Dendrimer: An update on recent developments and future opportunities for the brain tumors diagnosis and treatment.

A brain tumor is an uncontrolled cell proliferation, a mass of tissue composed of cells that grow and divide abnormally and appear to be uncontrollable by the processes that normally control normal cells. Approximately 25,690 primary malignant brain tumors are discovered each year, 70% of which originate in glial cells. It has been observed that the blood-brain barrier (BBB) limits the distribution of drugs into the tumour environment, which complicates the oncological therapy of malignant brain tumours. Numerous studies have found that nanocarriers have demonstrated significant therapeutic efficacy in brain diseases. This review, based on a non-systematic search of the existing literature, provides an update on the existing knowledge of the types of dendrimers, synthesis methods, and mechanisms of action in relation to brain tumours. It also discusses the use of dendrimers in the diagnosis and treatment of brain tumours and the future possibilities of dendrimers. Dendrimers are of particular interest in the diagnosis and treatment of brain tumours because they can transport biochemical agents across the BBB to the tumour and into the brain after systemic administration. Dendrimers are being used to develop novel therapeutics such as prolonged release of drugs, immunotherapy, and antineoplastic effects. The use of PAMAM, PPI, PLL and surface engineered dendrimers has proven revolutionary in the effective diagnosis and treatment of brain tumours.

Enhanced skin penetration of Finasteride loaded DMSO-liposomes for the treatment of androgenic alopecia: comparison with conventional liposomes.

Long-term treatment with finasteride (FIN) for androgenic alopecia is restricted due to its systemic side effects. To address this problem, DMSO-modified liposomes were prepared in the present study to improve the topical delivery of FIN. DMSO-liposomes were prepared by a modification of the ethanol injection method. It was hypothesized that the permeation-enhancing property of DMSO could promote drug delivery to deeper skin layer where hair follicles are present. Liposomes were optimized by quality by design (QbD) approach and biologically evaluated in a rat model of testosterone-induced alopecia. Optimized DMSO-liposomes were spherical and had mean vesicle size, zeta potential, and entrapment efficiency of 330.1 ± 1.5, -14.52 ± 1.32, and 59.02 ± 1.12%, respectively. Biological evaluation on testosterone-induced alopecia and skin histology shows that follicular density and anagen/telogen (A/T) ratio were increased in rats treated with DMSO-liposomes as compared to FIN-liposomes without DMSO and an alcoholic solution of FIN applied topically. DMSO-liposomes could be promising skin delivery vehicles for FIN or similar drugs.

Recent Advances in Cancer Vaccines: Challenges, Achievements, and Futuristic Prospects.

Cancer is a chronic disease, and it can be lethal due to limited therapeutic options. The conventional treatment options for cancer have numerous challenges, such as a low blood circulation time as well as poor solubility of anticancer drugs. Therapeutic cancer vaccines emerged to try to improve anticancer drugs' efficiency and to deliver them to the target site. Cancer vaccines are considered a viable therapeutic technique for most solid tumors. Vaccines boost antitumor immunity by delivering tumor antigens, nucleic acids, entire cells, and peptides. Cancer vaccines are designed to induce long-term antitumor memory, causing tumor regression, eradicate minimal residual illness, and prevent non-specific or unpleasant effects. These vaccines can assist in the elimination of cancer cells from various organs or organ systems in the body, with minimal risk of tumor recurrence or metastasis. Vaccines and antigens for anticancer therapy are discussed in this review, including current vaccine adjuvants and mechanisms of action for various types of vaccines, such as DNA- or mRNA-based cancer vaccines. Potential applications of these vaccines focusing on their clinical use for better therapeutic efficacy are also discussed along with the latest research available in this field.

Permeation enhancer nanovesicles mediated topical delivery of curcumin for the treatment of hyperpigmentation.

