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1.
Prog Mol Biol Transl Sci ; 209: 165-182, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39461751

RESUMO

Glioblastoma (GBM) is a highly proliferative, lethal cancer of the brain. The median survival at eight months is ca. 6.8%. Resistance towards the anti-glioblastoma drug temozolomide (TMZ), recurrence of cancer cells, blood-tumor brain barrier (BTBB), blood-brain barrier (BBB), and tumor immunosuppression are major challenges in treating GBM. Drug delivery systems employing TMZ and other anti-cancer drugs and combination therapy (temozolomide with immunotherapeutics) are under pre-clinical and clinical studies, respectively. Immunotherapeutics have emerged as a dominant mechanism to silence tumor development and dissemination. Paradoxically, immunotherapy has witnessed failure in treating GBM. This is due to the unique immunosuppressive microenvironment in GBM. Future immunotherapeutics with inherent tumor environment-modulating properties have to be identified. In this review, we discuss recent delivery systems and devices engineered to deliver immunotherapeutics with the ability to alter/silence tumor immune suppression.


Assuntos
Neoplasias Encefálicas , Sistemas de Liberação de Medicamentos , Glioblastoma , Imunoterapia , Microambiente Tumoral , Humanos , Glioblastoma/terapia , Glioblastoma/imunologia , Glioblastoma/patologia , Glioblastoma/tratamento farmacológico , Microambiente Tumoral/efeitos dos fármacos , Imunoterapia/métodos , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/tratamento farmacológico , Animais
2.
AAPS PharmSciTech ; 25(7): 216, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39289249

RESUMO

This study aimed to develop paclitaxel (PTX)-loaded PEGylated (PEG)-pH-sensitive (SpH) liposomes to enhance drug delivery efficiency and cytotoxicity against MCF-7 breast cancer cells. PTX-loaded PEG-SpH liposomes were prepared using the thin film hydration method. ATR-FTIR compatibility studies revealed no significant interactions among liposome formulation components. TEM images confirmed spherical morphology, stability, and an ideal size range (180-200 nm) for improved blood circulation. At pH 5.5, liposomes exhibited increased size and positive zeta potential, indicating pH-sensitive properties due to CHEMS response to the acidic tumor microenvironment. Conversely, at pH 7.4, liposomes showed a slightly larger size (199.25 ± 1.64 nm) and a more negative zeta potential (-36.94 ± 0.32 mV), suggesting successful PEG-SpH surface modification, enhancing stability, and reducing aggregation. PTX-loaded PEG-SpH liposomes demonstrated high encapsulation efficiency (84.57 ± 0.92% w/w) and drug loading capacity (4.12 ± 0.26% w/w). In-vitro drug release studies revealed accelerated first-order PTX release at pH 5.5 and a controlled zero-order release at pH 7.4. Cellular uptake studies on MCF-7 cells demonstrated enhanced PTX uptake, attributed to mPEG-PCL incorporation prolonging circulation time and CHEMS facilitating PTX release in the tumor microenvironment. Furthermore, PTX-loaded PEG-SpH liposomes exhibited significantly improved cytotoxicity with an IC50 value of 1.107 µM after 72-h incubation, approximately 90% lower than plain PTX solution. Stability studies confirmed the robustness of the liposomal formulation under various storage conditions. These findings highlight the potential of PEGylated pH-responsive liposomes as effective nanocarriers for enhancing PTX therapy against breast cancer.


