, theranostic uses, increased bioavailability, and stability. This review delves into the benefits and downsides, preparation procedures, factors influencing their preparation, characterisation techniques, applications, and the most recent advancements in nanosponges. Nanosponges can also act as an efficient carrier of enzymes, proteins, vaccines, and antibodies. The current review focuses on the method of preparation, characterisation, and possible application in drug delivery systems.

P‐toluenesulfonychloride‐based niosomes for Amphotericin‐B against Leishmaniasis

AbstractNonionic‐surfactants have been reported as nanocarriers for delivering low bioavailable drugs at the target sites. In the current study, two new nonionic surfactants were synthesized to enhance the oral bioavailability of the low water‐soluble antifungal drug Amphotericin‐B. The hemolysis effect of nonionic surfactants on red blood cells and cytotoxicity against the 3T3 cell line was studied. Both surfactants have shown low hemolysis and cytotoxicity as compared to standard Tween 80. The morphology of drug‐loaded niosomes of nonionic surfactants 1 and 2 was studied by using atomic force microscopy (AFM), and both surfactants based vesicles were spherical, while their average sizes were measured by dynamic light scattering (DLS). The average size, zeta potential and polydispersity index (PDI) values of surfactants 1 and 2 were 282 ± 3 nm, −8 ± 1 mV, 0.26 and 287 ± 3 nm, −10 ± 1 mV, 0.24. The drug entrapment efficiency and critical micelle concentrations of nonionic surfactants were determined by using UV–visible spectroscopy. The structures of surfactants 1 and 2 were assessed through single‐crystal x‐ray crystallographic analysis, while Hirshfeld analysis was performed to study the intermolecular interactions of molecules, as well as the packing behavior of their crystals. The nonionic‐surfactant 1 was further tested for antileishmanial activity against Leishmania tropica promastigotes, in both drug‐loaded and unloaded niosomal vesicular forms. The nonionic surfactant 1 was found to be a potentanti‐leishmanial agent in the drug‐loaded form with IC50 = 3.02 ± 0.91 μM in comparison to their standard drugs Amphotericin‐B (IC50 = 3.8 ± 0.04 μM) and miltefosine (IC50 = 42.2 ± 0.6 μM) (p &lt; 0.1). These results, therefore, form the basis of further results towards efficient drug delivery against tropical disease Leishmaniasis.

DEVELOPMENT AND EVALUATION OF ITRACONAZOLE SOLID DISPERSION GEL CUTANEOUS DELIVERY

Objective: The objective of this research is to enhance the permeation of low bioavailable drugs with suitable dosage forms by utilizing various permeation enhancers. Methods: Solid dispersions (SDs) were prepared by kneading, whereas physical mixtures (PM) were prepared by simple mixing with polymers PEG 6000 and PEG 20000 and evaluated for various physicochemical parameters. Optimized SDs were converted to gels using a variety of polymers and were evaluated for in vitro and ex vivo permeation studies. Results: It was found that the percentage of drugs in SDs and PMs was within the limit. The dissolution of SDs and PMs was found to be the highest with PEG-6000 (99.78% within 240 min) compared to PEG 20000. The maximum drug release (92.9% within 8 h) was achieved with oleic acid in both in vitro and ex vivo permeation studies, as evidenced by the in vitro and ex vivo permeation studies. The developed formulations showed no incompatibility between drugs and excipients, as demonstrated by drug and excipient interaction studies. Conclusion: The results that were observed confirmed that the itraconazole PEG-6000 gel developed has promising effects on desirable skin permeation.

Saquinavir-Piperine Eutectic Mixture: Preparation, Characterization, and Dissolution Profile.

The dissolution rate of the anti-HIV drug saquinavir base (SQV), a poorly water-soluble and extremely low absolute bioavailability drug, was improved through a eutectic mixture formation approach. A screening based on a liquid-assisted grinding technique was performed using a 1:1 molar ratio of the drug and the coformers sodium saccharinate, theobromine, nicotinic acid, nicotinamide, vanillin, vanillic acid, and piperine (PIP), followed by differential scanning calorimetry (DSC). Given that SQV-PIP was the only resulting eutectic system from the screening, both the binary phase and the Tammann diagrams were adapted to this system using DSC data of mixtures prepared from 0.1 to 1.0 molar ratios in order to determine the exact eutectic composition. The SQV-PIP system formed a eutectic at a composition of 0.6 and 0.40, respectively. Then, a solid-state characterization through DSC, powder X-ray diffraction (PXRD), including small-angle X-ray scattering (SAXS) measurements to explore the small-angle region in detail, Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and a powder dissolution test were performed. The conventional PXRD analyses suggested that the eutectic mixture did not exhibit structural changes; however, the small-angle region explored through the SAXS instrument revealed a change in the crystal structure of one of their components. FT-IR spectra showed no molecular interaction in the solid state. Finally, the dissolution profile of SQV in the eutectic mixture was different from the dissolution of pure SQV. After 45 min, approximately 55% of the drug in the eutectic mixture was dissolved, while, for pure SQV, 42% dissolved within this time. Hence, this study concludes that the dissolution rate of SQV can be effectively improved through the approach of using PIP as a coformer.