The main aim of the present study was to develop curcumin (CUR) loaded permeation enhancer-lipid vesicles for the treatment of hyperpigmentation. Hyperpigmentation is an acquired skin disorder characterized by uneven skin coloration, mainly in the regions of the facial skin, affecting millions of people worldwide. It often occurs in visible areas, hence causing significant negative psychological and social impacts. In the present study, curcumin-loaded permeation enhancer nanovesicles (PE-NVs) were developed by modified ethanol injection method and dimethyl sulfoxide was added as a penetration enhancer. PE-NVs were subjected to various physicochemical characterizations and drug permeation studies across the skin. The PE-NVs were tested for their efficacy in a sunlight-induced hyperpigmented rabbit skin model. Topical application of PE-NVs reduced symptoms of hyperpigmentation as compared with CUR methanolic solution because of higher accumulation because of better permeation into skin layers. Histopathological studies also confirmed the effectiveness of PE-NVs, since they reduced hyperpigmentation-induced lesions. Results confirmed that PE-NVs is a potential drug delivery system for topical administration drugs to treat skin-associated inflammatory disorders.

Phospholipid-polymer hybrid nanoparticle-mediated transfollicular delivery of quercetin: prospective implement for the treatment of androgenic alopecia.

Objectives: The aim of the study was to deliver effective doses of quercetin (Que) to the lower region of hair follicles (HFs) using the transfollicular route through dipalmotylphosphatidylcholine (DPPC)-reinforced poly lactide-co- glycolide nanoparticles (DPPC-PLGA hybrid NPs) for the treatment of alopecia. Method: PLGA and DPPC-PLGA hybrid NPs were prepared by double-emulsification solvent evaporation method. NPs were characterized for size, shape, zeta potential entrapment and drug release. Drug-polymer interactions were determined by infrared spectroscopy (Fourier transform infrared spectroscopy, FTIR) and differential scanning calorimetry (DSC). Follicular uptake of fluorescent marker tagged NPs was assessed on isolated rat skin by fluorescent microscopy. Potential of hybrid NPs to induce hair regrowth was tested on testosterone-induced alopecia in rat models by visual inspection, hair follicular density measurement (no./mm), and histological skin tissue section studies. Key findings: Hybrid NPs had mean vesicles size 339 ± 1.6, zeta potential -32.6 ± 0.51, and entrapment efficiency 78 ± 5.5. Cumulative drug release after 12 h was found to be 47.27 ± 0.79%. FTIR and DSC confirmed that drug was independently dispersed in the amorphous form in the polymer. Data from fluorescence microscopy suggested that NPs were actively taken up by HFs. In-vivo studies on alopecia-induced rat models showed that hybrid NPs improved hair regrowth potential of Que and accumulation of NPs at HFs end region inhibit HFs cells apoptosis. Conclusion: This study concludes that phospholipid-polymer hybrid NPs could be the promising transfollicular delivery system for Que in the treatment of androgenic alopecia management.

Novel Biomimetic Reconstituted Built-in Adjuvanted Hepatitis B Vaccine for Transcutaneous Immunization.

Transcutaneous immunization is the administration of a vaccine on the skin to generate efficient systemic and mucosal immune responses against an antigen. In the present study, reconstituted hepatitis B surface antigen vesicles (HBsAg-REVs) integrated with monophosphoryl lipid A were prepared by the delipidation-reconstitution method and tested as built-in adjuvanted vaccine, system for transcutaneous immunization using a combined approach of tape strippings, and enhanced antigen skin contact time. Prepared vesicles were extensively characterized for size, shape, zeta potential, and antigen protein loading efficiency. Following topical application, HBsAg-REVs skin permeation on isolated rat skin and cell uptake by bone marrow-derived dendritic cells were determined by confocal laser scanning microscopy and flow cytometry, respectively. The humoral and cellular immune responses elicited by HBsAg-REVs via transcutaneous immunization were comparable to the marketed intramuscular hepatitis B vaccine formulation with predefined immunization protocols. This study supports that delivery of reconstituted HBsAg vesicles via transcutaneous route may open a new vista for designing topical vaccines with possible immune protection against hepatitis B in future.

