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.

Formulation and Evaluation of Resveratrol Loaded Cubosomal Nanoformulation for Topical Delivery.

AIM: The aim of the study was to formulate, characterize, and evaluate the Resveratrol- loaded Cubosomes (RC) for topical application. BACKGROUND: Resveratrol (RV) is a nutraceutical compound with exciting pharmacological potential in different diseases, including cancers. Many studies on resveratrol have been reported for anti- melanoma activity. Due to its low bioavailability, the therapeutic activities of resveratrol are strongly limited. Hence, an approach with nanotechnology has been made to increase its activity through transdermal drug delivery. OBJECTIVE: To formulate, characterize, and evaluate the resveratrol-loaded cubosomes (RC). To evaluate Resveratrol-loaded Cubosomal Gel (RC-Gel) for its topical application. METHODS: RC was formulated by homogenization technique and optimized using a 2-factor 3-level factorial design. Formulated RCs were characterized for particle size, zeta potential, and entrapment efficiency. Optimized RC was evaluated for in vitro release and stability study. Optimized RC was further formulated into cubosomal gel (RC-Gel) using carbopol and evaluated for drug permeation and deposition. Furthermore, developed RC-Gel was evaluated for its topical application using skin irritancy, toxicity, and in vivo local bioavailability studies. RESULTS: The optimized RC indicated cubic-shaped structure with mean particle size, entrapment efficiency, and zeta potential were 113±2.36 nm, 85.07 ± 0.91%, and -27.40 ± 1.40 mV, respectively. In vitro drug release of optimized RC demonstrated biphasic drug release with the diffusion-controlled release of resveratrol (RV) (87.20 ± 3.91%). The RC-Gel demonstrated better drug permeation and deposition in mice skin layers. The composition of RC-Gel has been proved non-irritant to mice skin. In vivo local bioavailability study depicted the good potential of RC-Gel for skin localization. CONCLUSION: The RC nanoformulation proposes a promising drug delivery system for melanoma treatment simply through topical application.

Pharmacokinetic and Pharmacodynamic Evaluation of Resveratrol Loaded Cationic Liposomes for Targeting Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. The destructive nature of the disease makes it difficult for clinicians to manage the condition. Hence, there is an urgent need to find new alternatives for HCC, as the role of conventional cytotoxic drugs has reached a plateau to control HCC associated mortality. Antioxidant compounds of plant origin with potential anti-tumor effect have been recognized as alternate modes in cancer treatment and chemoprevention. Resveratrol (RS) is a model natural nonflavonoid drug known for its anti-cancer activity. However, its clinical application is limited due to its poor bioavailability. The current research work aims to formulate, optimize, and characterize RS loaded cationic liposomes (RLs) for specific delivery in HCC. The optimized liposomes formulation (RL5) was spherical with a vesicle size (VS) of 145.78 ± 9.9 nm, ζ potential (ZP) of 38.03 ± 9.12 mV, and encapsulation efficiency (EE) of 78.14 ± 8.04%. In vitro cytotoxicity studies in HepG2 cells demonstrated an improved anti-cancer activity of RL5 in comparison with free RS. These outcomes were supported by a cell uptake study in HepG2 cells, in which RL5 exhibited a higher uptake than free RS. Furthermore, confocal images of HepG2 cells after 3 and 5 h of incubation showed higher internalization of coumarin 6 (C6) loaded liposomes (CL) as compared to those of the free C6. Pharmacokinetic and pharmacodynamic (prophylactic and therapeutic treatment modalities) studies were performed in N-nitrosodiethylamine (NDEA-carcinogen) induced HCC in rats. Pharmacokinetic evaluation of RL5 demonstrated increased localization of RS in cancerous liver tissues by 3.2- and 2.2-fold increase in AUC and Cmax, respectively, when compared to those of the free RS group. A pharmacodynamic investigation revealed a significant reduction in hepatocyte nodules in RL5 treated animals when compared to those of free RS. Further, on treatment with RL5, HCC-bearing rats showed a significant decrease in the liver marker enzymes (alanine transaminase, alkaline phosphatase, aspartate transaminase, total bilirubin levels, γ-glutamyl transpeptidase, and α-fetoprotein), in comparison with that of the disease control group. Our findings were supported by histopathological analysis, and we were first to demonstrate that NDEA induced detrimental effect on rat livers was successfully reversed with the treatment of RL5 formulation. These results implied that delivery of RS loaded cationic liposomes substantially controlled the severity of HCC and that they can be considered as a promising nanocarrier in the management of HCC.

Local drug delivery systems in the management of periodontitis: A scientific review.

