Recent advances in nanomaterial-based drug delivery systems for melanoma therapy.

Background and Purpose: Safe and effective drug delivery is crucial for the treatment of cancer, which is quite impossible to achieve through traditional methods. Among all types of cancer, skin melanoma is known for its aggressive metastasizing ability and an unprecedented higher degree of lethalness, limiting the overall therapeutic efficacy. Here, we focus on the different types of nanomaterials (NMs) and their drug delivery applications against melanoma. Experimental Approach: All relevant publications, including research papers, reviews, chapters and patents, were assessed using search engines such as Scopus and PubMed, up to the end of August of 2023. The keywords used in the search were: nanomaterials, melanoma, drug delivery routes for melanoma, and nanomaterial-based drug delivery systems (DDS). Most of the publications out of 234 cited in this review are from the last five years. Key Results: The recent advancement and mechanism of action of various NMs against melanoma, including inorganic metallic and carbon-based NMs, organic polymeric and lipid-based NMs, and cell-derived vesicles are discussed. We also focus on the application of different NMs in the delivery of therapeutic agents for melanoma therapy. In addition, the skin and melanoma, genetic mutation and pathways for melanoma, conventional treatment options, and delivery routes for therapeutic agents are also discussed briefly. Conclusion: There are few NM-based DDS developed in the lab set up recently. The findings of this review will pave the path for the development of NM-based DDS on an industrial scale and help in the better management of skin melanoma.

Preparation, characterization, and evaluation (in-vitro, ex-vivo, and in-vivo) of naturosomal nanocarriers for enhanced delivery and therapeutic efficacy of hesperetin.

The present study intends to formulate, characterize and appraise the phospholipid-based nanovesicular system for enhanced delivery of Hesperetin (HT). The quality by design (QbD) approach was employed to prepare Hesperetin naturosomes (HTN) using the solvent evaporation technique and assessed for physicochemical and pharmacological attributes. The FTIR, DSC, and PXRD studies confirmed the successful formation of a vesicular drug-phospholipid complex, while photomicroscopy, SEM, and TEM analysis revealed the morphology of HTN. The functional attributes substantially enhanced the HT's aqueous solubility, drug release, and membrane permeation. The aqueous solubility of HTN was ~10-fold more than that of pure HT. Likewise, the in-vitro dissolution data of HTN showed better competence in releasing the HT (>93%) than the pure HT (~64%) or the physical mixture (~74%). Furthermore, HTN significantly altered HT permeation (>53%) when compared to pure HT (23%) or the physical mixture (28%). The current study showed that naturosomes are a promising way to improve the solubility in water, bioavailability, and therapeutic effectiveness of drugs.

QbD enabled optimization of solvent shifting method for fabrication of PLGA-based nanoparticles for promising delivery of Capecitabine for antitumor activity.

The key objective of the current research was to fabricate and optimize Capecitabine (Cap)-loaded [poly(lactic-co-glycolic acid)] PLGA-based nanoparticles (NPs) by enabling quality by design (QbD) approach for enhancing antitumor activity by promising delivery of the drug at the colonic site. The current research was based on fabricating PLGA-based nanoparticles along with Eudragit S100 as enteric polymer employing solvent shifting method followed by optimization using QbD approach. This approach was found to be useful for understanding the multiple factors and their interaction influencing the product by utilizing Design of Experiment (DOE). Box-Behnken design (BBD) was adopted to achieve the required critical quality attributes (CQAs), i.e., minimizing particle size, maximizing entrapment efficiency, and minimizing PDI value. The optimized nanoparticles were lyophilized and characterized by FT-IR, DSC, TEM, DLS, MTT assay using HT-29 cell lines, and in vivo pharmacokinetic studies. The optimized PLGA-based nanoparticles were found to possess average particle size, PDI, zeta potential, and entrapment efficiency of 195 nm, 0.214, -6.65 mV, and 65%, respectively. TEM analysis revealed the spherical nature of nanoparticles. The FT-IR and DSC studies revealed no interaction. The bioavailability of Cap-loaded nanoparticles was found to be two fold increased than the pure drug, and also, it exhibited significantly more cytotoxic to tumor cells as compared to pure drug as confirmed by MTT assay. The optimized PLGA-based nanoparticles found to possess enhanced bioavailability and significantly more cytotoxic potential as compared to pure drug.

An updated review on application of 3D printing in fabricating pharmaceutical dosage forms.

The concept of "one size fits all" followed by the conventional healthcare system has drawbacks in providing precise pharmacotherapy due to variation in the pharmacokinetics of different patients leading to serious consequences such as side effects. In this regard, digital-based three-dimensional printing (3DP), which refers to fabricating 3D printed pharmaceutical dosage forms with variable geometry in a layer-by-layer fashion, has become one of the most powerful and innovative tools in fabricating "personalized medicine" to cater to the need of therapeutic benefits for patients to the maximum extent. This is achieved due to the tremendous potential of 3DP in tailoring various drug delivery systems (DDS) in terms of size, shape, drug loading, and drug release. In addition, 3DP has a huge impact on special populations including pediatrics, geriatrics, and pregnant women with unique or frequently changing medical needs. The areas covered in the present article are as follows: (i) the difference between traditional and 3DP manufacturing tool, (ii) the basic processing steps involved in 3DP, (iii) common 3DP methods with their pros and cons, (iv) various DDS fabricated by 3DP till date with discussing few research studies in each class of DDS, (v) the drug loading principles into 3D printed dosage forms, and (vi) regulatory compliance.

Lyophilized SLN of Cinnacalcet HCl: BBD enabled optimization, characterization and pharmacokinetic study.

Objective: The objective of the present research is to formulate solid lipid nanoparticles (SLN) of CH to improve its oral bioavailability.Methods: Cinnacalcet hydrochloride (CH) exhibits poor oral bioavailability of 20 to 25% because of low aqueous solubility and first pass metabolism. The SLN formulations were optimized using Box-Behnken Design. SLN formulation was prepared using hot homogenization technique followed by ultra-sonication and evaluated. The optimized SLN formulation was lyophilized to improve the stability of the formulation further.Results: Compritol 888 ATO (COM), Soya lecithin (SL) and poloxamer 188 (POL) were selected as lipid, surfactant and co-surfactant respectively. For optimistaion, the desirable goal was fixed for variour responses vis-a-vis entrapment efficiency (EE), particle size (PS) and (time taken for diffusion of 85% drug) T85%. The optimized single dose of SLN obtained using BBD consisting of 30 mg of CH, 100 mg of COM, 150 mg of SL and 0.1% w/v of POL. The pharmacokinetic study revealed that optimized SLN and lyophilized SLN were found to increase the oral bioavailability nearly two times compared to an aqueous suspension of pure drug.Conclusion: Thus lyophilized SLN formulation explicated the potential of lipid-based nanoparticles as a potential carrier in improving the oral delivery and stability of CH.