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1.
Expert Opin Drug Deliv ; 21(8): 1213-1233, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39136542

RESUMO

INTRODUCTION: Skin carcinoma, including malignant melanoma, basal, squamous, and Merkel cell carcinoma, present significant healthcare challenges. Conventional treatments like surgery and chemotherapy suffer from limitations like non-specificity, toxicity, and adverse effects. The upcoming treatments are dominated by nano-sized delivery systems, which improve treatment outcomes while minimizing side effects. Moving ahead, targeted nanoparticles allow localized delivery of drugs at tumor site, ensuring minimal damage to surrounding tissues. AREAS COVERED: This review explores various targeting strategies for specific types of skin cancers. The strategies discussed include nanocarrier-mediated targeted delivery with multiple types of ligands like aptamers, antibodies, peptides, and vitamins and their advantages in skin cancer. Upcoming cutting-edge technologies such as smart delivery systems, microneedle-assisted delivery and three-dimensional printed scaffolds have also been discussed in detail. The findings in this review are summarized from databases like PubMed, Scopus, Web of Science, ClinicalTrials.gov, NIH, and articles published between 2005 and 2024 that discuss targeted therapy for skin cancer. EXPERT OPINION: Specific cancer-targeting strategies promise personalized treatments, improving response rates and reducing need for intensive therapies. The review highlights various challenges, their solution, and economic aspects in this dynamic field. It further emphasizes the potential for specialized strategies to revolutionize skin cancer treatment.


Assuntos
Antineoplásicos , Sistemas de Liberação de Medicamentos , Neoplasias Cutâneas , Humanos , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Melanoma/tratamento farmacológico , Terapia de Alvo Molecular , Sistemas de Liberação de Fármacos por Nanopartículas/química , Nanopartículas , Medicina de Precisão , Neoplasias Cutâneas/tratamento farmacológico
2.
Expert Opin Ther Targets ; 28(8): 689-700, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39086205

RESUMO

INTRODUCTION: Psoriasis is a chronic immune-mediated disorder affecting over 2-3% of the population worldwide, significantly impacting quality of life. Despite the availability of various therapeutic interventions, concerns persist regarding lesion recurrence and potential alterations in immune surveillance promoting cancer progression. Recent advancements in understanding cellular and molecular pathways have unveiled key factors in psoriasis etiology, including IL-17, 22, 23, TNF-α, PDE-4, JAK-STAT inhibitors, and AhR agonists. This work explores the potential of S-phase kinase-associated protein 2 (Skp2) as a therapeutic target in psoriasis. AREA COVERED: This review covers the current understanding of psoriasis pathophysiology, including immune dysregulation, and the role of keratinocytes and ubiquitin. It also delves into Skp2 role in cell cycle regulation, and its correlation with angiogenesis and ubiquitin in psoriasis. The evolving therapeutic approaches targeting Skp2, including small molecule inhibitors, are also discussed. EXPERT OPINION: Targeting Skp2 holds promise for developing novel therapeutic approaches for psoriasis. By modulating Skp2 activity or expression, it may be possible to intervene in inflammatory and proliferative processes underlying the disease. Further research into Skp2 inhibitors and their efficacy in preclinical and clinical settings is warranted to harness the full potential of Skp2 as a therapeutic target in psoriasis management.


Assuntos
Terapia de Alvo Molecular , Psoríase , Proteínas Quinases Associadas a Fase S , Humanos , Proteínas Quinases Associadas a Fase S/antagonistas & inibidores , Proteínas Quinases Associadas a Fase S/metabolismo , Psoríase/tratamento farmacológico , Psoríase/patologia , Animais , Qualidade de Vida , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Ubiquitina/metabolismo , Desenvolvimento de Medicamentos
3.
RSC Adv ; 14(30): 21915-21937, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38989245