A model-based pharmacokinetic assessment of drug–drug interaction between tacrolimus and nirmatrelvir/ritonavir in a kidney transplant patient with COVID-19

We experienced a patient with a remarkable and prolonged increase in tacrolimus blood concentrations when nirmatrelvir/ritonavir was concomitantly used. The inhibitory intensity and duration of nirmatrelvir/ritonavir on tacrolimus pharmacokinetics were examined using a model-based analysis. A renal transplant patient taking oral tacrolimus continuously was treated with nirmatrelvir/ritonavir for 5 days. The baseline tacrolimus trough blood concentration was 4.2 ng/mL. Tacrolimus was discontinued on Day 6 after the concomitant administration of nirmatrelvir/ritonavir, and the trough concentration increased to 96.4 ng/mL on Day 7. The model-based analysis showed that tacrolimus clearance decreased to 35% and bioavailability increased by 18.7-fold after the coadministration of nirmatrelvir/ritonavir, compared with before the coadministration. Therefore, nirmatrelvir/ritonavir drastically decreased both the apparent clearance and apparent volume of distribution. Simulated tacrolimus concentrations could be best fitted to the observed concentrations when the inhibitory effects of nirmatrelvir/ritonavir were modeled to disappear over about 10 days by first-order elimination. In conclusion, nirmatrelvir/ritonavir greatly increases tacrolimus concentrations by not only reducing clearance, but also increasing bioavailability. Interactions between nirmatrelvir/ritonavir and low-bioavailability drugs which are substrates for CYP3A and P-glycoprotein, such as tacrolimus, are harmful, and concomitant use of these medicines should be avoided.

Mitigation of pesticide-mediated ocular toxicity via nanotechnology-based contact lenses: a review.

Thexenobioticstress exerted by pesticides leads to the deterioration of human and animal health including ocular health. Acute or prolonged exposure to these agricultural toxicants has been implicated in a number of pathological conditions of the eye such as irritation, epiphora or hyper-lacrimation, abrasions on the ocular surface, and decreased visual acuity. The issue is compounded by the fact that tissues of the eye absorb pesticides faster than other organs of the body and are more susceptible to damage as well. However, there is alacunain our knowledge regarding the ways by which pesticide exposure-mediated ocular insult might be counteracted. Topical instillation of drugs known to combat the pesticide induced toxicity has been explored to mitigate the detrimental impact of pesticide exposure. However, topical eye drop solutions exhibit very low bioavailability and limited drug residence duration in the tear film decreasing their efficacy. Contact lenses have been explored in this respect to increase bioavailability of ocular drugs, while nanoparticles have lately been utilized to increase drug bioavailability and increase drug residence duration in different tissues. The current review focuses on drug delivery and futuristic aspects of corneal protection from ocular toxicity using contact lenses.

Refinement of safety and efficacy of anti-cancer chemotherapeutics by tailoring their site-specific intracellular bioavailability through transporter modulation.

Low intracellular bioavailability, off-site toxicities, and multi drug resistance (MDR) are the major constraints involved in cancer chemotherapy. Many anticancer molecules fail to become a good lead in drug discovery because of their poor site-specific bioavailability. Concentration of a molecule at target sites is largely varied because of the wavering expression of transporters. Recent anticancer drug discovery strategies are paying high attention to enhance target site bioavailability by modulating drug transporters. The level of genetic expression of transporters is an important determinant to understand their ability to facilitate drug transport across the cellular membrane. Solid carrier (SLC) transporters are the major influx transporters involved in the transportation of most anti-cancer drugs. In contrast, ATP-binding cassette (ABC) superfamily is the most studied class of efflux transporters concerning cancer and is significantly involved in efflux of chemotherapeutics resulting in MDR. Balancing SLC and ABC transporters is essential to avoid therapeutic failure and minimize MDR in chemotherapy. Unfortunately, comprehensive literature on the possible approaches of tailoring site-specific bioavailability of anticancer drugs through transporter modulation is not available till date. This review critically discussed the role of different specific transporter proteins in deciding the intracellular bioavailability of anticancer molecules. Different strategies for reversal of MDR in chemotherapy by incorporation of chemosensitizers have been proposed in this review. Targeted strategies for administration of the chemotherapeutics to the intracellular site of action through clinically relevant transporters employing newer nanotechnology-based formulation platforms have been explained. The discussion embedded in this review is timely considering the current need of addressing the ambiguity observed in pharmacokinetic and clinical outcomes of the chemotherapeutics in anti-cancer treatment regimens.

