Pharmacokinetics of vitamin dosage forms: A complete overview.

Vitamins are crucial for sustaining life because they play an essential role in numerous physiological processes. Vitamin deficiencies can lead to a wide range of severe health issues. In this context, there is a need to administer vitamin supplements through appropriate routes, such as the oral route, to ensure effective treatment. Therefore, understanding the pharmacokinetics of vitamins provides critical insights into absorption, distribution, and metabolism, all of which are essential for achieving the desired pharmacological response. In this review paper, we present information on vitamin deficiencies and emphasize the significance of understanding vitamin pharmacokinetics for improved clinical research. The pharmacokinetics of several vitamins face various challenges, and thus, this work briefly outlines the current issues and their potential solutions. We also discuss the feasibility of enhanced nanocarrier-based pharmaceutical formulations for delivering vitamins. Recent studies have shown a preference for nanoformulations, which can address major limitations such as stability, solubility, absorption, and toxicity. Ultimately, the pharmacokinetics of pharmaceutical dosage forms containing vitamins can impede the treatment of diseases and disorders related to vitamin deficiency.

Polysaccharide-based hydrogels for drug delivery and wound management: a review.

INTRODUCTION: Polysaccharide-based hydrogels (PBHs) offer several advantages over their synthetic counterparts. Their natural origin contributes to their nontoxicity, high biocompatibility, and in vivo biodegradability. Their properties can be tuned finely to obtain hydrogels with desired mechanical, structural, and chemical properties. AREAS COVERED: Such versatile characteristics have potentiated the use of PBHs for the delivery of drugs, vaccines, protein and peptide therapeutics, genes, cells, probiotics, bacteriophages, and other therapeutic agents. Recent advances in hydrogel-based formulations such as nanogels, microgels, microneedles, hydrogel beads, nanocarrier-loaded hydrogels, and complexation hydrogels have enabled the precise delivery of a wide range of therapeutics. This review aims to give a holistic overview of hydrogels in the delivery of a variety of therapeutics through different routes. EXPERT OPINION: PBHs have been used to enable the oral delivery of vaccines and other biologicals, thereby allowing self-administration of life-saving vaccines during public health emergencies. There is a lack of commercialized wound dressings for the treatment of chronic wounds. PBH-based wound dressings, especially those based on chitosan and loaded with actives and growth factors, have the potential to help in the long-term treatment of such wounds. Recent developments in the 3D printing of hydrogels can enable the quick and large-scale production of drug-loaded hydrogels.

Antiviral activity of green tea and black tea polyphenols in prophylaxis and treatment of COVID-19: A review.

BACKGROUND: The rapid spread of novel coronavirus called SARS-CoV-2 or nCoV has caused countries all over the world to impose lockdowns and undertake stringent preventive measures. This new positive-sense single-stranded RNA strain of coronavirus spreads through droplets of saliva and nasal discharge. PURPOSE: US FDA has authorized the emergency use of Remdesivir looking at the increasing number of cases of COVID-19, however there is still no drug approved to treat COVID-19. An alternative way of treatment could be the use of naturally derived molecules with known antiviral properties. METHOD: We reviewed the antiviral activities of two polyphenols derived from tea, epigallocatechin-3-gallate (EGCG) from green tea and theaflavins from black tea. Both green tea and black tea polyphenols have been reported to exhibit antiviral activities against various viruses, especially positive-sense single-stranded RNA viruses. RESULTS: Recent studies have revealed the possible binding sites present on SARS-CoV-2 and studied their interactions with tea polyphenols. EGCG and theaflavins, especially theaflavin-3,3'-digallate (TF3) have shown a significant interaction with the receptors under consideration in this review. Some docking studies further emphasize on the activity of these polyphenols against COVID-19. CONCLUSION: This review summarizes the available reports and evidences which support the use of tea polyphenols as potential candidates in prophylaxis and treatment of COVID-19.

Docetaxel Loaded Pomegranate Seed Oil Based Nanostructured Lipid Carriers: A Potential Alternative to Current Formulation.

The current work is focused on the development of docetaxel loaded pomegranate seed oil based lipid nanosystem. Docetaxel loaded pomegranate seed oil nanostructured lipid carriers (DTX-PSO-NLCs) were formulated by the melt emulsification method for parenteral delivery. The developed formulation was characterized in terms of their physicochemical parameters, solid-state characterization, in vitro drug release, in vitro cytotoxicity studies, and in vivo pharmacokinetics and biodistribution studies. Stability studies were carried out as per ICH guidelines Q1A. Melt emulsification method resulted in the formulation of stable DTX-PSO-NLCs with a particle size in the range of 150-180 nm and an entrapment efficiency of 63-65%. The in vitro release showed a slow and sustained release of the drug from the formulation compared to the marketed formulation (i.e., Daxotel®). The formulation was found to be stable for a period of 12 months at conditions of 4°C ± 2°C, 25°C ± 2°C/60% RH ± 5%RH, and 40°C ± 2°C/75% RH ± 5%RH. The developed nanosystem exhibited promising antitumor activity against various types of cancerous cell lines (i.e., MCF7, DU145, U87MG, and NCI-H460) relative to the marketed formulation. The pharmacokinetic evaluation revealed that DTX-PSO-NLCs had a better kinetic profile compared to the marketed formulation. Graphical abstract.