RESUMO

Skin carcinoma is one of the most prevalent types of carcinomas. Due to high incidence of side effects in conventional therapies (radiotherapy and chemotherapy), photodynamic therapy (PDT) has gained huge attention as an alternate treatment strategy. PDT involves the administration of photosensitizers (PS) to carcinoma cells which produce reactive oxygen species (ROS) on irradiation by specific wavelengths of light that result in cancer cells' death via apoptosis, autophagy, or necrosis. Topical delivery of PS to the skin cancer cells at the required concentration is a challenge due to the compounds' innate physicochemical characteristics. Nanocarriers have been observed to improve skin permeability and enhance the therapeutic efficiency of PDT. Polymeric nanoparticles (NPs), metallic NPs, and lipid nanocarriers have been reported to carry PS successfully with minimal side effects and high effectiveness in both melanoma and non-melanoma skin cancers. Advanced carriers such as quantum dots, microneedles, and cubosomes have also been addressed with reported studies to show their scope of use in PDT-assisted skin cancer treatment. In this review, nanocarrier-aided PDT in skin cancer therapies has been discussed with clinical trials and patents. Additionally, novel nanocarriers that are being investigated in PDT are also covered with their future prospects in skin carcinoma treatment.

4.
Anal Methods ; 16(24): 3847-3858, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38841864

RESUMO

AKBA (3-acetyl-11-keto-ß-boswellic acid) is a phytoconstituent derived from Boswellia serrata extract and utilized in the management of rheumatoid arthritis. Drug delivery approaches showed interest in delivering AKBA with advanced nanotechnology. There is a need for a simple, sensitive, and robust HPLC method that can determine AKBA in complex nanoformulation and in vitro and ex vivo samples. In the proposed work, the RP-HPLC method was developed using a mobile phase comprising a mixture of acetonitrile : milli Q (90 : 10) at detection λmax 250 nm. The method exhibited a linearity of 250 to 20 000 ng mL-1 with a high correlation coefficient of 1. The limit of detection and limit of quantification for the analytes were found to be 41.32 ng mL-1 and 125.21 ng mL-1, respectively. In the accuracy study, the % recovery of AKBA was found to be 98% to 102%, and the precision study showed less than 2% relative standard deviation. The developed method was found to be robust under chromatographic conditions with changes in pH and mobile phase mixture ratio. The method was also explored for forced degradation study, and the results showed the successful separation of degradation products from the AKBA. Further, the RP-HPLC method was applied for the quantification of AKBA in topical nanoformulations and different matrices, such as skin matrices and adhesive tapes. The method was able to measure entrapment efficiency (93.13 ± 1.94%), drug loading (25.83 ± 0.54%), drug assay in a gel matrix (96.99 ± 3.89%), drug amount in stratum corneum (7.90 ± 0.62 µg cm-2), and drug amount in viable skin layers (33.94 ± 0.21 µg cm-2) with high-speed reproducibility. The developed method can be utilized for the routine analysis of AKBA in conventional and complex formulations in academia and industry.


Assuntos
Triterpenos , Triterpenos/análise , Cromatografia Líquida de Alta Pressão/métodos , Animais , Cromatografia de Fase Reversa/métodos , Pele/química , Pele/metabolismo , Limite de Detecção , Reprodutibilidade dos Testes , Boswellia/química , Suínos , Humanos
5.
Int J Biol Macromol ; 271(Pt 1): 132586, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38795889

RESUMO

Rheumatoid Arthritis (RA) is a chronic, inflammatory, auto-immune disease that is majorly associated with the degradation of the synovial linings of the joints. It is a progressive disease that reduces the life span in affected individuals. Nanoparticles involving hyaluronic acid (HA) have gained the limelight for designing target-specific and more effective drug delivery options for RA. HA is found abundantly in the synovial fluid and acts as a natural ligand for the CD44 receptors. The targeted delivery approach using CD44 as the target can help in minimizing off-target drug distribution. These HA-based surface-decorated nanocarriers, hydrogels, and MNs are cutting-edge strategies that promise tailored delivery, fewer side effects, and more patient adherence to address the common issues associated with RA therapy. Considering the above facts, this review attempts to discuss the role of HA in making more effective formulations for therapeutic delivery in treating RA. Additionally, it provides a comprehensive overview of the potential advancements, mainly in treating RA by HA-based topical, transdermal, and parenteral drug delivery systems, with relevant case studies. The existing difficulties and potential paths for future research on HA-based non-conventional formulations for the management of RA are also discussed.