Chylomicron mimicking solid lipid nanoemulsions encapsulated enteric minicapsules targeted to colon for immunization against hepatitis B.

The oral route is one of the most convenient routes for drug and/or vaccine delivery. Yet variable nature of gastrointestinal tract due to transient changes in pH, physiology, and flora throughout the gut together with hostile nature of peptide drugs/vaccines when given by this route results in limited success. Colon targeting is a recent area of interest for most of the research among which hard gelatin coated capsules is one such important and useful contrivance. The present study assesses the mucosal immunization with HBsAg loaded lyophilized nanoparticles delivered in the colonic region using enteric coated minicapsules. Designed minicapsules offers better compliance and oral vaccine antigen delivery to the colonic region which involving mucosal exposure thus mimicking the natural pathogen entry in the body. The present study is an extension of our reported work where nanoparticles were administered to the colon through the rectal route. Lyophilized nanoparticles were characterized for particle size, in-vitro release and antigen integrity along with cell uptake study. Particles had ~241 ±â€¯32 nm sizes, flattened yet spherical in morphology. Enteric coated minicapsules were evaluated for size, coating thickness, and dissolution profile. In-vivo immune response assured its immunogenic potential with profound IgG (485 ±â€¯41 mIU/ml) and IgA (885 ±â€¯126 mIU/ml) antibody production as compared to marketed recombinant hepatitis B antigen formulation (Gene Vac-B®) which induce IgG and IgA titer; 1027 ±â€¯62 mIU/ml and 220 ±â€¯11 mIU/ml respectively following well established immunization protocol. Former induced significant mucosal immunity due to the involvement of Common Mucosal Immune System (CMIS). The study supports the workable novel approach for immune protection against hepatitis B.

Combined adjuvant-delivery system for new generation vaccine antigens: alliance has its own advantage.

Vaccines are a significant historical accomplishment in medical science due to its significance in saving millions of lives around the world with a manifold decline in disease burden and health expenditure. Since last decade, extensive efforts in vaccine design based on rational and experimental set up prompts the acknowledgement of several protective antigens; however, the utilization of those antigens as intense safe vaccines is still far beyond their discovery. The advancement of accomplished vaccines will need the combination of numerous strategies. In this way, the vaccine can be capable of provoking an abundant and effective immunization to compete against antigens with minimal/no adverse effects on recipients. First, stable and striking enough on the pharmaceutical point of view. Second, application of rational and realistic approaches to select an appropriate combination of adjuvant, antigen and delivery vehicle in the suitable formulation. Different vaccine adjuvants-delivery system combinations were discussed here elaborately, which are approved/licensed for human vaccines and are in various phases of clinical trials and pre-clinical trials. Challenges/limitations associated with vaccine designing and parameters to be considered, approaches to be applied, using available adjuvants are also detailed.

Protease loaded permeation enhancer liposomes for treatment of skin fibrosis arisen from second degree burn.

Cysteine protease (papain) is a plant derived enzyme and due to its collagenolytic activity has potential in fibrosis reduction. However, a major hurdle in its use as fibrosis reducing agent is to overcome stratum corneum skin barrier via topical application, owing to its hydrophilic and high molecular weight and protein nature which is prone to degradation. The aim of the present study was to develop a penetration enhancer incorporated drug delivery system, i.e. propylene glycol (PG) liposomes, loaded with papain for application in fibrosis therapy. Papain loaded PG-liposomes were prepared by the solvent injection method and characterized by size, shape, zeta potential, entrapment efficiency, drug release and stability. Papain conformational changes due to process stress were evaluated by electrophoresis and fluorescence spectroscopy. Biological evaluation was carried out in rodents by skin irritation and percent fibrosis reduction assays following induction of fibrosis arisen due to controlled second degree burn. Papain loaded PG-liposomes had mean vesicle size 180±30.3, zeta potential -25±1, polydispersity index 0.181 and 85±4.3% entrapment efficiency. Cumulative drug release after 8h was found to be 74.26±3.0%. SDS-PAGE and fluorescence spectroscopic studies confirmed the stability of papain after incorporation in PG-liposomes. Fibrosis reduction studies in animal models revealed that PG-liposomes incorporated papain improved fibrosis reduction significantly in comparison to conventional liposomes and free papain solution (p <0.05). Data suggest that propylene glycol incorporated liposomal system enhances papain proteolytic and collagenolytic activity along with a reduction in skin irritancy via preventing direct contact of papain with skin, improves papain therapeutic fibrosis reduction potential, an approach that may provide an efficient alternative for protease mediated fibrosis reduction in a variety of demanding circumstances.