Solid lipid nanoparticles of amphotericin B (AmbiOnp): in vitro and in vivo assessment towards safe and effective oral treatment module.

Amphotericin B, a gold standard broad spectrum antibiotic used in treatment of systemic fungal infections and visceral leishmaniasis, though is effective parenterally offers severe nephrotoxicity whereas the oral delivery is reported to give very meager oral bioavailability. Thus, to alleviate the toxicity and to improve oral bioavailability, an effective oral delivery approach in the form of solid lipid nanoparticles of amphotericin B (AmbiOnp) was reported earlier by our group. In this investigation, we report the predominant formation of nontoxic superaggregated form of amphotericin B, resulting from the probe sonication-assisted nanoprecipitation technique. The developed formulation was further confirmed to retain this nontoxic form and was found to be stable over the varied gastrointestinal conditions. Further, in vitro antifungal activity of AmbiOnp against Candida albicans showed minimum inhibitory concentration value of 7.812 µg/mL attributed to controlled release of drug from nanoparticulate matrix. In vivo pharmacokinetic studies revealed a relative bioavailability of AmbiOnp to be 1.05-fold with a Cmax of 1109.31 ± 104.79 ng/mL at the end of 24 h which was comparable to Cmax of 1417.49 ± 85.52 ng/mL achieved with that of marketed formulation (Fungizone®) given intravenously establishing efficacy of AmbiOnp. In vivo biodistribution studies indicated very low levels of Amphotericin B in kidneys when given as AmbiOnp as compared to that of marketed formulation proving its safety and was further corroborated by renal toxicity studies. Further, the formulations were found to be stable under refrigeration condition over a period of 3 months.

pH-sensitive nanoparticles of curcumin-celecoxib combination: evaluating drug synergy in ulcerative colitis model.

Inflammatory bowel diseases, which largely comprise ulcerative colitis (UC) and Crohn's disease, are increasingly posing as a global threat because of the incompetence of the current therapy in the entire patient population. This necessitates the identification of alternative therapeutic molecules or their combinations, which may serve as effective first-line or maintenance therapeutics. In this quest, celecoxib, a selective cyclooxygenase-2 inhibiting nonsteroidal anti-inflammatory agent and curcumin, a natural antioxidant and anti-inflammatory agent, have both been found to be useful in alleviating UC. Furthermore, studies involving their combination have proved synergistic action of these two agents. In the current investigation, we have formulated pH-sensitive nanoparticles of curcumin-celecoxib combination as a potential therapy for UC. Synergistic action of the drug combination, delivery advantages of nanosized carriers, and pH-sensitive nature of the polymer were collectively hypothesized to reduce the overall toxicity and total dose of celecoxib and provide enhanced efficacy for mitigating UC. The hypothesis was confirmed in a UC model in rats, where pH-sensitive nanoparticles of the drug combination were found to be more efficacious than nanoparticles of either drugs or drug/s suspension. Further, the blank nanoparticles did not exhibit any therapeutic effect, thereby confirming efficacy of the drug combination for treating UC.

Psoriasis clinical implications and treatment: a review.

Psoriasis is a common skin disorder affecting the population worldwide. It is a T-cell mediated autoimmune disorder leading to keratinocyte hyperproliferation. Psoriasis has genetic predisposition that is further aggravated by certain stimulating factors. In spite of significant advances in understanding the pathogenesis of psoriasis, the exact etiology of the disease remains unknown. The clinical manifestations of this disease include various forms that affect different parts of the body. Treatment options vary according to the mode of application or severity of the disease. Earlier treatments have included application of emollients or keratolytic agents to hydrate the skin or shed off the skin. But later treatments have been modified to treat the underlying T-cell proliferation. Hence, topical treatments like coal tar, vitamin D, retinoids, topical calcineurin inhibitors for treating mild psoriasis, systemic treatments including methotrexate, cyclosporine, acitretin, hydroxyurea, as well as light therapy for severe psoriasis have become more prominent. Current treatment modalities are associated with the risk of serious side effects from prolonged treatment. Combinations of these therapies have provided effective and rapid modalities to suppress the disease and reduce the side effects of treatment. In addition, newer carrier systems for conventional drugs are being developed to improve the effectiveness of treatment and reduce the side effects. Development of biologics and gene therapy have revolutionized the treatment of this skin disease. Although an array of therapies to suppress the psoriatic condition exists, none are curative.

Clotrimazole nanoemulsion for malaria chemotherapy. Part II: stability assessment, in vivo pharmacodynamic evaluations and toxicological studies.