Assuntos
Artrite Reumatoide , Sistemas de Liberação de Medicamentos , Ácido Hialurônico , Ácido Hialurônico/química , Artrite Reumatoide/tratamento farmacológico , Humanos , Sistemas de Liberação de Medicamentos/métodos , Animais , Portadores de Fármacos/química , Nanopartículas/química , Antirreumáticos/administração & dosagem , Antirreumáticos/uso terapêutico , Antirreumáticos/farmacocinética , Antirreumáticos/química , Receptores de Hialuronatos/metabolismo
6.
Mol Pharm ; 21(4): 1591-1608, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38396330

RESUMO

The perpetuity of cancer prevalence at a global level calls for development of novel therapeutic approaches with improved targetability and reduced adverse effects. Conventional cancer treatments have a multitude of limitations such as nonselectivity, invasive nature, and severe adverse effects. Chemotherapy is also losing its efficacy because of the development of multidrug resistance in the majority of cancers. To address these issues, selective targeting-based approaches are being explored for an effective cancer treatment. Mitochondria, being the moderator of a majority of crucial cellular pathways like metabolism, apoptosis, and reactive oxygen species (ROS) homeostasis, are an effective targeting site. Mitochondria-targeted photodynamic therapy (PDT) has arisen as a potential approach in this endeavor. By designing photosensitizers (PSs) that preferentially accumulate in the mitochondria, PDT offers a localized technique to induce cytotoxicity in cancer cells. In this review, we intend to explore the crucial principles and challenges associated with mitochondria-targeted PDT, including variability in mitochondrial function, mitochondria-specific PSs, targeted nanocarrier-based monotherapy, and combination therapies. The hurdles faced by this emerging strategy with respect to safety, optimization, clinical translation, and scalability are also discussed. Nonetheless, mitochondria-targeted PDT exhibits a significant capacity in cancer treatment, especially in combination with other therapeutic modalities. With perpetual research and technological advancements, this treatment strategy is a great addition to the arsenal of cancer treatment options, providing better tumor targetability while reducing the damage to surrounding healthy tissues. This review emphasizes the current status of mitochondria-targeted PDT, limitations, and future prospects in its pursuit of safe and efficacious cancer therapy.


Assuntos
Neoplasias , Fotoquimioterapia , Fotoquimioterapia/métodos , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Apoptose , Mitocôndrias , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo
7.
Carbohydr Polym ; 327: 121655, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38171676

RESUMO

Wound dressings act as a physical barrier between the wound site and the external environment, preventing additional harm; choosing suitable wound dressings is essential for the healing process. Polysaccharide biopolymers have demonstrated encouraging findings and therapeutic prospects in recent decades about wound therapy. Additionally, polysaccharides have bioactive qualities like anti-inflammatory, antibacterial, and antioxidant capabilities that can help the process of healing. Due to their excellent tissue adhesion, swelling, water absorption, bactericidal, and immune-regulating properties, polysaccharide-based bio-adhesive films have recently been investigated as intriguing alternatives in wound management. These films also mimic the structure of the skin and stimulate the regeneration of the skin. This review presented several design standards and functions of suitable bio-adhesive films for the healing of wounds. Additionally, the most recent developments in the use of bio-adhesive films as wound dressings based on polysaccharides, including hyaluronic acid, chondroitin sulfate, dextran, alginate, chitosan, cellulose, konjac glucomannan, gellan gum, xanthan gum, pectin, guar gum, heparin, arabinogalactans, carrageen, and tragacanth gum, are thoroughly discussed. Lastly, to create a road map for the function of polysaccharide-based bio-adhesive films in advanced wound care, their clinical performances and future challenges in making bio-adhesive films by three-dimensional bioprinting are summarized.


Assuntos
Adesivos , Polissacarídeos , Polissacarídeos/química , Cicatrização , Bandagens , Alginatos/química , Antibacterianos/farmacologia
8.
Int J Biol Macromol ; 256(Pt 1): 128348, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38007021

