RESUMEN

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.

Asunto(s)

Antineoplásicos , Nanotecnología , Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Antineoplásicos/química , Nanotecnología/métodos , Ponzoñas/administración & dosificación , Ponzoñas/uso terapéutico , Ponzoñas/farmacocinética , Ponzoñas/química , Péptidos/administración & dosificación , Péptidos/química , Sistemas de Liberación de Medicamentos/métodos , Nanopartículas/química , Portadores de Fármacos/química

RESUMEN

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.

Asunto(s)

Antineoplásicos , Neoplasias de la Mama , Gefitinib , Micelas , Poloxámero , Vitamina E , Humanos , Poloxámero/química , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Vitamina E/química , Femenino , Gefitinib/administración & dosificación , Gefitinib/farmacología , Gefitinib/química , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Antineoplásicos/farmacología , Simulación de Dinámica Molecular , Línea Celular Tumoral , Portadores de Fármacos/química , Simulación por Computador , Tamaño de la Partícula , Supervivencia Celular/efectos de los fármacos , Animales , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Polietilenglicoles/química , Liberación de Fármacos , Apoptosis/efectos de los fármacos

RESUMEN

Targeted drug delivery is an advanced approach for active targeting of tumor that can enhance the concentration of the drug at the site of action and reduce the off-target toxicity and non-specific effects of the drug. Folate receptors (FR) are membrane-bound surface proteins, over-expressed in numerous solid tumors, folate and folate conjugates bind to FR with higher affinity. In the present investigation, we fabricated Folic acid (FA) decorated Palbociclib loaded lipid-polymer hybrid nanoparticles (FA-PLPHNPs) using quality by design (QbD) approach and evaluated its anti-cancer activity in folate receptor-positive breast cancer cell lines. 1HNMR, ATR-FTIR spectroscopic techniques confirmed the formation of DSPE-PEG-FA ligand. The optimized FA-PLPHNPs formulation exhibited 143.36 ± 5.24 nm, 0.172 ± 0.004, -16.84 ± 0.27 mV, and 93.12 ± 0.43 % of particle size, PDI, zeta potential and % entrapment efficiency, respectively. The FA-PLPHNPs exhibited an approximately 9, 11-fold reduction in IC50 values than free Palbociclib in MCF-7 and MDA-MB-231 cells at 48 h. The role of FA in targeting breast cancer was studied by means of a receptor-blocking assay, and concluded that FA-PLPHNPs were internalized into MCF-7 and MDA-MB-231 cells by folate receptor-mediated endocytosis. FA-PLPHNPs showed higher anti-cancer efficiency and caused enhanced reactive oxygen species generation, apoptosis (Acridine orange/ ethidium bromide dual staining and Annexin V/PI staining), reduced cell migration, and colony formation. Thus, the fabricated Palbociclib-loaded FA-conjugated lipid polymer hybrid nanoparticles could act as a potential nanocarrier for the treatment of breast cancer.

Asunto(s)

Antineoplásicos , Neoplasias de la Mama , Nanopartículas , Humanos , Femenino , Polímeros/química , Neoplasias de la Mama/tratamiento farmacológico , Ácido Fólico/química , Sistemas de Liberación de Medicamentos/métodos , Apoptosis , Nanopartículas/química , Lípidos/farmacología , Línea Celular Tumoral , Portadores de Fármacos/química , Antineoplásicos/química

RESUMEN

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.

Asunto(s)

Neoplasias de la Mama , Compuestos Bicíclicos Heterocíclicos con Puentes , Nanopartículas , Sulfonamidas , Humanos , Femenino , Emulsiones , Sistemas de Liberación de Medicamentos , Solubilidad , Tensoactivos , Disponibilidad Biológica , Neoplasias de la Mama/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-bcl-2 , Administración Oral , Tamaño de la Partícula

RESUMEN

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.

Asunto(s)

Cromatografía de Fase Inversa , Piridinas , Ratas , Animales , Cromatografía Líquida de Alta Presión/métodos , Piperazinas/análisis

RESUMEN

Aim: This investigation aims to repurpose venetoclax using hyaluronic acid-coated venetoclax nanocrystals (HA-VEN-NCs) to target breast cancer. Materials & methods: An antisolvent precipitation method was used to fabricate the nanocrystals and optimize them using central composite design. Hyaluronic acid (HA)-coated and -uncoated nanocrystals were compared in terms of in vitro drug release, cell line studies, CD44-expressing breast tumor cell binding capability and anticancer activity. Results: HA-VEN-NCs and venetoclax nanocrystals (VEN-NCs) showed pH-responsive drug-release behavior, exhibiting sustained release at pH 6.8. Our extensive in vitro cell line investigation showed that HA-VEN-NCs efficiently bind to CD44-expressing breast tumor cells and possess excellent anticancer activity (IC50: 2.00 µg/ml) compared with VEN-NCs. Conclusion: Our findings anticipate that HA-VEN-NCs could serve as valuable nanoplatforms for cancer treatments in the future.

