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1.
Biomater Adv ; 162: 213903, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38824828

ABSTRACT

AIM: The aim of the present review is to shed light on the nanotechnological approaches adopted to overcome the shortcomings associated with the delivery of venom peptides which possess inherent anti-cancer properties. BACKGROUND: Venom peptides although have been reported to demonstrate anti-cancer effects, they suffer from several disadvantages such as in vivo instability, off-target adverse effects, limited drug loading and low bioavailability. This review presents a comprehensive compilation of different classes of nanocarriers while underscoring their advantages, disadvantages and potential to carry such peptide molecules for in vivo delivery. It also discusses various nanotechnological aspects such as methods of fabrication, analytical tools to assess these nanoparticulate formulations, modulation of nanocarrier polymer properties to enhance loading capacity, stability and improve their suitability to carry toxic peptide drugs. CONCLUSION: Nanotechnological approaches bear great potential in delivering venom peptide-based molecules as anticancer agents by enhancing their bioavailability, stability, efficacy as well as offering a spatiotemporal delivery approach. However, the challenges associated with toxicity and biocompatibility of nanocarriers must be duly addressed. PERSPECTIVES: The everlasting quest for new breakthroughs for safer delivery of venom peptides in human subjects is fuelled by unmet clinical needs in the current landscape of chemotherapy. In addition, exhaustive efforts are required in obtaining and purifying the venom peptides followed by designing and optimizing scale up technologies.


Subject(s)
Antineoplastic Agents , Nanotechnology , Neoplasms , Humans , Neoplasms/drug therapy , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/chemistry , Nanotechnology/methods , Venoms/administration & dosage , Venoms/therapeutic use , Venoms/pharmacokinetics , Venoms/chemistry , Peptides/administration & dosage , Peptides/chemistry , Drug Delivery Systems/methods , Nanoparticles/chemistry , Drug Carriers/chemistry
2.
Nanomedicine (Lond) ; 2024 May 03.
Article in English | MEDLINE | ID: mdl-38700294

ABSTRACT

Aim: To investigate the pemetrexed encapsulated polymeric mixed micelles (PMMs) against breast cancer treatment. Methods: We meticulously optimized the formulation and conducted extensive characterizations, including photon correlation spectroscopy for micellization, advanced analytical techniques and in vitro cell line assessments. Results: The PMM exhibited favorable characteristics, with a spherical morphology, hydrodynamic particle size of 19.58 ± 0.89 nm, polydispersity index of 0.245 ± 0.1, and a surface charge of -9.70 ± 0.61 mV. Encapsulation efficiency and drug payload reached 96.16 ± 0.37% and 4.5 ± 0.32%, respectively. Cytotoxicity analysis indicated superior efficacy of the PMM over the drug solution. Conclusion: The PMM formulation exhibited controlled release of the drug, and demonstrated enhanced cytotoxicity against breast cancer cells, highlighting its therapeutic promise.

3.
Int J Pharm ; 657: 124109, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38626846

ABSTRACT

Breast cancer continues to pose a substantial global health challenge, emphasizing the critical need for the advancement of novel therapeutic approaches. Key players in the regulation of apoptosis, a fundamental process in cell death, are the B-cell lymphoma 2 (Bcl-2) family proteins, namely Bcl-2 and Bax. These proteins have garnered attention as highly promising targets for the treatment of breast cancer. Targeting the overexpressed anti-apoptotic Bcl-2 protein in breast cancer, Gefitinib (GEF), an EGFR (Epidermal Growth Factor Receptor) inhibitor, emerges as a potential solution. This study focuses on designing Gefitinib-loaded polymeric mixed micelles (GPMM) using poloxamer 407 and TPGS (D-alpha tocopherol PEG1000 succinate) for breast cancer therapy. In silico analyses unveil strong interactions between GEF- Bcl-2 and TPGS-Pgp-2 receptors, indicating efficacy against breast cancer. Molecular dynamics simulations offer insights into GEF and TPGS interactions within the micelles. Formulation optimization via Design of Experiment ensures particle size and entrapment efficiency within acceptable ranges. Characterization tools such as zeta sizer, ATR-FTIR, XRD, TEM, AFM, NMR, TGA, and DSC confirms particle size, structure, functional groups, and thermodynamic events. The optimized micelles exhibit a particle size of 22.34 ± 0.18 nm, PDI of 0.038 ± 0.009, and zeta potential of -0.772 ± 0.12 mV. HPLC determines 95.67 ± 0.34% entrapment efficiency and 1.05 ± 0.12% drug loading capacity. In-vitro studies with MDA-MB-231 cell lines demonstrate enhanced cytotoxicity of GPMM compared to free GEF, suggesting its potential in breast cancer therapy. Cell cycle analysis reveals apoptosis induction through key apoptotic proteins. Western blot results confirm GPMM's ability to trigger apoptosis in MDA-MB-231 cells by activating caspase-3, Bax, Bcl-2, and Parp. In conclusion, these polymeric mixed micelles show promise in selectively targeting cancer cells, warranting future in-vivo studies for optimized clinical application against breast cancer.