RESUMO

Hydrogels are a versatile category of biomaterials that have been widely applied in the fields of biomedicine for the last several decades. The three-dimensional polymeric crosslinked hydrophilic structures of the hydrogel can proficiently hold drugs, nanoparticles, and cells, making them a potential delivery system. However, disadvantages like low mechanical strength, poor biocompatibility, and unusual in-vivo biodegradation are associated with conventional hydrogels. To overcome these hurdles, hybrid hydrogels are designed using two or more structurally different polymeric units. Polysaccharides, characterized by their innate biocompatibility, biodegradability, and abundance, establish an ideal foundation for the development of these hybrid hydrogels. This review aims to discuss the studies that have utilized naturally occurring polysaccharides to prepare hybrid systems, which were aimed for various biomedical applications such as tissue engineering, bone and cartilage regeneration, wound healing, skin cancer treatment, antimicrobial therapy, osteoarthritis treatment, and drug delivery. Furthermore, this review extensively examines the properties of the employed polysaccharides within hydrogel matrices, emphasizing the advantageous characteristics that make them a preferred choice. Furthermore, the challenges associated with the commercial implementation of these systems are explored alongside an assessment of the current patent landscape.


Assuntos
Hidrogéis , Polissacarídeos , Hidrogéis/química , Polissacarídeos/química , Materiais Biocompatíveis/química , Engenharia Tecidual/métodos , Sistemas de Liberação de Medicamentos , Polímeros
9.
Expert Opin Ther Targets ; 27(12): 1247-1256, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37997278

RESUMO

INTRODUCTION: Psoriasis is a chronic, inflammatory, non-communicable skin disorder that affects a patient's social and emotional well-being. It is characterized by hyperproliferation of keratinocytes, irregular shedding of skin cells, and abnormal invasion of inflammatory mediators. The treatment strategy is designed based on the severity of the disease condition starting from topical, phototherapy, systemic, and biologics. In recent years, extensive research into the underlying mechanisms of psoriasis has led to significant advancement in treatment options from small molecules to biologics. AREA COVERED: This review focuses on intracellular and molecular mechanisms such as AhR, A3AR, RIP1, CGRP, and S1P that serve as novel pharmacological targets for psoriasis. Moreover, new molecules are approved or are under clinical investigation to interfere with these target mechanisms. EXPERT OPINION: A detailed understanding of signaling pathways provides potential targets and molecular mechanisms for the inflammatory cascade in psoriasis. This has led to the development of small molecules targeting specific pathways. Further, the combination of nanotechnology can assist in dose reduction leading to reduced adverse effects in the management of psoriasis.


Assuntos
Produtos Biológicos , Psoríase , Humanos , Psoríase/tratamento farmacológico , Psoríase/metabolismo , Pele/metabolismo , Produtos Biológicos/metabolismo , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico
11.
AAPS PharmSciTech ; 24(7): 188, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37715004

RESUMO

Hydroxypropyl methylcellulose acetate succinate (HPMCAS) has multi-disciplinary applications spanning across the development of drug delivery systems, in 3D printing, and in tissue engineering, etc. HPMCAS helps in maintaining the drug in a super-saturated condition by inhibiting its precipitation, thereby increasing the rate and extent of dissolution in the aqueous media. HPMCAS has several distinctive characteristics, such as being amphiphilic in nature, having an ionization pH, and a succinyl and acetyl substitution ratio, all of which are beneficial while developing formulations. This review provides insights regarding the various types of formulations being developed using HPMCAS, including amorphous solid dispersion (ASD), amorphous nanoparticles, dry coating, and 3D printing, along with their applicability in drug delivery and biomedical fields. Furthermore, HPMCAS, compared with other carbohydrate polymers, shows several benefits in drug delivery, including proficiency in imparting stable ASD with a high dissolution rate, being easily processable, and enhancing bioavailability. The various commercially available formulations, regulatory considerations, and key patents containing the HPMCAS have been discussed in this review.


Assuntos
Metilcelulose , Nanopartículas , Sistemas de Liberação de Medicamentos , Disponibilidade Biológica
12.
ACS Omega ; 8(21): 18340-18357, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37273582