Periodontitis (PD) is a microbial disease of tooth supporting tissues that results in progressive destruction of surrounding soft and hard tissues with eventual tooth mobility and exfoliation. Perioceutics, which includes the delivery of therapeutic agents via systemic and local means as an adjunct to mechanical therapy has revolutionized the arena of periodontal therapy. Selection of a right antimicrobial agent with appropriate route of drug administration is the key to successful periodontal therapy. Irrigating systems, fibers, gels, strips, films, microparticles, nanoparticles and low dose antimicrobial agents are some of the local drug delivery systems (LDDS) available in the field, which aims to deliver antimicrobial agents to sub-gingival diseased sites with minimal or no side-effects on other body sites. The present review aim to summarize the current state-of-the-art technology on LDDS in periodontal therapy ensuring the the practitioners are able to choose LDD agents which are custom made for a specific clinical condition.

A validated stability-indicating HPLC method for simultaneous estimation of resveratrol and piperine in cubosome and human plasma.

Resveratrol and piperine are proven for their therapeutic benefits to treat various diseases. Due to their synergistic actions and combined drug delivery application, a rapid and specific RP-HPLC method was developed and validated as per ICH guidelines, by using an isosbestic point. The chromatographic separation was performed with Luna 5 µ 100 ŠC-18(2) HPLC column by using acetonitrile (ACN): phosphate buffer (0.01% orthophosphoric acid) (55:45) as mobile phase, at 1 mL/min of flow rate and 330 nm. The developed method was found to be linear over the concentration range of 0.25-8 µg/mL with correlation coefficient value >0.999. The developed method was accurate (percent recovery 98.06-101.74%), precise (percent relative standard deviation <2.0%), and robust. The limit of detection and limit of quantification for resveratrol were found to be 0.02 and 0.08 µg/mL, respectively and 0.04 and 0.11 µg/mL, for piperine, respectively. The developed method was also validated in human plasma as per ICH guidelines. Moreover, stress degradation studies of both phytoconstituents were studied and the relevancy of the developed method was analyzed on cubosome nanoformulation. A good separation of drug peaks was observed in the presence of the degradation products. This method could thus be used for regular in vitro and in vivo estimation of piperine and resveratrol.

Preparation, Optimization, and In Vivo Evaluation of Nanoparticle-Based Formulation for Pulmonary Delivery of Anticancer Drug.

Background and Oobjectives: Lung cancer, a pressing issue in present-day society due to its high prevalence and mortality rate, can be managed effectively by long-term delivery of anticancer agents encapsulated in nanoparticles in the form of inhalable dry powder. This approach is expected to be of strategic importance in the management of lung cancer and is a developing area in current research. In the present investigation, we report on the formulation and characterization of docetaxel inhalable nanoparticles as a viable alternative for effective treatment of non-small cell lung cancer as a long-term delivery choice. Materials and Methods: Poloxamer (PLX-188) coated poly (lactic-co-glycolic acid) (PLGA) nanoparticles containing docetaxel (DTX-NPs) were prepared by simple oil in water (o/w) single emulsification-solvent evaporation process. The nanoparticles were collected as pellet by centrifugation, dispersed in mannitol solution, and lyophilized to get dry powder. Results: Optimized DTX-NPs were smooth and spherical in morphology, had particle size around 200 nm, zeta potential around -36 mV, and entrapment efficiency of around 60%. The invitro anticancer assay was assessed and it was observed that nanoparticle-based formulation exhibited enhanced cytotoxicity when compared to the free form of the drug post 48 h. On examining for invitro drug release, slow but continuous release was seen until 96 h following Higuchi release kinetics. DTX-NPs were able to maintain their desired characteristics when studied at accelerated conditions of stability. Conclusions: In-vivo study indicated that the optimized nanoparticles were well retained in lungs and that the drug level could be maintained for a longer duration if given in the form of DTX-NPs by the pulmonary route. Thus, the non-invasive nature and target specificity of DTX-NPs paves the way for its future use as a pulmonary delivery for treating non-small cell lung cancer (NSCLC).

Phytosynthesis of gold nanoparticles: Characterization, biocompatibility, and evaluation of its osteoinductive potential for application in implant dentistry.

Gold nanoparticles have been extensively used in diagnostics, biomedical imaging, and drug delivery owing to simple method of synthesis and versatile surface functionalization. Present investigation aims to evaluate the osteoinductive property of Salacia chinensis (SC) mediated gold nanoparticles (GNPs) for its application in implant dentistry. The formation of GNPs was assessed initially using the visual method and characterized analytically by using UV-visible spectroscopy, Zetasizer, X-RD, ICP-AES, AFM, and TEM. Green synthesized GNPs exhibited a remarkable stability in various blood components (0.2 M histidine, 0.2 M cysteine 2% bovine serum albumin, and 2% human serum albumin) and were found to be nontoxic when evaluated for their cytocompatibility and blood compatibility using periodontal fibroblasts and erythrocytes respectively. Exposure of GNPs to MG-63 cell lines displayed increased percent cell viability (138 ±â€¯27.4) compared to the control group (96 ±â€¯3.7) which confirms its osteoinductive potential. Herein, it can be concluded that the stable, biocompatible and eco-friendly GNPs can be used as an effective bone inductive agent during dental implant therapy.