Therapeutic applications of contact lens-based drug delivery systems in ophthalmic diseases

Traditional ophthalmic drugs, such as eye drops, gels and ointments, are accompanied by many problems, including low bioavailability and potential drug side effects. Innovative ophthalmic drug delivery systems have been proposed to overcome the limitations associated with traditional formulations. Recently, contact lens-based drug delivery systems have gained popularity owing to their advantages of sustained drug delivery, prolonged drug retention, improved bioavailability, and few drug side effects. Various methods have been successfully applied to drug-loaded contact lenses and prolonged the drug release time, such as chemical crosslinking, material embedding, molecular imprinting, colloidal nanoparticles, vitamin E modification, drug polymer film/coating, ion ligand polymerization systems, and supercritical fluid technology. Contact lens-based drug delivery systems play an important role in the treatment of multifarious ophthalmic diseases. This review discusses the latest developments in drug-loaded contact lenses for the treatment of ophthalmic diseases, including preparation methods, application in ophthalmic diseases and future prospects.

Hyperbranched Copolymers of Methacrylic Acid and Lauryl Methacrylate H-P(MAA-co-LMA): Synthetic Aspects and Interactions with Biorelevant Compounds.

The synthesis of novel copolymers using one-step reversible addition-fragmentation chain transfer (RAFT) copolymerization of biocompatible methacrylic acid (MAA), lauryl methacrylate (LMA), and difunctional ethylene glycol dimethacrylate (EGDMA) as a branching agent is reported. The obtained amphiphilic hyperbranched H-P(MAA-co-LMA) copolymers are molecularly characterized by size exclusion chromatography (SEC), FTIR, and 1H-NMR spectroscopy, and subsequently investigated in terms of their self-assembly behavior in aqueous media. The formation of nanoaggregates of varying size, mass, and homogeneity, depending on the copolymer composition and solution conditions such as concentration or pH variation, is demonstrated by light scattering and spectroscopic techniques. Furthermore, drug encapsulation properties are studied by incorporating the low bioavailability drug, curcumin, in the nano-aggregate hydrophobic domains, which can also act as a bioimaging agent. The interaction of polyelectrolyte MAA units with model proteins is described to examine protein complexation capacity relevant to enzyme immobilization strategies, as well as explore copolymer self-assembly in simulated physiological media. The results confirm that these copolymer nanosystems could provide competent biocarriers for imaging and drug or protein delivery/enzyme immobilization applications.

Nanosponges: A Novel Class of Versatile Drug Delivery System – Review

Nanotechnology advancements have resulted in the creation of tailored medicine delivery systems. However, properly targeting a molecule to a specific region with a drug delivery system necessitates using a specialized drug delivery system. The development of nanosponge has become a crucial step in solving some challenges such as drug toxicity, low bioavailability, and predictable drug release. Many drug delivery methods, such as nanoparticles, nanoemulsions, nanosuspensions, and nanosponges, have been developed via nanomedicine technology. Nanosponges are little sponges like the size of a virus that may be loaded with a vast range of medications. Nanosponges serve an essential function in regulated medication delivery. These mini sponges may flow throughout the human body until they reach the same target region. They adhere to the surface and begin to release the medicine in a regulated and predictable way. The outside surface is often porous, which allows for regulated medication release. The important feature of these sponges is their aqueous solubility, which makes them appropriate for medications with low solubility. Their molecular architecture is often composed of several polymer chains that can generate unique microdomains suited for co-encapsulating two medicines with different chemical structures. When used to release insoluble medications, nanosponges also shield the active components from physicochemical deterioration. Nanosponges can be made into a number of dosage forms, including parenteral, aerosol, tablets, topical, and capsules, thanks to their small size and spherical structure. This study focuses on the techniques of synthesis and applications of nanosponges in the realm of medication delivery.

Research Progress in the Field of Gambogic Acid and Its Derivatives as Antineoplastic Drugs.