Nanoparticulate mediated transcutaneous immunization: Myth or reality.

Transcutaneous immunization (TCI) is a promising route of vaccine delivery through skin due to many well documented advantages. The main obstacle in TCI is the skin's top dead layer i.e. stratum corneum which is difficult to penetrate. Efficiently delivery of antigen to the immune competent cells of epidermis or dermis in TCI might elicit an effective immune response. In this review, skin immunology with a particular focus on potential of immunological active receptors in influencing adaptive immune responses is highlighted. The challenges with TCI and methods to improve it using different adjuvants, chemical and physical approaches, delivery systems, and combination of above methods to further improve immune response following skin application of antigen are elaborately discussed. Nanoparticulate vaccine delivery systems with reference to their applications in TCI are classified according to their chronological development. Conclusively, clinical translations of above methods are also briefly reviewed. FROM THE CLINICAL EDITOR: Transcutaneous immunization has been investigated by many as a promising route of vaccination. In this comprehensive review article, the authors described and discussed the existing knowledge and difficulties in this approach. Furthermore, ways of improving transcutaneous delivery were also reviewed.

Proteins and peptides: The need to improve them as promising therapeutics for ulcerative colitis.

The present review briefly describes the nature, type and pathogenesis of ulcerative colitis, and explores the potential use of peptides and proteins in the treatment of inflammatory bowel disease, especially ulcerative colitis. Intestinal absorption and the barrier mechanism of peptide and protein drugs are also discussed, with special emphasis on various strategies which make these drugs better therapeutics having high specificity, potency and molecular targeting ability. However, the limitation of such therapeutics are oral administration, poor pharmacokinetic profile and decreased bioavailability. The recent findings illustrated in this review will be helpful in designing the peptide/protein drugs as a promising treatment of choice for ulcerative colitis.

Development and validation of TLC-densitometric method for determination of lipid A adjuvant as a bulk and in solid fat nanoemulsions.

A simple, sensitive, selective and precise high-performance thin-layer chromatographic method was developed for determination of lipid A (MPLA) adjuvant as a bulk and in solid fat nanoemulsions. Chromatographic separations were performed on thin-layer chromatography aluminum plates precoated with silica gel 60 F-254 as stationary phase and chloroform-methanol-ethyl acetate solution (10:2:4, v/v/v) as mobile phase. With this solvent system, compact spots for MPLA at Rf value 0.80 ± 0.02 were obtained. Densitometric analysis of MPLA was carried out in absorbance mode at 357 nm. Linear regression analysis for the calibration plots showed good linear relationship with r = 0.9996 in the concentration range of 20-100 ng/spot. The mean values (±SD) of slope and intercept were found to be 7.355 ± 0.006 and 109.52 ± 0.170, respectively. Limits of detection (LOD) and quantitation (LOQ) were observed at 3.096 and 9.382 ng/spot, respectively.The method was validated for precision, accuracy, robustness and recovery as per the International Conference on Harmonization guidelines. Statistical analysis proved that the developed method for quantification of MPLA as a bulk and in solid fat nanoemulsions is reproducible, selective and economical. This method could be applied for quantitative assay of MPLA in lipid-based vaccine formulations.