Subject(s)
Antineoplastic Agents , Breast Neoplasms , Gefitinib , Micelles , Poloxamer , Vitamin E , Humans , Poloxamer/chemistry , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Vitamin E/chemistry , Female , Gefitinib/administration & dosage , Gefitinib/pharmacology , Gefitinib/chemistry , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Molecular Dynamics Simulation , Cell Line, Tumor , Drug Carriers/chemistry , Computer Simulation , Particle Size , Cell Survival/drug effects , Animals , Proto-Oncogene Proteins c-bcl-2/metabolism , Polyethylene Glycols/chemistry , Drug Liberation , Apoptosis/drug effects
4.
Ther Deliv ; 15(4): 279-303, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38374774

ABSTRACT

Breast cancer (BC) is a heterogeneous disease with various morphological features, clinicopathological conditions and responses to different therapeutic options, which is responsible for high mortality and morbidity in women. The heterogeneity of BC necessitates new strategies for diagnosis and treatment, which is possible only by cautious harmonization of the advanced nanomaterials. Recent developments in vesicular nanocarrier therapy indicate a paradigm shift in breast cancer treatment by providing an integrated approach to address current issues. This review provides a detailed classification of various nanovesicles in the treatment of BC with a special emphasis on recent advances, challenges in translating nanomaterials and future potentials.


Subject(s)
Breast Neoplasms , Nanoparticles , Nanostructures , Female , Humans , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Drug Carriers
5.
J Biomol Struct Dyn ; : 1-18, 2024 Jan 21.
Article in English | MEDLINE | ID: mdl-38247232

ABSTRACT

Cyclodextrin complexes loaded with venetoclax for improved solubility and therapeutic efficacy as repurposed drug. The venetoclax-cyclodextrin inclusion complex was prepared using kneading method. Primarily in-silico molecular docking study was performed to examine the possible interaction between venetoclax and hydroxypropyl-ß-cyclodextrin (HP-ß-CD) and extensively characterized. The in-vitro studies were performed using A-549 lung epithelial cancer cells. The in-vivo pharmaco-kinetic studies was performed on wistar rats. The aqueous solubility of venetoclax was increased upto 3.16 folds, as compared with pure venetoclax with entrapment efficiency (EE%) was determined 95.44 ± 0.3%. In-vitro cytotoxicity studies were carried on A-549 lung epithelial cancer cells, wherein BCL-2 receptors were highly over-expressed and IC 50 values for venetoclax and venetoclax- HP-ß-CD complex was calculated at 24 and 48 hrs in the order of 1.241 µg/ml, 0.68 µg/ml and 0.757719 µg/ml, 0.6125 µg/mL, respectively. The oral bioavailability was increased 4.03 times compared to the pure drug. The venetoclax-HP-ß-CD inclusion complexes showed the increased aqueous solubility with improved anticancer activities.Communicated by Ramaswamy H. Sarma.

6.
Drug Deliv Transl Res ; 14(5): 1277-1300, 2024 May.
Article in English | MEDLINE | ID: mdl-37953430

ABSTRACT

Breast cancer is reported as one of the most prevalent non-cutaneous malignancies in women. Venetoclax (VEN) is an approved BCl-2 inhibitor for the treatment of chronic myeloid leukemia with very limited oral bioavailability and exhibits an enormous impact on breast cancer. In the current investigation, venetoclax-loaded self-nanoemulsifying drug delivery systems (VEN-SNEDDS) were designed and fabricated to improve the aqueous solubility, permeability, and anticancer efficacy of VEN. Various surface-active parameters of the reconstituted SNEDDS were determined to scrutinize the performance of the selected surfactant mixture. Central composite design (CCD) was used to optimize the VEN-SNEDDS. The globule size of reconstituted VEN-SNEDDS was 71.3 ± 2.8 nm with a polydispersity index of 0.113 ± 0.01. VEN-SNEDDS displayed approximately 3-4 fold, 6-7 fold, and 5-6 fold reduced IC50 as compared to free VEN in MDA-MB-231, MCF-7, and T47 D cells, respectively. VEN-SNEDDS showed greater cellular uptake, apoptosis, reactive oxygen species generation, and higher BAX/BCL2 ratio with decreased caspase 3 and 8 and BCL-2 levels in the MDA-MB-231 cells compared to pure VEN. VEN-SNEDDS exhibited approximately fivefold enhancement in Cmax and an improved oral bioavailability compared to VEN suspension in in vivo pharmacokinetic studies.