Asunto(s)

Antineoplásicos , Neoplasias de la Mama , Nanopartículas , Femenino , Humanos , Antineoplásicos/química , Neoplasias de la Mama/patología , Línea Celular Tumoral , Receptores de Hialuranos , Ácido Hialurónico/química , Nanopartículas/química

RESUMEN

Brinzolamide is an effective carbonic anhydrase inhibitor widely used in glaucoma therapy but limits its application due to inadequate aqueous solubility and permeability. The aim of the present research work is the development and characterization of brinzolamide-loaded ultradeformable bilosomes to enhance the corneal permeation of the drug. These ultradeformable bilosomes were prepared by ethanol injection method and evaluated for physicochemical properties, particle size, morphology, drug release, ultra-deformability, corneal permeation, and irritation potential. The optimized formulation exhibited an average particle size of 205.4 ± 2.04 nm with mono-dispersity (0.109 ± 0.002) and showed entrapment efficiency of 75.02 ± 0.017%, deformability index of 3.91, and release the drug in a sustained manner. The brinzolamide-loaded ultradeformable bilosomes released 76.29 ± 3.77% of the drug in 10 h that is 2.25 times higher than the free drug solution. The bilosomes were found non-irritant to eyes with a potential irritancy score of 0 in Hen's egg-chorioallantoic membrane assay. Brinzolamide-loaded ultradeformable bilosomes showed 83.09 ± 5.1% of permeation in 6 h and trans-corneal permeability of 8.78 ± 0.14 cm/h during the ex vivo permeation study. The acquired findings clearly revealed that the brinzolamide-loaded ultradeformable bilosomes show promising output and are useful in glaucoma therapy.

Asunto(s)

Inhibidores de Anhidrasa Carbónica , Glaucoma , Animales , Femenino , Inhibidores de Anhidrasa Carbónica/farmacología , Pollos , Córnea , Glaucoma/tratamiento farmacológico , Tamaño de la Partícula

RESUMEN

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.

Asunto(s)

Psoriasis , Masculino , Ratones , Animales , Imiquimod/efectos adversos , Piel , Inflamación/patología , Peso Corporal , Ratones Endogámicos BALB C , Modelos Animales de Enfermedad

RESUMEN

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.

Asunto(s)

Aceites Volátiles , Psoriasis , Aceite de Árbol de Té , Ratones , Animales , Aceites Volátiles/farmacología , Aceites Volátiles/metabolismo , Emulsiones/química , Piel/metabolismo , Psoriasis/metabolismo

RESUMEN

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.

Asunto(s)

Neoplasias de la Mama , Nanopartículas del Metal , Nanopartículas , Femenino , Humanos , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/tratamiento farmacológico , Nanopartículas/química , Nanotecnología , Polímeros/uso terapéutico , Portadores de Fármacos

RESUMEN

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.

Asunto(s)

Neoplasias Pulmonares , Micelas , Humanos , Línea Celular Tumoral , Polietilenglicoles , Polímeros , Tamaño de la Partícula , Proteínas Proto-Oncogénicas c-bcl-2 , Portadores de Fármacos , Vitamina E

RESUMEN

Poor aqueous solubility of drugs is still a foremost challenge in pharmaceutical product development. The use of lipids in designing formulations provides an opportunity to enhance the aqueous solubility and consequently bioavailability of drugs. Pre-dissolution of drugs in lipids, surfactants, or mixtures of lipid excipients and surfactants eliminate the dissolution/dissolving step, which is likely to be the rate-limiting factor for oral absorption of poorly water-soluble drugs. In this review, we exhaustively summarize the lipids excipients in relation to their classification, absorption mechanisms, and lipid-based product development. Methodologies utilized for the preparation of solid and semi-solid lipid formulations, applications, phase behaviour, and regulatory perspective of lipid excipients are discussed.

RESUMEN

Chondroitin Sulfate (CS) is an anionic hetero polysaccharide possessing anti-inflammatory, antioxidant, antitumor, anticoagulant and antithrombogenic activities. It is biodegradable and biocompatible in nature. Further, it inherits the ability of active and subcellular targeting due to its affinity for CD 44 receptors and glycosylation enzymes, which are overexpressed on the surface of tumor cells and intracellular organelles respectively. CS is known to degrade in presence of physiological stimuli, the hyaluronidase (HAase) enzyme and reactive oxygen species (ROS), assisting in site specific drug release. Due to these properties, it serve as a promising biomaterial for drug delivery and tissue engineering. In this review, the fundamental theory of CS, CS-based nanocarriers for the delivery of biopharmaceuticals and stimuli sensitive delivery systems such as HAase and ROS responsive nanocarriers for tumor targeted delivery are discussed critically. In addition, the manuscript describes the application of CS-based tissue constructs in tissue engineering and wound healing.