Gambogic acid (GA) is a natural product with a wide range of pharmacological properties. It plays an important role in inhibiting tumor growth. A large number of GA derivatives have been designed and prepared to improve its shortcomings, such as poor water solubility, low bioavailability, poor stability, and adverse drug effects. So far, GA has been utilized to develop a variety of active derivatives with improved water solubility and bioavailability through structural modification. This article summarized the progress in pharmaceutical chemistry of GA derivatives to provide a reference and basis for further study on structural modifications of GA and expansion of its clinical applications.

A Detailed Review on Fast Dissolving Niosomal Films for Sublingual Drug Delivery

Fast dissolving or Quick-dissolving dosage forms have great importance in the pharmaceutical field due to their special properties and advantages. Fast-dissolving dosage forms breakdown immediately in the salivary fluids of the oral cavity within a minute, where they release the active pharmaceutical ingredient. Sublingual drug delivery system is a novel route of drug administration in which the drug substance is placed under the tongue and is directly absorbed via the blood vessels and produces the immediate onset of action. Noisome are closed bilayer vesicles formed by self-assembly of nonionic surfactant in an aqueous medium. Noisome is similar to liposome but has the ability to increase the stability of the drug. Formulated niosomes are added into the film-forming polymers to obtain sublingual niosomal films. Fast dissolving niosomal film is suitable for the drugs which show high first-pass metabolism or hepatic metabolism, low bioavailability drugs, and have a short half-life drugs. Fast Dissolving Niosomal Films used to improve the oral bioavailability and reduce the dose and dosing frequency, which reduce systemic side effects and as well as cost-effective. Niosomes allow the prolonged release of the drug and film was used to increase the bioavailability of drugs via the sublingual route of drug administration. Fast dissolving niosomal films have great importance during emergency conditions like allergy, short-term spasm, and asthma whenever an immediate onset of action is required. Fast dissolving films are also suitable for pediatric, geriatric, and dysphasic patients or patients with fear of choking.

Ocular microemulsion of brinzolamide: Formulation, physicochemical characterization, and in vitro irritation studies based on EpiOcular™ eye irritation assay

In recent years, the hydrophobic active substances have led researchers to develop new formulations to enhance bioavailability and dissolution rate; brinzolamide, a lipophilic drug belongs to carbonic anhydrase inhibitors, which cause reduction of intraocular pressure in patients suffering from glaucoma. Currently, the marketed product of brinzolamide is in the form of ocular drops; nonetheless, the conventional drops provide decreased therapeutic efficacy owing to their low bioavailability and pulsed drug release. Thus, the development of novel ocular formulations such as topical microemulsions is of high importance. In this work, the preparation of new microemulsions containing brinzolamide (0.2, 0.5 and 1% w/w) and comprised from isopropyl myristate, tween 80 and span 20 and Cremophor EL was performed. The obtained microemulsions were further characterized for their physicochemical properties. In addition, Fourier Transformed-Infrared spectroscopy was used touate the compatibility of active ingredients and components. In vitro release studies along with kinetic modeling were performed using the dialysis membrane method in simulated tear fluid. Bioadhesion studies were performed using Texture analysis. Finally, in vitro ocular irritation based on EpiOcular™ Eye Irritation Test and cytocompatibility studies was performed to examine any possible harm on ocular cells and predict in vivo safety profile.

Preparation of astaxanthin micelles self-assembled by a mechanochemical method from hydroxypropyl β-cyclodextrin and glyceryl monostearate with enhanced antioxidant activity

This research aimed to overcome the current challenges in the application of natural carotenoid antioxidants, such as their complex preparation processes, low bioavailability and poor drug stability. Herein, a mechanochemical method was used to prepare an inclusion complex (IC) that self-assembles into micelles in aqueous solution and achieves solid-phase loading of astaxanthin (AST). The NMR analysis, thermodynamics study, particle size analysis and electron microscopy image results showed that AST, hydroxypropyl β-cyclodextrin (HPβ-CD) and glyceryl monostearate (GMS) formed self-assembled micelles and maintained good stability in aqueous solution. The antioxidant performance experiments showed that the formation of IC increases free radical scavenging activity. The pharmacokinetic studies showed that the bioavailability of the astaxanthin inclusion complex increased 4-fold. The tissue distribution experiments showed that the astaxanthin inclusion complex targets the liver to exert its antioxidant effects. The proposed method uses an innovative preparation technology to produce an efficient drug delivery system without solvents, and it exerts powerful antioxidant activity against astaxanthin.