Phytosynthesis of Silver Nanoparticles: Characterization, Biocompatibility Studies, and Anticancer Activity.

Silver nanoparticles (SNPs), owing to their wide range of biomedical applications, have recently attracted remarkable interest for use in cancer nanomedicine. The present research work investigated the anticancer activity of phytosynthesized SNPs against human cancer cell lines. Phytosynthesis of SNPs was achieved by using an aqueous extract of Salacia chinensis (SC) bark as a green source to reduce silver nitrate to silver nanoparticles. Characterization of synthesized nanoparticles demonstrated a UV-visible peak at 443 nm, ζ-potential (zetasizer) of -25.6 ± 0.34 and particle size (transmission electron microscopy analysis) in the range of 40-80 nm, which validates formation of stable silver nanoparticles. The absence of cytotoxicity against normal human fibroblasts and blood erythrocytes confirms the biocompatible nature of green synthesized SNPs. In vitro anticancer assay demonstrated IC50 values of 6.31, 4.002, 5.228, 8.452, 14.37, 7.46, and 6.55 µg/mL against liver (Hep G2), lungs (L-132), pancreas (MIA-Pa-Ca-2), breast (MDA-MB-231), oral (KB cells), prostate (PC-3), and cervical (HeLa) cancer cell lines respectively, which confirms its potent anticancer action. The results of the present study give an experimental proof that the SC mediated green synthesized SNPs could serve as a promising anticancer agent to overcome limitations of existing conventional cancer chemotherapeutics.

Formulation of thermoreversible gel of cranberry juice concentrate: Evaluation, biocompatibility studies and its antimicrobial activity against periodontal pathogens.

The present work aims to investigate the efficacy of thermoreversible gel of cranberry juice concentrate (CJC) as local drug delivery for the treatment of periodontitis. CJC was initially tested for its antimicrobial activities like MIC, MBC, antiadhesion, antibiofilm and time kill assay against the panel of organisms (S. mutans (SM), E. faecalis (EF), A. actinomycetemcomitans (AA), P. gingivalis (PG), T. forsythia (TF)) responsible for periapical and periodontal infections. Antimicrobial activity of CJC showed MIC value of 50mg/ml and MBC value of 100mg/ml with desirable antiadhesion (83-90%) and antibiofilm activity (70-85%). CJC was evaluated for its biocompatibility using periodontal fibroblasts by cell based MTT assay and found to be nontoxic. Influence of CJC on periodontopathogen PG derived virulence factors (fimA and kgp) was studied using real time polymerase chain reaction (RT-PCR) technique wherein down regulation of selected genes demonstrated inhibitory effect against PG virulence factors. Thermoreversible gel of CJC was formulated by cold method using poloxamer 407 as thermosensitive polymer and carbopol 934 as mucoadhesive polymer and evaluated for its gelation temperature, viscosity, gel strength and mucoadhesive strength. Comparison of optimized thermoreversible gel of CJC (500mg/ml) with commercially available chlorhexidine gluconate gel (0.2%) using agar well diffusion demonstrated equal zone of inhibition against SM, EF, AA, PG & TF. Hence the formulated thermoreversible gel of CJC could serve as a novel herbal alternative to currently available periodontal treatment modalities.

Doxorubicin loaded gold nanoparticles: Implication of passive targeting on anticancer efficacy.

The present work aims to investigate targeting potential of doxorubicin (Dox) functionalized gold nanoparticles (D-GNPs) for treatment of chemically induced fibrosarcoma in mice. Carrier GNPs were synthesised by green chemistry method and loaded with doxorubicin by incubation method. D-GNPs were studied for its biocompatibility using normal mouse fibroblasts (L929) and found to be cell compatible and non-toxic. D-GNPs (at a dose of 2.5, 2 and 1.5mg/kg equivalent to Dox) demonstrated passive targeting measured as function of antitumor efficacy against chemical induced fibrosarcoma which showed higher latency to the tumour growth as compared to free Dox (2.5mg/kg). D-GNPs exhibited significantly higher therapeutic anticancer efficacy (∼81% tumour suppression at dose of 2.5mg/kg equivalent to Dox) in the same model as compared to that of free doxorubicin (∼48% tumour suppression at dose of 2.5mg/kg). Safety profile and targeting efficiency of developed formulation was established by assessing cardiac and blood markers.