RESUMO

Nanotechnology has yielded nanostructure-based drug delivery approaches, among which nanofibers have been explored and researched for the potential topical delivery of therapeutics. Nanofibers are filaments or thread-like structures in the nanometer size range that are fabricated using various polymers, such as natural or synthetic polymers or their combination. The size or diameter of the nanofibers depends upon the polymers, the techniques of preparation, and the design specification. The four major processing techniques, phase separation, self-assembly, template synthesis, and electrospinning, are most commonly used for the fabrication of nanofibers. Nanofibers have a unique structure that needs a multimethod approach to study their morphology and characterization parameters. They are gaining attention as drug delivery carriers, and the substantially vast surface area of the skin makes it a potentially promising strategy for topical drug products for various skin disorders such as psoriasis, skin cancers, skin wounds, bacterial and fungal infections, etc. However, the large-scale production of nanofibers with desired properties remains challenging, as the widely used electrospinning processes have certain limitations, such as poor yield, use of high voltage, and difficulty in achieving in situ nanofiber deposition on various substrates. This review highlights the insights into fabrication strategies, applications, recent clinical trials, and patents of nanofibers for different skin disorders in detail. Additionally, it discusses case studies of its effective utilization in the treatment of various skin disorders for a better understanding for readers.

13.
Mol Pharm ; 20(7): 3653-3671, 2023 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-37262335

RESUMO

Topical administration of anti-cancer drugs along with photodynamically active molecules is a non-invasive approach, which stands to be a promising modality for treating aggressive cutaneous melanomas with the added advantage of high patient compliance. However, the efficiency of delivering drugs topically is limited by several factors, such as penetration of the drug across skin layers at the tumor site and limited light penetrability. In this study, curcumin, an active anti-cancer agent, and chlorin e6, a photoactivable molecule, were encapsulated into lipidic nanoparticles that produced reactive oxygen species (ROS) when activated at 665 nm by near-infrared (NIR) light. The optimized lipidic nanoparticle containing curcumin and chlorin e6 exhibited a particle size of less than 100 nm. The entrapment efficiency for both molecules was found to be 81%. The therapeutic efficacy of the developed formulation was tested on B16F10 and A431 cell lines via cytotoxicity evaluation, combination index, cellular uptake, nuclear staining, DNA fragmentation, ROS generation, apoptosis, and cell cycle assays under NIR irradiation (665 nm). Co-delivering curcumin and chlorin e6 exhibited higher cellular uptake, better cancer growth inhibition, and pronounced apoptotic events compared to the formulation having the free drug alone. The study results depicted that topical application of this ROS-generating dual-drug-loaded lipidic nanoparticles incorporated in SEPINEO gel achieved better permeation (80 ± 2.45%) across the skin, and exhibited the improved skin retention and a synergistic effect as well. The present work introduces photo-triggered ROS-generating dual-drug-based lipidic nanoparticles, which are simple and efficient to develop and exhibit synergistic therapeutic effects against cutaneous melanoma.


Assuntos
Curcumina , Melanoma , Nanopartículas , Fotoquimioterapia , Neoplasias Cutâneas , Humanos , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Nanopartículas/uso terapêutico , Lipídeos , Linhagem Celular Tumoral , Melanoma Maligno Cutâneo
14.
Biomed Pharmacother ; 162: 114634, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37018989

RESUMO

The present work aimed to prepare and evaluate Apremilast loaded lyotropic liquid crystalline nanoparticles (LCNPs) formulation for skin delivery to enhance the efficacy with reduced adverse effects of the oral therapy in psoriasis treatment. The LCNPs were prepared using the emulsification using a high shear homogenizer for size reduction and optimized with Box Behnken design to achieve desired particle size and entrapment efficiency. The selected LCNPs formulation was evaluated for in-vitro release, in-vitro psoriasis efficacy, skin retention, dermatokinetic, in-vivo skin retention, and skin irritation study. The selected formulation exhibited 173.25 ± 2.192 nm (polydispersity 0.273 ± 0.008) particle size and 75.028 ± 0.235% entrapment efficiency. The in-vitro drug release showed the prolonged-release for 18 h. The ex-vivo studies revealed that LCNPs formulation exhibited drug retention up to 3.2 and 11.9-fold higher, in stratum corneum and viable epidermis compared to conventional gel preparation. In-vitro cell line studies performed on immortal keratinocyte cells (HaCaT cells) demonstrated non-toxicity of selected excipients used in designed LCNPs. The dermatokinetic study revealed the AUC0-24 of the LCNPs loaded gel was 8.4 fold higher in epidermis and 2.06 fold in dermis, respectively compared to plain gel. Further, in-vivo animal studies showed enhanced skin permeation and retention of Apremilast compared to conventional gel.