Subject(s)
Breast Neoplasms , Bridged Bicyclo Compounds, Heterocyclic , Nanoparticles , Sulfonamides , Humans , Female , Emulsions , Drug Delivery Systems , Solubility , Surface-Active Agents , Biological Availability , Breast Neoplasms/drug therapy , Proto-Oncogene Proteins c-bcl-2 , Administration, Oral , Particle Size
7.
Biomed Chromatogr ; 38(4): e5815, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38128133

ABSTRACT

The current research involved the development and validation of an easy, cost-effective, and sensitive bioanalytical reverse-phase high-performance liquid chromatography method for the assessment of palbociclib (PAL) in rat plasma and kidney, liver, spleen and heart. A response surface methodology-based Box-Behnken design was used to optimize critical chromatographic conditions such as buffer pH, organic phase concentration and flow rate to attain good sensitivity, tailing factor and retention time. The conditions were: pH of buffer, 4.5; organic phase concentration, 40%; Shimpac column with 1.0 ml/min flow rate. The responses were: tailing factor, 1.29 ± 0.03, sensitivity, 366,593 ± 8,592; and retention time, 4.5 ± 0.05 min. The samples were extracted by a protein precipitation method, and absolute recoveries were in the range of 88.99-95.08%. The linearity of the developed method was validated over the range 100-2,000 ng/ml (r2 ≥ 0.994) in all tested matrices. The developed bioanalytical method showed greater accuracy (0.98 and 4.01%) and precision (<4.88%). The method was optimized for the sensitive analysis of the PAL in rat plasma, and the kidney, liver, spleen and heart were effectively applied to pharmacokinetic studies.


Subject(s)
Chromatography, Reverse-Phase , Pyridines , Rats , Animals , Chromatography, High Pressure Liquid/methods , Piperazines/analysis
8.
Inflammopharmacology ; 31(1): 301-320, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36609718

ABSTRACT

Our main aim is in the present investigation, development and evaluation of seabuckthorn oil-based Emulgel formulation for psoriasis therapy. Anti-psoriatic activity of the SeaEmulgel was studied using Imiquimod-induced psoriasis-like inflammation model Balb/c mice and parameters such as PASI score, ear thickness, spleen to body weight index including histological staining studies, enzyme-linked immune sorbent assay (ELISA), skin compliance and safety evaluation of sea buckthorn oil was performed. The globule size and PDI of sea buckthorn oil emulsion were found to be 172.70 ± 1.73 nm and 0.117 ± 0.018, respectively. In-vivo animal studies performed on male Balb/c mice and emulgel showed a reduction in redness, scaling, inflammation in psoriasis-induced mice, which was analysed by PASI scoring, body weight, spleen weight index and ear thickness. The current investigation clearly revealed the better anti-psoriatic activity of SeaEmulgel formulation against imiquimod-induced psoriasis-like skin inflammation Balb/c mice model.


Subject(s)
Psoriasis , Male , Mice , Animals , Imiquimod/adverse effects , Skin , Inflammation/pathology , Body Weight , Mice, Inbred BALB C , Disease Models, Animal
9.
AAPS PharmSciTech ; 24(1): 26, 2022 Dec 22.
Article in English | MEDLINE | ID: mdl-36550259

ABSTRACT

Essential oils consist of oxygenated structures of secondary metabolites of aromatic plants with anti-psoriatic activities. Tea tree oil (TTO) is an essential oil with good anti-microbial and anti-inflammatory properties, exhibiting reduced levels of IL-1, IL-8, and PGE 2. Thymoquinone (TMQ) is popular herb in traditional medicine with known therapeutic benefits in several diseases and ailments. The ternary phase diagram was prepared with the weight ratio of Smix (Tween® 80:Labrasol®): oil:water ratio for o/w emulsion preparation. The globule size was 16.54 ± 0.13 nm, and PDI around 0.22 ± 0.01 of the TTO-TMQ emulsion and found thermodynamically stable. The percentage drug content was found in the range of 98.97 ± 0.62 to 99.45 ± 0.17% with uniformity of the ThymoGel using Carbopol®. The extensive physicochemical properties were studied using different analytical techniques, and in vitro drug release was performed using Franz-diffusion apparatus. Anti-psoriatic activity of the formulations was studied using Imiquimod-induced psoriasis-like inflammation model in male Balb/c mice and parameters like PASI score, ear thickness, and spleen to body weight index were determined as well as histological staining, ELISA, skin compliance, and safety evaluation of TTO were performed. The combination of essential oils with TMQ shows synergistic activity and efficiently reduces the psoriasis disease condition.