Asunto(s)

Productos Biológicos , Sulfatos de Condroitina , Materiales Biocompatibles/farmacología , Sistemas de Liberación de Medicamentos , Ingeniería de Tejidos

RESUMEN

Recently, microfabrication technology has been developed to increase the permeability of drugs for transdermal delivery. Microneedles are ultra-small needles usually in the micron size range (different dimensions in micron), generate pores, and allow for delivery of local medication in the systemic circulation via skin. The microneedles have been available in dissolving, solid, coated, hollow, and hydrogel-based microneedles. Dissolving microneedles have been fabricated using micro-molding, photo-polymerization, drawing lithography and droplet blowing techniques. Dissolving microneedles could be a valuable option for the delivery of low molecular weight drugs, peptides, enzymes, vaccines and bio-therapeutics. It consists of water-soluble materials including maltose, polyvinyl pyrrolidone, chondroitin sulfate, dextran, hyaluronic acid, and albumin. The microneedles have almost dissolved after patch removal, leaving only blunt stubs behind, which are easily removable. In this review, we summarize the major building blocks, classification, fabrication techniques, characterization, diffusion models and application of microneedles in diverse area. We also reviewed the regulatory aspects, computational studies, patents, clinical data, and market trends of microneedles.

Asunto(s)

Sistemas de Liberación de Medicamentos , Microinyecciones , Agujas , Administración Cutánea , Animales , Simulación por Computador , Humanos , Microtecnología

RESUMEN

The recent corona virus disease (COVID-19) outbreak has claimed the lives of many around the world and highlighted an urgent need for experimental strategies to prevent, treat and eradicate the virus. COVID-19, an infectious disease caused by a novel corona virus and no approved specific treatment is available yet. A vast number of promising antiviral treatments involving nanotechnology are currently under investigation to aid in the development of COVID-19 drug delivery. The prospective treatment options integrating the ever-expanding field of nanotechnology have been compiled, with the objective to show that these can be potentially developed for COVID-19 treatment. This review summarized the current state of knowledge, research priorities regarding the pandemic and post COVID-19. We also focus on the possible nanotechnology approaches that have proven to be successful against other viruses and the research agenda to combat COVID-19.

Asunto(s)

Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Animales , Antivirales/administración & dosificación , Betacoronavirus/aislamiento & purificación , COVID-19 , Infecciones por Coronavirus/fisiopatología , Infecciones por Coronavirus/virología , Sistemas de Liberación de Medicamentos , Desarrollo de Medicamentos/métodos , Humanos , Nanotecnología/métodos , Pandemias , Neumonía Viral/fisiopatología , Neumonía Viral/virología , SARS-CoV-2 , Tratamiento Farmacológico de COVID-19

RESUMEN

Polymer-drug conjugates (PDC) have exhibited clinical and commercial success in the field of drug delivery. A polymeric backbone, linker, targeting moiety, and drug constitute the building blocks of PDCs. Current attention is focusing on natural polymeric carriers, in particular the concept of graft copolymers, such as a combination of polymers and polysaccharides, to explore dual benefits such as combined vehicles and targeting moieties. Polymer heterogeneity, synthesis of PDCs, broad molecular weight distribution, conjugate variability, immunogenicity of polymers, safety, stability, and stringent regulatory approval are the major obstacles to the successful transition of PDCs to the clinic. In this review, we discuss natural and synthetic PDCs combined with computational modeling for diverse pharmaceutical and biomedical applications.

Asunto(s)

Portadores de Fármacos/administración & dosificación , Preparaciones Farmacéuticas/administración & dosificación , Polímeros/administración & dosificación , Animales , Simulación por Computador , Portadores de Fármacos/química , Humanos , Ligandos , Preparaciones Farmacéuticas/química , Polímeros/química

RESUMEN

The topical route is the most preferred one for administering drugs to eyes, skin and wounds for reaching enhanced efficacy and to improve patient compliance. Topical administration of drugs via conventional dosage forms such as solutions, creams and so forth to the eyes is associated with very low bioavailability (less than 5%) and hence, we cannot rely on these for delivering drugs to eyes more efficiently. An intravitreal injection is another popular drug delivery regime but is associated with complications like intravitreal hemorrhage, retinal detachment, endophthalmitis, and cataracts. The skin has a complex structure that serves as numerous physiological barriers to the entry of exogenous substances. Drug localization is an important aspect of some dermal diseases and requires directed delivery of the active substance to the diseased cells, which is challenging with current approaches. Existing therapies used for wound healing are costly, and they involve long-lasting treatments with 70% chance of recurrence of ulcers. Nanotechnology is a novel and highly potential technology for designing formulations that would improve the efficiency of delivering drugs via the topical route. This review involves a discussion about how nanotechnology-driven drug delivery systems have evolved, and their potential in overcoming the natural barriers for delivering drugs to eyes, skin and wounds.