Assuntos
Neoplasias da Mama , Liberação Controlada de Fármacos , Lipossomos , Paclitaxel , Polietilenoglicóis , Paclitaxel/administração & dosagem , Paclitaxel/farmacologia , Paclitaxel/farmacocinética , Paclitaxel/química , Humanos , Lipossomos/química , Células MCF-7 , Concentração de Íons de Hidrogênio , Polietilenoglicóis/química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/química , Tamanho da Partícula , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos
3.
Int J Pharm ; 664: 124566, 2024 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-39154918

RESUMO

Glaucoma is caused by high intraocular pressure, which can causes blindness. Combinations of timolol and dorzolamide are used for its treatment with a requirement of multiple dosing with dosing being twice or four times a day. Conventional eye drops have poor pre-corneal retention and is thus less available for action. This study utilizes principles of Quality by Design for formulation of injectable liposomes coloaded with timolol maleate and dorzolamide HCl, which overcomes limitations of conventional eye drops. For implementation of Quality by Design principles a systematic approach involving defining Quality Target Product Profile, identification of Critical Quality Attributes, mapping Critical Quality Attributes to Critical Process Parameters and Critical Material Attributes, Failure Mode and Effect Analysis based risk assessment, Taguchi screening, and 32 full factorial Design of Experiments design were utilized. A robust model for formulation of coloaded liposomes was successfully developed. Design of Experiments approach allowed to obtain optimized batch having particle size of 116.1 nm, encapsulation efficiency of dorzolamide HCl of 72.12 % and encapsulation efficiency of timolol maleate of 71.94 %. In-vitro drug release showed a sustained release for 4 days. The prepared formulation was in the desired osmolarity range. Biosafety was proved using histopathological characterization. In-vivo studies for assessing the Intra Ocular Pressure reduction showed that there was no significant difference in Intra Ocular Pressure reduction between prepared liposomes and marketed formulation but were superior than marketed formulation because of less fluctuations in Intra Ocular Pressure. Prepared coloaded injectable liposomes lays the foundation for further research in the area and can be translated from to bench side for commercial clinical use.


Assuntos
Liberação Controlada de Fármacos , Pressão Intraocular , Lipossomos , Sulfonamidas , Tiofenos , Timolol , Timolol/administração & dosagem , Timolol/química , Timolol/farmacocinética , Sulfonamidas/administração & dosagem , Sulfonamidas/química , Sulfonamidas/farmacocinética , Tiofenos/administração & dosagem , Tiofenos/química , Animais , Pressão Intraocular/efeitos dos fármacos , Composição de Medicamentos/métodos , Tamanho da Partícula , Coelhos , Masculino , Combinação de Medicamentos , Química Farmacêutica/métodos , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/química , Anti-Hipertensivos/farmacocinética , Glaucoma/tratamento farmacológico
4.
Nanomedicine (Lond) ; 19(26): 2211-2227, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38934510

RESUMO

Aim: Paclitaxel and imatinib mesylate are drugs used in the treatment of breast cancer. Conventional drug-delivery systems have limitations in the effective treatment of breast cancer using the drugs.Materials & methods: Combination index studies were used to identify the optimum ratio of both drugs showing maximum synergistic effect. Using a systematic quality-by-design approach, protamine-coated PLGA nanoparticles co-loaded with paclitaxel and imatinib mesylate were formulated. Further characterization and cell line evaluations were performed.Results: Encapsulation efficiency obtained was 92.54% for paclitaxel and 75.12% for imatinib mesylate. A sustained (24 h) and controlled zero-order drug release was obtained.Conclusion: Formulated nanoparticles had a low IC50 value and enhanced cellular uptake.


[Box: see text].


Assuntos
Neoplasias da Mama , Liberação Controlada de Fármacos , Mesilato de Imatinib , Nanopartículas , Paclitaxel , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Protaminas , Mesilato de Imatinib/farmacologia , Mesilato de Imatinib/química , Humanos , Paclitaxel/farmacologia , Paclitaxel/química , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Feminino , Nanopartículas/química , Linhagem Celular Tumoral , Protaminas/química , Portadores de Fármacos/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Tamanho da Partícula
5.
Ther Deliv ; 15(6): 427-447, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38722230

RESUMO

Aim: This study aimed to formulate erlotinib hydrochloride (ERT-HCL)-loaded chitosan (CS) and poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) using Quality-by-Design (QbD) to optimize critical quality attributes (CQAs). Materials & methods: Quality target product profile (QTPP) and CQAs were initially established. Based on L8-Taguchi screening and risk assessments, central composite design (CCD) design was used to optimize NPs. Results: ERT-HCL-loaded CS-PLGA NPs had a mean particle diameter, zeta potential and entrapment efficiency of 226.50 ± 1.62 d.nm, 27.66 ± 0.64 mV and 78.93 ± 1.94 %w/w, respectively. The NPs exhibited homogenous spherical morphology and sustained release for 72 h. Conclusion: Using systematic QbD approach, ERT-HCL was encapsulated in CS-PLGA NPs, optimizing CQAs. These findings propel future research for improved NSCLC treatment.