Assuntos
Nanopartículas , Psoríase , Animais , Hidrogéis/farmacologia , Portadores de Fármacos/química , Pele , Psoríase/tratamento farmacológico , Nanopartículas/química , Tamanho da Partícula
15.
Pharmaceutics ; 15(3)2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36986597

RESUMO

The current study aimed to develop a topical emulgel of dasatinib (DTB) for rheumatoid arthritis (RA) treatment to reduce systemic side effects. The quality by design (QbD) approach was employed to optimize DTB-loaded nano-emulgel using a central composite design (CCD). Emulgel was prepared using the hot emulsification method, and then the particle size (PS) was reduced using the homogenization technique. The PS and % entrapment efficiency (% EE) were found to be 172.53 ± 3.33 nm (0.160 ± 0.014 PDI) and 95.11 ± 0.16%, respectively. The nano-emulsion (CF018 emulsion) in vitro drug release profile showed sustained release (SR) up to 24 h. MTT assay results from an in vitro cell line study revealed that formulation excipients had no effect, whereas emulgel showed a high degree of internalization. Furthermore, emulgel treatment significantly reduced LPS-induced TNF-α production in RAW 264.7 cells. The spherical shape was depicted in FESEM images of optimized nano-emulgel (CF018 emulgel) formulation. Ex vivo skin permeation was significantly increased when compared to the free drug-loaded gel (FDG). In vivo data revealed that the optimized CF018 emulgel is a non-irritant and is safe. In terms of paw swelling, the FCA-induced arthritis model demonstrated that the CF018 emulgel reduced paw swelling percentage compared to adjuvant-induced arthritis (AIA) control group. Following clinical testing in the near future, the designed preparation could be a viable alternative treatment for RA.

16.
Expert Opin Drug Deliv ; 20(6): 721-738, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36893450

RESUMO

INTRODUCTION: For decades, finding effective long-term or disease-modifying treatments for skin disorders has been a major focus of scientists. The conventional drug delivery systems showed poor efficacy with high doses and are associated with side effects, which lead to challenges in adherence to therapy. Therefore, to overcome the limitations of conventional drug delivery systems, drug delivery research has focused on topical, transdermal, and intradermal drug delivery systems. Among all, the dissolving microneedles have gained attention with a new range of advantages of drug delivery in skin disorders such as breaching skin barriers with minimal discomfort and its simplicity of application to the skin, which allows patients to administer it themselves. AREAS COVERED: This review highlighted the insights into dissolving microneedles for different skin disorders in detail. Additionally, it also provides evidence for its effective utilization in the treatment of various skin disorders. The clinical trial status and patents for dissolving microneedles for the management of skin disorders are also covered. EXPERT OPINION: The current review on dissolving microneedles for skin drug delivery is accentuating the breakthroughs achieved so far in the management of skin disorders. The output of the discussed case studies anticipated that dissolving microneedles can be a novel drug delivery strategy for the long-term treatment of skin disorders.


Assuntos
Agulhas , Dermatopatias , Humanos , Microinjeções , Pele , Administração Cutânea , Sistemas de Liberação de Medicamentos , Dermatopatias/tratamento farmacológico
17.
Eur J Pharm Biopharm ; 186: 18-29, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36924995

RESUMO

Temozolomide (TMZ) is one of the best choices for treating glioblastoma. However, due to the short plasma half-life, only 20-30 % brain bioavailability can be achieved using traditional formulations. In the present study, PEGylated liposomes and lyotropic liquid crystals (LLCs) were developed and investigated to prolong the plasma circulation time of TMZ. Industrially feasible membrane extrusion and modified hot melt emulsification techniques were utilized during the formulation. Liposomes and LLCs in the particle size range of 80-120 nm were obtained with up to 50 % entrapment efficiency. The nanocarriers were found to show a prolonged release of up to 72 h. The cytotoxicity studies in glioblastoma cell lines revealed a âˆ¼1.6-fold increased cytotoxicity compared to free TMZ. PEGylated liposomes and PEGylated LLCs were found to show a 3.47 and 3.18-fold less cell uptake in macrophage cell lines than uncoated liposomes and LLCs, respectively. A 1.25 and 2-fold increase in the plasma t1/2 was observed with PEGylated liposomes and PEGylated LLCs, respectively, compared to the TMZ when administered intravenously. Extending plasma circulation time of TMZ led to significant increase in brain bioavailability. Overall, the observed improved pharmacokinetics and biodistribution of TMZ revealed the potential of these PEGylated nanocarriers in the efficient treatment of glioblastoma.


