In this study, nanogel creams carrying paclitaxel (PTX) and temozolomide (TMZ) were prepared for the topical treatment of melanoma. PTX and TMZ were first loaded in ...poly-(D,L-lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly-(D,L-lactide-co-glycolide) (PLAG-b-PEG-b-PLGA) thermosensitive nanogels, which made a transition from a free-flowing sol (formation of micellar network) at 25°C with the z-average particle size of c.a. 96 nm to a gel (aggregation of micelles) at 33°C with the z-average particle size of c.a. 427 nm. An anhydrous absorption ointment base, aquaphor, was then added to drug-loaded nanogels to form nanogel creams carrying PTX and TMZ. Nanogel creams permitted controlled release of the payloads and improved the penetration of the payloads through the rodent skin compared to drug(s)-loaded nanogels. PTX and TMZ in a combination were synergistically effective in inhibiting SK-MEL28, A375, and B16-F10 melanoma cancer cells
in vitro
. Topically applied nanogel creams carrying TMZ/PTX (4 mg/1.5 mg/dose) showed a trend of tumor volume inhibition on B16-F10-bearing xenograft mice
in vivo
.
Neurodegenerative disorders (NDs) are expected to pose a significant challenge for both medicine and public health in the upcoming years due to global demographic changes. NDs are mainly represented ...by degeneration/loss of neurons, which is primarily accountable for severe mental illness. This neuronal degeneration leads to many neuropsychiatric problems and permanent disability in an individual. Moreover, the tight junction of the brain, blood-brain barrier (BBB)has a protective feature, functioning as a biological barrier that can prevent medicines, toxins, and foreign substances from entering the brain. However, delivering any medicinal agent to the brain in NDs (i.e., Multiple sclerosis, Alzheimer's, Parkinson's, etc.) is enormously challenging. There are many approved therapies to address NDs, but most of them only help treat the associated manifestations. The available therapies have failed to control the progression of NDs due to certain factors, i.e., BBB and drug-associated undesirable effects. NDs have extremely complex pathology, with many pathogenic mechanisms involved in the initiation and progression; thereby, a limited survival rate has been observed in ND patients. Hence, understanding the exact mechanism behind NDs is crucial to developing alternative approaches for improving ND patients' survival rates. Thus, the present review sheds light on different cellular mechanisms involved in NDs and novel therapeutic approaches with their clinical relevance, which will assist researchers in developing alternate strategies to address the limitations of conventional ND therapies. The current work offers the scope into the near future to improve the therapeutic approach of NDs.
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•Advancement in nanotechnology is a boon for cellular repair in mental disorders.•Molecular mechanisms in NDs could augment mental illness therapies and research.•Clinical insights may improve understanding of limits and benefits of NDs therapies.
The poor permeability and low bioavailability of vitamin B12 (vit. B12) through the mucosal lining of lungs are required substitutes. Therefore, the present work aims to develop a dry powder inhaler ...(DPI) of (Vit.B12) encapsulated into bovine serum albumin (BSA) followed by pullulan coated micro particles (Vit.B12-Pull-BSA) through spray drying. Briefly, pullulan was used as a mucoadhesive agent whereas BSA was used as an encapsulating agent. The obtained Vit.B12-Pull-BSA micro-particles were characterized using different in-vitro spectroscopic techniques, in vitro dissolution, mucoadhesion study, particle size analysis, etc. As a result, the surface morphology of Vit.B12-Pull-BSA micro-particles shows spherical micro-particle with circular surface morphology that can be suitable for pulmonary drug delivery. The PXRD study reveals the conversion of the crystalline nature of vitamin B12 to amorphous nature. Particle size showed 590.1 nm and zeta potential of microparticles was −27.3 mV respectively, which indicates the good stability of particles. The in-vitro assessment of Vit.B12-Pull-BSA microparticles using cascade Impactor revealed that 90.8 ± 1.1% of dry powder formulation was emitted from the device whereas 64.1 ± 6.8% of vitamin B12 loaded particles were reached at a fine stage that suggests preferential delivery of micro-particle. Male Wister rats were utilized for pharmacokinetic analysis through intratracheal administration of Vit.B12-Pull-BSA micro-particles that confirmed the increase in the permeability. Accordingly, it increases the 4.5 folds' relative bioavailability of vitamin B12. In conclusion, the Vit.B12-Pull-BSA micro-particles-based DPI offers improved permeability and bioavailability that can provide the alternative for conventional drug delivery.