Innovative erlotinib-loaded chitosan-PLGA nanoparticles, developed through a systematic QbD approach, promise enhanced drug delivery for NSCLC. Optimized for size, potential and entrapment efficiency, these particles demonstrate sustained release over 72 h. #DrugDelivery #QBD #NSCLC.


Assuntos
Quitosana , Cloridrato de Erlotinib , Ácido Láctico , Nanopartículas , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Cloridrato de Erlotinib/administração & dosagem , Cloridrato de Erlotinib/química , Quitosana/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Nanopartículas/química , Ácido Láctico/química , Ácido Poliglicólico/química , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Química Farmacêutica/métodos , Preparações de Ação Retardada , Antineoplásicos/administração & dosagem , Antineoplásicos/química
6.
Drug Dev Ind Pharm ; 50(5): 420-431, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38502031

RESUMO

OBJECTIVE: The study was aimed at formulating temozolomide (TMZ) loaded gelatin nanoparticles (GNPs) encapsulated into polyvinyl alcohol (PVA) nanofibers (TMZ-GNPs-PVA NFs) as the nano-in-nanofiber delivery system. The secondary objective was to explore the sustained releasing ability of this system and to assess its enhanced cellular uptake against U87MG glioma cells in vitro. SIGNIFICANCE: Nano-in-nanofibers are the emerging drug delivery systems for treating a wide range of diseases including cancers as they overcome the challenges experienced by nanoparticles and nanofibers alone. METHODS: The drug-loaded GNPs were formulated by one-step desolvation method. The Design of Experiments (DoE) was used to optimize nanoparticle size and entrapment efficiency. The optimized drug-loaded nanoparticles were then encapsulated within nanofibers using blend electrospinning technique. The U87MG glioma cells were used to investigate the uptake of the formulation. RESULTS: A 32 factorial design was used to optimize the mean particle size (145.7 nm) and entrapment efficiency (87.6%) of the TMZ-loaded GNPs which were subsequently ingrained into PVA nanofibers by electrospinning technique. The delivery system achieved a sustained drug release for up to seven days (in vitro). The SEM results ensured that the expected nano-in-nanofiber delivery system was achieved. The uptake of TMZ-GNPs-PVA NFs by cells was increased by a factor of 1.964 compared to that of the pure drug. CONCLUSION: The nano-in-nanofiber drug delivery system is a potentially useful therapeutic strategy for the management of glioblastoma multiforme.


Assuntos
Preparações de Ação Retardada , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Nanofibras , Nanopartículas , Tamanho da Partícula , Álcool de Polivinil , Temozolomida , Temozolomida/administração & dosagem , Temozolomida/farmacocinética , Temozolomida/farmacologia , Humanos , Nanofibras/química , Linhagem Celular Tumoral , Álcool de Polivinil/química , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Glioma/tratamento farmacológico , Glioma/metabolismo , Portadores de Fármacos/química , Gelatina/química , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/farmacocinética
7.
Daru ; 32(1): 161-175, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38158475