Subject(s)
Oils, Volatile , Psoriasis , Tea Tree Oil , Mice , Animals , Oils, Volatile/pharmacology , Oils, Volatile/metabolism , Emulsions/chemistry , Skin/metabolism , Psoriasis/metabolism
10.
J Control Release ; 352: 1024-1047, 2022 12.
Article in English | MEDLINE | ID: mdl-36379278

ABSTRACT

Breast cancer is the most prevalent non-cutaneous malignancy in women, with greater than a million new cases every year. In the last decennium, numerous diagnostic and treatment approaches have been enormously studied for Breast cancer. Among the different approaches, nanotechnology has appeared as a promising approach in preclinical and clinical studies for early diagnosis of primary tumors and metastases and eradicating tumor cells. Each of these nanocarriers has its particular advantages and drawbacks. Combining two or more than two constituents in a single nanocarrier system leads to the generation of novel multifunctional Hybrid Nanocarriers with improved structural and biological properties. These novel Hybrid Nanocarriers have the capability to overcome the drawbacks of individual constituents while having the advantages of those components. Various hybrid nanocarriers such as lipid polymer hybrid nanoparticles, inorganic hybrid nanoparticles, metal-organic hybrid nanoparticles, and hybrid carbon nanocarriers are utilized for the diagnosis and treatment of various cancers. Certainly, Hybrid Nanocarriers have the capability to encapsulate multiple cargos, targeting agents, enhancement in encapsulation, stability, circulation time, and structural disintegration compared to non-hybrid nanocarriers. Many studies have been conducted to investigate the utilization of Hybrid nanocarriers in breast cancer for imaging platforms, photothermal and photodynamic therapy, chemotherapy, gene therapy, and combinational therapy. In this review, we mainly discussed in detailed about of preparation techniques and toxicological considerations of hybrid nanoparticles. This review also discussed the role of hybrid nanocarriers as a diagnostic and therapeutic agent for the treatment of breast cancer along with alternative treatment approaches apart from chemotherapy including photothermal and photodynamic therapy, gene therapy, and combinational therapy.


Subject(s)
Breast Neoplasms , Metal Nanoparticles , Nanoparticles , Female , Humans , Breast Neoplasms/diagnosis , Breast Neoplasms/drug therapy , Nanoparticles/chemistry , Nanotechnology , Polymers/therapeutic use , Drug Carriers
11.
Pharm Res ; 39(11): 2761-2780, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36171346

ABSTRACT

PURPOSE: Cancer is one of the most common and fatal disease, chemotherapy is the major treatment against many cancer types. The anti-apoptotic BCL-2 protein's expression was increased in many cancer types and Venetoclax (VLX; BCL-2 inhibitor) is a small molecule, which selectively inhibits this specified protein. In order to increase the clinical performance of this promising inhibitor as a repurposed drug, polymeric mixed micelles formulations approach was explored. METHODS: The Venetoclax loaded polymeric mixed micelles (VPMM) were prepared by using Pluronic® F-127 and alpha tocopherol polyethylene glycol 1000 succinate (TPGS) as excipients by thin film hydration method and characteristics. The percentage drug loading capacity, entrapment efficiency and in-vitro drug release studies were performed using HPLC method. The cytotoxicity assay, cell uptake and anticancer activities were evaluated in two different cancer cells i.e. MCF-7 (breast cancer) and A-549 (lung cancer). RESULTS: Particle size, polydispersity index and zeta potential of the VPMM was found to be 72.88 ± 0.09 nm, 0.078 ± 0.009 and -4.29 ± 0.24 mV, respectively. The entrapment efficiency and %drug loading were found to be 80.12 ± 0.23% and 2.13% ± 0.14%, respectively. The IC50 of VLX was found to be 4.78, 1.30, 0.94 µg/ml at 24, 48 and 72 h, respectively in MCF-7 cells and 1.24, 0.68, and 0.314 µg/ml at 24, 48, and 72 h, respectively in A549 cells. Whereas, IC50 of VPMM was found to be 0.42, 0.29, 0.09 µg/ml at 24, 48 and 72 h, respectively in MCF-7 cells and 0.85, 0.13, 0.008 µg/ml at 24, 48 and 72 h in A549 cells, respectively, indicating VPMM showing better anti-cancer activity compared to VLX. The VPMM showed better cytotoxicity which was further proven by other assays and explained the anti-cancer activity is shown through the generation of ROS, nuclear damage,apoptotic cell death and expression of caspase-3,7, and 9 activities in apoptotic cells. CONCLUSION: The current investigation revealed that the Venetoclax loaded polymeric mixed micelles (VPMM) revealed the enhanced therapeutic efficacy against breast and lung cancer in vitro models.


Subject(s)
Lung Neoplasms , Micelles , Humans , Cell Line, Tumor , Polyethylene Glycols , Polymers , Particle Size , Proto-Oncogene Proteins c-bcl-2 , Drug Carriers , Vitamin E
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