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•Microparticles containing vit. B 12 based on pullulan and BSA were developed.•Microparticles characterized for various parameters.•In vitro DPI characterization of microparticles demonstrated alveolar deposition in lungs.•In vivo studies relative concentration of vitamin b12 in lungs.
Cystic fibrosis is the predominant autosomal recessive disorder known to reduce life expectancy. Research findings indicate that around 60 to 70% of adult individuals with this condition carry ...infections of Pseudomonas aeruginosa.
The ongoing research investigates the potential synergy of merging ivacaftor and ciprofloxacin to address bacterial infections.
The two drugs were spray-dried into microparticles, which were then coated with Lsalbutamol and were to be delivered by a dry powder inhaler. Microparticles were generated by applying the spray drying method, utilizing bovine serum albumin and L-leucine in their preparation. Additionally, L-salbutamol was mixed and adsorbed onto the surface of the spray-dried microparticles, and it acted as a bronchodilator.
The microparticles produced via spray drying exhibited a particle size measuring 1.6 ± 0.04 μm, along with a polydispersity ratio of 0.33. Their zeta potential measured -27.3 ± 1.1 mV, while the mass median aerodynamic diameter of these microparticles was 3.74 ± 0.08 μm. SEM, XRD, and FTIR studies confirmed the entrapment of ivacaftor and ciprofloxacin. The morphology was observed by SEM and TEM scans. Antibacterial synergy was confirmed through the agar broth and dilution method, and the formulation's safety was established based on the outcomes of the MTT assay.
Using spray-dried microparticles containing ciprofloxacin, ivacaftor, and L-salbutamol presents a novel approach to the treatment of cystic fibrosis.
Paclitaxel (PTX) is an essential anticancer drug from the biopharmaceutical classification system (BCS) class IV. Unfortunately, PTX has some drawbacks including low solubility, cell toxicity, ...adverse cell reaction, etc. Therefore, folic acid (FA) tailored carboxymethyl-dextran (CMD), and bovine serum albumin (BSA) mediated nanoconjugates of paclitaxel (PTX) (FA-CMD-BSA-PTX) were designed. At first, esterification reaction between FA and CMD resulted in FA-CMD conjugate whereas FA-CMD-BSA conjugate was synthesized via the Maillard reaction. Finally, FA-CMD-BSA conjugates of PTX were achieved via hydrophobic interaction and gelation of BSA. Herein, heating offers the gelation of BSA that furnishes the cross-linking wherein PTX gets fixed inside BSA. Thermogram of FA-CMD-BSA-PTX showed the absence of PTX peak that concluding PTX has been molecularly dispersed in polymer matrix and entrapment inside polymeric conjugate. As an effect, surface decorated FA-CMD-BSA-PTX showed low hemolytic toxicity over free PTX. Cytotoxicity assay on A549 human lung cancer cells shows cell viability decreased from 60 % to 10 % with increasing concentration from 1 to 5 μg/mL. In conclusion, CMD facilitates the circulation time of PTX and BSA acts as a carrier to target tumor locations effectively. The nano-conjugate formulation significantly reduces toxicity and can be used for the treatment of lung cancer.
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•Non-small cell lung cancer accounts for 85 % of lung cancer.•Folic acid-tailored carboxymethyl-dextran and bovine serum albumin-based nanoconjugates of paclitaxel were designed.•Folic acid on the nanoconjugates surface enables the conjugate to target folate receptor-over expressed in tumor.•Anticipated folic acid-tailored paclitaxel nanoconjugates improved the anticancer activity in human lung cancer cells.•The design of surface-tailored carboxymethyl dextran-protein-based nanoconjugates will provide a new alternative for paclitaxel delivery.
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.
This review highlights the importance of the pharmacokinetics of vitamins in maintaining human health and offers reliable evidence for their efficacy in the human body. Effective delivery of vitamins is desired to avoid their deficiency, and therefore, alternate routes of administration could improve the pharmacokinetics of vitamins. Nanoformulation‐based delivery is a feasible strategy to improve vitamin delivery.
Exosomes are multivesicular bodies of which the plasma membrane fuse to release the caring moiety into the surrounding body fluids. They are well knwon for their function in mediating intercellular ...connectivity by transferring various biomolecules, such as proteins, RNAs, and lipids, from one cell to another. These “naturally equipped” nanovesicles could be therapeutically targeted or engineered as drug delivery systems. The use of exosomes in cancer detection and prognosis has attracted a great deal of interest from academics. In addition to chemical, biological, and genetic engineering approaches, other current exosomal alteration methodologies hold promise for the advancement of therapeutic medicines for cancer. In this review, we highlight the theranostic potential of exosomes for therapeutic delivery in various cancers.
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