RESUMO

BACKGROUND: Increased intraocular pressure is a common symptom of glaucoma. In severe circumstances, it may result in loss of eyesight. Glaucoma treatment is difficult due to ocular physiological barriers that prevent medications from reaching the afflicted area. Traditional formulations (eye drops) have a short residence period and are rapidly drained away via the nasolacrimal duct, resulting in increased adverse drug responses and lower efficacy. The usage of nanoparticles such as niosomes could be one potential answer to these problems. While niosomes improve drug penetration, they have little effect on ocular retention of the medication. Contact lenses containing niosomes can assist to overcome this disadvantage. OBJECTIVE: This study aims to prepare and evaluate Brimonidine niosomes laden contact lenses for the treatment of Glaucoma. METHODS: Brimonidine niosomes were prepared using thin film hydration method and evaluated. The contact lenses were soaked in the niosomal formulation at varying intervals (3-10 days). Thereafter, the contact lenses were evaluated for %transmittance, %swelling index, drug quantification and in vitro drug release. The pharmacodynamic studies were conducted to assess the reduction in intraocular pressure (IOP) in albino rabbits. The research compared the results of the reduction in intraocular pressure caused by Brimonidine niosomes laden contact lenses with a marketed preparation of niosomes. RESULTS: Higher concentration of the drug was loaded in contact lenses loaded with Brimonidine niosomes compared to the marketed formulation, by soaking method. The contact lenses exhibited an optimal %transmittance of 98.02 ± 0.36 and %swelling index of 50.35 ± 0.57. Increase in the soaking time up to 7 days led to an increase in the drug concentration in the contact lenses. However, no further increase was observed after the 7th day due to saturation of the contact lenses. Brimonidine niosomes laden contact lenses provided a reduction in intraocular pressure that was similar to the marketed preparation. Further, the contact lenses provided extended release up to 20 h. CONCLUSION: Brimonidine niosomes laden contact lenses exhibited superior drug loading through the soaking method, displaying optimal %transmittance and %swelling index. Soaking for 7 days increased drug concentration in contact lenses with no further increase due to saturation. These lenses reduced intraocular pressure like the marketed formulation, offering extended release for 20 h.


Assuntos
Tartarato de Brimonidina , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Glaucoma , Pressão Intraocular , Lipossomos , Tartarato de Brimonidina/administração & dosagem , Tartarato de Brimonidina/farmacologia , Animais , Coelhos , Glaucoma/tratamento farmacológico , Glaucoma/terapia , Pressão Intraocular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Lentes de Contato , Masculino
8.
Nanomedicine (Lond) ; 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37991004

RESUMO

Background: Bimatoprost is a drug used to lower intraocular pressure in the treatment of glaucoma. Conventional eye drops have the limitations of repeated dosing, drug loss due to tear outflow and hence poor availability for action. Materials & methods: Using a systematic quality by design approach, liposomes and solid lipid nanoparticles were formulated and further encapsulated in thermo-sensitive in situ hydrogel. Results & conclusion: Optimized liposomes had 87.04% encapsulation efficiency and 306.78 nm mean particle size, while solid lipid nanoparticles had 90.51% and 304.21 nm. Bimatoprost liposomes had controlled zero-order drug kinetics and no initial burst release, making them better than solid lipid nanoparticles. Bimatoprost-loaded liposomes in thermo-sensitive hydrogel decreased intraocular pressure for 18 h.

9.
Pharm Dev Technol ; 28(8): 755-767, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37665569

RESUMO

The study developed and evaluated Sorafenib Tosylate (SRT)-loaded polymeric microparticles (MPs) using biodegradable polymer polycaprolactone (PCL) as a potential inhalable carrier for NSCLC. MPs were prepared by spray-drying an oil-in-water (o/w) emulsion. The optimized MPs demonstrated excellent flowability, particle size of 2.84 ± 0.5 µm, zeta potential of -14.0 ± 1.5 mV, and 85.08 ± 5.43% entrapment efficiency. ATR-FTIR/DSC studies revealed a lack of characteristic peaks of the crystalline drug signifying good entrapment of the drug. MPs were spherical and uniform in SEM pictures. The MPs showed a biphasic release pattern up to 72h. The Anderson cascade impactor (ACI) investigation demonstrated the highest drug deposition at stage 4, which revealed that the MPs can reach the lungs' secondary and terminal bronchi. Inhalable MPs had an efficient aerodynamic property with a mass median aerodynamic diameter (MMAD) of 2.63 ± 1.3 µm, a geometric standard deviation (GSD) of 1.93 ± 0.2 µm, and a fine particle fraction (FPF) of 87 ± 2.5%. Finally, in cytotoxicity studies on A549 cancer cells, MPs had an IC50 value of 0.6011 ± 0.8 µM, which was 85.68% lower than free drug. These findings suggest SRT-loaded inhalable PCL-based MPs as a novel NSCLC treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Células A549 , Sorafenibe/farmacologia , Poliésteres , Polímeros , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico
10.
Drug Discov Today ; 28(11): 103701, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37453459