The aim of present investigation was to evaluate the potential of clotrimazole as antimalarial drug. Due to poor aqueous solubility and high lipophilicity, it was previously formulated in a nanoemulsion based system. The intrinsic effects of nanoemulsion on improvement of antimalarial activity of clotrimazole were assessed in mice infected with Plasmodium berghei and compared to its suspension formulation. In four-day suppressive test, mice treated with 10mg/kg clotrimazole nanoemulsion showed the highest suppression of parasitemia and; parasitemia was significantly lower than that of 10mg/kg clotrimazole suspension. In onset of activity and recrudescence test, percent reduction of parasitemia was significantly higher in 10 and 15 mg/kg clotrimazole nanoemulsion groups compared to 15 mg/kg suspension group. In both murine models, survival of mice treated with nanoemulsion was significantly prolonged compared to suspension at equivalent doses. The inhibition of parasite growth by clotrimazole in the nanoemulsion was dose dependent as determined by test for linear trend. In repeated dose oral toxicity, levels of serum liver enzymes and biomarkers of hepatotoxicity did not vary significantly from control. Six-month stability testing of the clotrimazole nanoemulsion exhibited no changes in various physiochemical attributes of drug product compared to initial analysis.

Novel targets for malaria therapy.

Malaria has emerged as one of the most debilitating parasitic infection with about 500 million cases reported annually and one million deaths worldwide. Currently, Plasmodium falciparum has developed resistance to almost all classes of antimalarials, thus precluding the use of those agents which once formed the cornerstone of malaria therapy. In lieu of this phenomenon, and taking into consideration the absence of an effective vaccine for malaria, the only way to combat the deadly parasite is to enrich the antimalarial cache with new molecules acting on fresh targets in the parasite. After potential targets have been validated, these targets can be used as basis for screening compounds to identify new leads followed by lead optimization. This review discusses novel targets of the malaria parasite that can be utilized to treat the disease.

Curcumin-loaded hydrogel nanoparticles: application in anti-malarial therapy and toxicological evaluation.

The present investigation involved preparation of hydrogel nanoparticles using a combination of hydroxyl propyl methyl cellulose and polyvinyl pyrrolidone. The objective was to exploit the size and hydrophilic nature of the formulated nanocarriers to enhance absorption and prolong the rapid clearance of curcumin due to possible evasion of the reticulo-endothelial system. Reproducible nanoparticles of size around 100 nm, a fairly narrow distribution and encapsulation efficiency of 72%, were produced by the solvent emulsion-evaporation technique. This optimized system was further subjected to freeze-drying. The freeze-dried product was readily reconstituted with distilled water. The reconstituted product exhibited a size and distribution similar to that before freeze-drying, drug content of greater than 99% and presence of amorphous drug when analyzed by differential scanning calorimetry (DSC) which may result in possible improved absorption of curcumin. In vivo anti-malarial studies revealed significant superior action of nanoparticles over curcumin control suggesting the possibility of the formulation being employed as an adjunct anti-malarial therapy along with the standard therapy. Acute and subacute toxicity studies confirmed the oral safety of the formulation. A battery of genotoxicity studies was conducted to evaluate the nongenotoxic potential of the developed formulation thus indicating the possibility of the formulation being employed for prolonged duration.

Development and evaluation of lorazepam microemulsions for parenteral delivery.

The objective of this investigation was to develop lorazepam (LZM) microemulsions as an alternative to the conventional cosolvent based formulation. Solubility of LZM in various oils and Tween 80 was determined. The ternary diagram was plotted to identify area of microemulsion existence and a suitable composition was identified to achieve desired LZM concentration. The LZM microemulsions were evaluated for compatibility with parenteral fluids, globule size, in vitro hemolysis and stability of LZM. Capmul MCM demonstrated highest solubilizing potential for LZM and was used as an oily phase. LZM microemulsions were compatible with parenteral dilution fluids and exhibited mean globule size less than 200 nm. The in vitro hemolysis studies indicated that microemulsions were well tolerated by erythrocytes. The LZM microemulsions containing amino acids exhibited good physical and chemical stability when subjected to refrigeration for 6 months.

Design and evaluation of self-emulsifying drug delivery systems (SEDDS) of nimodipine.

The ability of self-emulsifying drug delivery systems (SEDDS) to improve solubility, dissolution rate and bioavailability of a poorly water-soluble calcium channel blocker, nimodipine (NM) was evaluated in the present investigation. Solubility of NM in various oils, surfactants and cosurfactants was determined. The influence of the ratio of oil to surfactant + cosurfactant, pH of aqueous phase on mean globule size of resulting emulsions was studied by means of photon correlation spectroscopy. The NM loaded SEDDS selected for the in vitro and in vivo studies exhibited globule size less than 180 nm. In vitro dissolution studies indicated that NM loaded SEDDS could release complete amount of NM irrespective of the pH of the dissolution media. Pharmacokinetics of NM suspension, NM oily solution, NM micellar solution and NM SEDDS were evaluated and compared in rabbits. Relative bioavailability of NM in SEDDS was significantly higher than all the other formulations. NM loaded SEDDS were subjected to various conditions of storage as per ICH guidelines for 3 months. NM SEDDS successfully withstood the stability testing.