Natural products for treatment of Plasmodium falciparum malaria: An integrated computational approach

Malaria is a life-threatening infectious disease with an estimated 229 million cases in the year 2019 worldwide. Plasmodium falciparum 1-deoxy-d-xylulose-5-phosphate reductoisomerase (PfDXR) is one of the key enzymes in the biosynthetic pathway of isoprenoid, (required for parasite growth and survival) and considered as an attractive target for designing anti-malarial drugs. Fosmidomycin is an effective DXR inhibitor and has been proven effective and safe against P. falciparum in clinical trials. However, due to low bioavailability and inappropriate drug attributes, it is not a preferred option. The present study was performed to identify PfDXR inhibitors with improved pharmacology/safety. For this purpose, an integrated computational framework, comprising of pharmacophore modeling, virtual screening, molecular docking, molecular dynamics (MD) simulation and MM/PBSA, was used. The binding free energy analysis was performed using a focused library of phytochemicals established from medicinal plants. The study identified four bioactive compounds namely, Myricetin 3-rhamnoside, 7-O-Galloyltricetiflavan, (25S)-5-beta-spirostan-3-beta-ol 3-O-beta-d-glucopyranosyl-(1->2)-beta-d-glucopyranoside, and Oleanolic acid 28-O-beta-d-glucopyranoside as potential inhibitors of PfDXR. The selection of these four compounds was based on pharmacophore mapping, docking score, binding stability, molecular interactions with the residues of PfDXR active site, binding stability and free energy estimation. In conclusion, medicinal plant-based scaffolds were predicted with enhanced efficacy and adequate physiochemical/pharmacokinetic profile that might be helpful in controlling malaria.

Optimization of Hydroxy Propyl Methyl Cellulose and Carbomer In Diltiazem Hydrochloride Mucoadhesive Buccal Film

Diltiazem hydrochloride (HCl) is a category of calcium channel blocker used as an antihypertensive agent. Diltiazem HCl is a low bioavailable drug due to high first-pass metabolism and a short half-life (3-5 hours); hence mucoadhesive buccal film was made to overcome this weakness. Bioavailability of Diltiazem HCl increase if the buccal preparations can contact the mucosa for a sufficient time. Therefore, in this study, two polymers are combined to obtain good film characteristics, especially residence time and mucoadhesive strength. This study was aimed to optimize Hydroxy Propyl Methyl Cellulose (HPMC) and Carbomer's amount in Diltiazem HCl mucoadhesive buccal film. The formulas were prepared by the solvent casting method and optimized with design expert software. The release kinetics and mechanism were evaluated using DDSolver program. The optimum amount of polymer obtained from optimization was 40 mg of HPMC and 10 mg of Carbomer. The optimum formula's swelling index was 4.18. The mucoadhesive strength was 53.07 gF, and the mucoadhesive residence time was 529.33 min. The FTIR spectra showed there was no interaction between Diltiazem HCl and other excipients. Thus it did not disturb the therapeutic effect. Based on the DDSolver statistical parameters and curve-fitting, the dissolution model of Diltiazem HCl from buccal mucoadhesive film follows Korsmeyer-Peppas. The release exponent (n) is 0.55, which shows a non-fickian/anomalous diffusion release mechanism. These mechanisms represent drug release controlled by a combination of diffusion and erosion.

Invivo Pharmacokientic and Pharamacodynamic Studies of Optimized Antihyperlipidemic Drug Loaded Solid Lipid Nanoparticle

The purpose of this research is to increase bioavailability by solid lipid nanoparticle (SLN) carrier for low bioavailable drugs (&lt; 5%) such as Lovastatin. Eight SLN loaded Lovastatin was designed and optimised by variables such as Particle Size (PS in nm) and Zeta Potential (ZP in mV) using a micro emulsification technique. SLN 7 was chosen as the optimised formulation according to the findings obtained and the same was chosen for invivo pharmacokinetic and triton-induced antihyperlipidemic operation. SLN7 confirms an improvement in bioavailability of 3.15 percent by an improvement in AUC compared to conventional dosage type (Altoprev) from the pharmacokinetic invivo results. SLN was also an appropriate career in drug delivery for Lovastatin by enhancing bioavailability and therapeutic response. The stability studies of SLN7 revealed that the evaluation parameters of SLN did not change significantly. It was verified from the data that the drug-loaded SLN was stable under varying temperature and humidity conditions. While compare to 25˚c±2˚c/ 60% RH, SLN are more stable in 4˚c±2˚c and shows good reproducible reports in Particle Size (nm), Zeta potential (mV), PI and EE% data. Therefore, Solid Lipid Nanoparticle is a viable drug carrier mechanism for low bioavailable Lovastatin to improve their bioavailability through efficiently permeating them.