RESUMO

Non-small cell lung cancer (NSCLC) has a long history of defying traditional cytotoxic treatment. Significant advancements in biotechnology, cancer biology, and immunotherapy have provided new insights that have altered the landscape for the management of NSCLC, clearing the way for a new era of pharmaceuticals in the form of monoclonal antibodies and their fragments. Antibody fragments are superior to monoclonal antibodies because of their small size, which allows them to penetrate cells and tissues effectively. When combined with functional nanocarriers, antibody fragments can target cancer cells while offering improved efficacy and fewer off-target effects. We discuss current topics of interest including anti-CTLA-4 mAbs, Talactoferrin alfa (TLF), and the CYFRA 21-1 biomarker, with brief insights into its novel detection system.


Assuntos
Antígenos de Neoplasias , Carcinoma Pulmonar de Células não Pequenas , Queratina-19 , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Imunoterapia , Fragmentos de Imunoglobulinas
11.
Expert Opin Drug Deliv ; 20(6): 773-783, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37086183

RESUMO

INTRODUCTION: Tranexamic acid is used for the treatment of hyperpigmentation, and the topical route is the most favorable route for its administration. Tranexamic acid lowers plasmin and tyrosinase, which reduces melanin and skin hyperpigmentation. Low penetration through the outer layer of skin and low availability at target melanocyte cells limit tranexamic acid topical administration. Different novel delivery systems like liposomes, microneedles, topical beads, and microparticles can help in overcoming these limitations. AREAS COVERED: The mechanism of action of tranexamic acid and novel delivery systems for its topical delivery have been discussed. Further, patents related to the topical delivery of tranexamic acid and clinical trials undertaken to analyze their potential have been discussed. EXPERT OPINION: Targeting tranexamic acid in the epidermal layer makes more amount of drug available for action on melanocytes, the target site for tranexamic acid. Novel drug delivery formulations like liposomes, solid lipid nanoparticles, nano-lipidic carriers, and topical beads have the potential of achieving epidermal targeting. Epidermal targeting of tranexamic acid can help in the superior delivery of the drug, making its topical treatment more efficient.


Assuntos
Hiperpigmentação , Ácido Tranexâmico , Humanos , Ácido Tranexâmico/uso terapêutico , Administração Cutânea , Lipossomos , Hiperpigmentação/tratamento farmacológico , Pele
12.
AAPS PharmSciTech ; 24(4): 101, 2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37038015