Assuntos
Lipossomos , Temozolomida , Temozolomida/administração & dosagem , Temozolomida/efeitos adversos , Temozolomida/farmacocinética , Cristais Líquidos , Polietilenoglicóis , Humanos , Meia-Vida , Glioblastoma/tratamento farmacológico , Neoplasias Encefálicas/tratamento farmacológico , Distribuição Tecidual , Barreira Hematoencefálica/metabolismo , Sistemas de Liberação de Fármacos por Nanopartículas , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Alquilantes/farmacocinética , Masculino , Animais , Ratos
18.
Eur J Pharm Biopharm ; 186: 43-54, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36940886

RESUMO

Long-term oral tofacitinib (TOF) administration has been linked to serious side effects majorly immunological suppression. The aim of this work was to enhance the therapeutic efficacy of TOF by chondroitin sulphate (CS) coated proglycosomes through the anchoring of high-affinity CS to CD44 receptors on immune cells in the inflammatory region. The CS was coated onto the TOF-loaded proglycosomes (CS-TOF-PG) formulations and they were evaluated for in vitro drug release, ex vivo (permeation, dermatokinetics) studies. In vivo efficacy studies were carried out in Freund's complete adjuvant (CFA) induced arthritis model. The optimized CS-TOF-PG showed particle sizes of 181.13 ± 7.21 nm with an entrapment efficiency of 78.85 ± 3.65 %. Ex-vivo studies of CS-TOF-PG gel exhibited 1.5-fold high flux and 1.4-fold dermal retention compared to FD-gel. The efficacy study revealed that CS-TOF-PG showed a significant (P < 0.001) reduction in inflammation in arthritic rat paws compared to the TOF oral and FD gel. The current study ensured that the CS-TOF-PG topical gel system would provide a safe and effective formulation for localization and site-specific delivery of TOF at the RA site and overcome the adverse effects associated with the TOF.


Assuntos
Artrite Experimental , Artrite Reumatoide , Ratos , Animais , Sulfatos de Condroitina , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Piperidinas
19.
ACS Omega ; 8(1): 74-86, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36643539

RESUMO

Nanocarriers have the utmost significance for advancements in drug delivery and nanomedicine technology. They are classified as polymer-based nanocarriers, lipid-based nanocarriers, viral nanoparticles, or inorganic nanoparticles, depending on their constituent parts. Lipid-based nanocarrier systems have gained tremendous attention over the years because of their noteworthy properties like high drug-loading capacity, lower toxicity, better bioavailability and biocompatibility, stability in the gastrointestinal tract, controlled release, simpler scale-up, and validation process. Nanocarriers still have some disadvantages like poor drug penetration, limited drug encapsulation, and poor targeting. These disadvantages can be overcome by their surface modification. Surface-modified nanocarriers result in controlled release, enhanced penetration efficiency, and targeted medication delivery. In this review, the authors summarize the numerous lipid-based nanocarriers and their functionalization through various surface modifiers such as polymers, ligands, surfactants, and fatty acids. Recent examples of newly developing surface-modified lipid-based nanocarrier systems from the available literature, along with their applications, have been compiled in this work.

20.
Pharmaceutics ; 15(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36678794

RESUMO

Nano-emulgel is an emerging drug delivery system intended to enhance the therapeutic profile of lipophilic drugs. Lipophilic formulations have a variety of limitations, which includes poor solubility, unpredictable absorption, and low oral bioavailability. Nano-emulgel, an amalgamated preparation of different systems aims to deal with these limitations. The novel system prepared by the incorporation of nano-emulsion into gel improves stability and enables drug delivery for both immediate and controlled release. The focus on nano-emulgel has also increased due to its ability to achieve targeted delivery, ease of application, absence of gastrointestinal degradation or the first pass metabolism, and safety profile. This review focuses on the formulation components of nano-emulgel for topical drug delivery, pharmacokinetics and safety profiles.

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