RESUMO

The present study was undertaken to synthesize PEGylated monomethoxy poly (ethylene glycol)-poly (ε-Caprolactone) (mPEG-PCL) block copolymer and formulate Erlotinib HCl-loaded mPEG-PCL nanoparticles for enhancing the bioavailability of the drug. Using the ring-opening polymerization technique, PEGylated mPEG-PCL block copolymer was synthesized, and the structure of the copolymer was characterized using FTIR, 1H-NMR, and DSC techniques. The solvent evaporation approach was used to effectively encapsulate Erlotinib HCl within block copolymeric nanoparticles. Erlotinib HCl-loaded mPEG-PCL nanoparticles had a mean particle size of 146.5 ± 2.37 nm and a zeta potential of -27.8 ± 2.77 mV. The nanoparticles had a percent entrapment efficiency of 80.78 ± 0.09%. The in vitro drug release of Erlotinib HCl-loaded copolymeric nanoparticles showed a slow and sustained release behavior which could be maintained for up to 72 h. The Korsmeyer-Peppas fitting findings indicated that the drug release process followed a non-Fickian diffusion mechanism. The pharmacokinetic (PK) behavior of the developed nanoformulation was studied in albino Wistar rats, and the relative bioavailability of the optimized NP formulation given by intravenous route was found to be 187.33%. The PK data suggested that Erlotinib HCl-loaded mPEG-PCL copolymeric nanoparticles can dramatically alter the PK behavior of Erlotinib HCl and greatly improve the drug's bioavailability by as much as three times when compared to the oral formulation. As a result, it was established that the block copolymeric nanoparticles have promise for the effective encapsulation of Erlotinib HCL for an injectable formulation with increased bioavailability.


Assuntos
Nanopartículas , Polietilenoglicóis , Ratos , Animais , Cloridrato de Erlotinib , Disponibilidade Biológica , Polietilenoglicóis/química , Poliésteres/química , Polímeros , Nanopartículas/química , Ratos Wistar , Tamanho da Partícula , Portadores de Fármacos/química
13.
3 Biotech ; 12(11): 301, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36276454

RESUMO

Glioblastoma multiforme (GBM) is one of the most lethal cancer due to poor diagnosis and rapid resistance developed towards the drug. Genes associated to cancer-related overexpression of proteins, enzymes, and receptors can be suppressed using an RNA silencing technique. This assists in obtaining tumour targetability, resulting in less harm caused to the surrounding healthy cells. RNA interference (RNAi) has scientific basis for providing potential therapeutic applications in improving GBM treatment. However, the therapeutic application of RNAi is challenging due to its poor permeability across blood-brain barrier (BBB). Nanobiotechnology has evolved the use of nanocarriers such as liposomes, polymeric nanoparticles, gold nanoparticles, dendrimers, quantum dots and other nanostructures in encasing the RNAi entities like siRNA and miRNA. The review highlights the role of these carriers in encasing siRNA and miRNA and promising therapy in delivering them to the glioma cells.

14.
J Control Release ; 350: 421-434, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36002053

RESUMO

Nanofibers are cutting-edge drug delivery systems that are being utilised to treat a variety of ailments. Nanofibers are mostly woven by electrospinning techniques that are majorly used in drug delivery, wound dressing, tissue engineering, sensors, etc. They have several limitations that can be addressed by developing nano-in-nano delivery techniques. Nanoparticles are incorporated into nanofibers in these nano-in-nano systems. They offer a lot of benefits over other nanosystems, including the ability to shield drugs from physical deterioration, the ability to provide prolonged drug release, high surface area to volume ratio, increased drug loading capacity and the potential to be employed in critical conditions such as cancer. These nanoparticles can be encapsulated, entrapped, or adsorbed onto nanofibers in a variety of ways. To include nanosystems into nanofibers, a variety of materials and different kinds of nanoparticles can be used. The present review gives an insight to the applications of nano - in - nano drug delivery system for different diseases/disorders. The review also brings forward the current state of these novel delivery systems along with future perspectives.


Assuntos
Nanofibras , Nanopartículas , Sistemas de Liberação de Medicamentos/métodos , Sistemas de Liberação de Fármacos por Nanopartículas , Preparações Farmacêuticas , Polímeros
15.
Curr Drug Deliv ; 19(2): 238-249, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33645480

RESUMO

PURPOSE: Gastric absorption is an upfront route for drug delivery as it is convenient, economical and most suitable for getting the desired systemic effects. Unfortunately, many traditional and newer generation drugs suffer from poor solubility and have lower bioavailability. With a perspective of bringing a novel delivery system in such a condition for old/existing/new drugs, liquidfilled hard capsules hold promise as the delivery system. METHODS: Anorganizedstate of the art literature review including patents was conducted to accommodate information on the innovations in technology, processes, and applications in the field of liquid filling in hard-shell capsules. RESULTS: The review findings revealed the importance of understanding the impact of liquid filled hard shell capsules would have in use of complex drug molecules, especially the ones sensitive to light and moisture. This technology can have diverse functions to be used for both immediate and delayed drug release. According to the technology point of view, the band sealing in such hardshell capsules helps in protecting against the tampering of capsule fill. CONCLUSION: The review provides an insight into the progression in the technology forefront related to formulation development of liquid formulations to be filled in hard shell capsules for better therapeutic potentials and convenience to the patients.


Assuntos
Química Farmacêutica , Gelatina , Cápsulas , Humanos , Solubilidade , Tecnologia Farmacêutica
16.
J Control Release ; 339: 51-74, 2021 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-34555491

RESUMO

Neglected tropical disease (NTD) is a set of 20 deadliest endemic diseases which shows its presence in most of the developing countries worldwide. Nearly 1 billion of the population are affected by it and suffered from poverty yearly. These diseases offer their own unique challenges and limitations towards effective prevention and treatment methods. Neglected tropical diseases are severe infections they may not kill the patient but debilitate the patient by causing severe skin deformities, disfigurement and horrible risks for several infections. Existing therapies for neglected diseases suffer from the loopholes like high degree of toxicity, side effects, low bioavailability, improper targeting and problematic application for affected populations. Progress in the field of nanotechnology in last decades suggested the intervention of nanocarriers to take over and drive the research and development to the next level by incorporating established drugs into the nanocarriers rather than discovering the newer drugs which is an expensive affair. These nanocarriers are believed to be a sure shot technique to fight infections at root level by virtue of its nanosize and ability to reach at cellular level. This article highlights the recent advances, rationale, targets and the challenges that are being faced to fight against NTDs and how the novel therapy tactics are able to contribute to its importance in prevention and treatment of NTDs.


Assuntos
Doenças Negligenciadas , Humanos , Doenças Negligenciadas/tratamento farmacológico
17.
J Control Release ; 336: 549-571, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34229001

RESUMO

Glioblastoma multiforme (GBM) is abnormal cell proliferation of glial cells. GBM is the grade IV glioma brain cancer which is life-threatening to many individuals affected by this cancer. The DNA alkylating agent Temozolomide (TMZ) has the distinctiveness of being FDA approved anticancer drug for the first line treatment for GBM. However, treatment of GBM still remains a challenge. This is attributed to TMZ's toxic nature, severe side effects, and fast degradation in vivo. In addition, the lack of targeting ability increases the chances of systemic toxicities. A nano enabled targeted delivery system not only improves the efficiency of TMZ by making it cross the blood brain barrier, have specificity to target, but also reduces toxicity to healthy tissues. Over the last decade the significant advances in the area of nanotechnology applied to medicine have developed many multifunctional therapeutics. In this context, the present review article comprehends the significant progress in the field of TMZ loaded nanocarriers showing promise for futuristic nanomedicine therapies in treating GBM.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Glioblastoma/tratamento farmacológico , Humanos , Temozolomida/uso terapêutico
18.
Curr Drug Deliv ; 18(9): 1338-1351, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33583375

RESUMO

BACKGROUND: Rifampicin is one of the first-line drugs used for tuberculosis therapy. The therapy lasts for a long time. Thus, there is a need to develop a sustained release formulation of rifampicin for intravenous application. AIM: This study is focused on preparing rifampicin-loaded bovine serum albumin nanoparticles (RIF BSA NPs) suitable for intravenous application using systematic quality by design (QbD) approach. OBJECTIVES: The main objective of this study is optimizing particle size and entrapment efficiency of rifampicin-loaded bovine serum albumin nanoparticles (RIF BSA NPs) and making them suitable for intravenous application using QbD approach. METHODS: Quality target product profile was defined along with critical quality attributes (CQAs) for the formulation. 32 factorial design was used for achieving the predetermined values of CQAs, i.e., mean particle size <200 nm and percent entrapment efficiency>50%. Incubation time of drug with colloidal albumin solution and ratio of rifampicin to albumin, were selected as independent variables. Checkpoint analysis was performed to confirm the suitability of the regression model for optimization. RESULTS: The optimized RIF BSA NPs were characterized by FTIR, DSC, 1H NMR techniques. The NPs observed by transmission electron microscopy were spherical in shape. The rifampicin release could be sustained for 72 hours from BSA NPs matrix. RIF BSA NPs dispersion was stable at 5 ± 3°C for 72 hours. Non-toxicity of nanoparticles to RAW 264.7 cell line was proved by MTT assay. CONCLUSION: Development of RIF BSA NPs with desired quality attributes was possible by implementing the QbD approach. The optimized formulation suitable for intravenous application can potentially improve the therapeutic benefits of rifampicin.


Assuntos
Nanopartículas , Soroalbumina Bovina , Portadores de Fármacos , Tamanho da Partícula , Rifampina
19.
Expert Opin Drug Deliv ; 18(1): 103-118, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33017541

RESUMO

INTRODUCTION: Nonsmall cell lung cancer (NSCLC) accounts for 80-85% of the cases of lung cancer. The conventional therapeutic effective dosage forms used to treat NSCLC are associated with rigid administration schedules, adverse effects, and may be associated with acquired resistance to therapy. Nanocarriers may provide a suitable alternative to regular formulations to overcome inherent drawbacks and provide better treatment modalities for the patient. AREAS COVERED: The article explores the application of drug loaded nanocarriers for lung cancer treatment. Drug-loaded nanocarriers can be modified to achieve controlled delivery at the desired tumor infested site. The type of nanocarriers employed are diverse based on polymers, liposomes, metals and a combination of two or more different base materials (hybrids). These may be designed for systemic delivery or local delivery to the lung compartment (via inhalation). EXPERT OPINION: Nanocarriers can improve pharmacokinetics of the drug payload by improving its delivery to the desired location and can reduce associated systemic toxicities. Through nanocarriers, a wide variety of therapeutics can be administered and targeted to the cancerous site. Some examples of the utilities of nanocarriers are codelivery of drugs, gene delivery, and delivery of other biologics. Overall, the nanocarriers have promising potential in improving therapeutic efficacy of drugs used in NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Nanopartículas , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Humanos , Lipossomos , Neoplasias Pulmonares/tratamento farmacológico
20.
Expert Opin Drug Deliv ; 18(1): 73-102, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32954834

RESUMO

INTRODUCTION: Non-small cell lung cancer (NSCLC) comprises of 84% of all lung cancer cases. The treatment options for NSCLC at advanced stages are chemotherapy and radiotherapy. Chemotherapy involves conventional nonspecific chemotherapeutics, and targeted-protein/receptor-specific small molecule inhibitors. Biologically targeted therapies such as an antibody-based immunotherapy have been approved in combination with conventional therapeutics. Approved targeted chemotherapy is directed against the kinase domains of mutated cellular receptors such as epidermal growth factor receptor (EGFR), anaplastic lymphoma kinases (ALK), neurotrophic receptor kinases (NTRK) and against downstream signaling molecules such as BRAF (v-raf murine sarcoma viral oncogene homolog B1). Approved biologically targeted therapy involves the use of anti-angiogenesis antibodies and antibodies against immune checkpoints. AREAS COVERED: The rationale for the employment of targeted therapeutics and the resistance that may develop to therapy are discussed. Novel targeted therapeutics in clinical trials are also included. EXPERT OPINION: Molecular and histological profiling of a given tumor specimen to determine the aberrant onco-driver is a must before deciding a targeted therapeutic regimen for the patient. Periodic monitoring of the patients response to a given therapeutic regimen is also mandatory so that any semblance of resistance to therapy can be deciphered and the regimen may be accordingly altered.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Imunoterapia , Neoplasias Pulmonares/tratamento farmacológico , Camundongos , Terapia de Alvo Molecular
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