This study aimed to investigate the in vitro skin permeation and in vivo antineoplastic effect of curcumin by using liposomes as the transdermal drug-delivery system. Soybean phospholipids (SPC), egg yolk phospholipids (EPC), and hydrogenated soybean phospholipids (HSPC) were selected for the preparation of different kinds of phospholipids composed of curcumin-loaded liposomes: C-SPC-L (curcumin-loaded SPC liposomes), C-EPC-L (curcumin-loaded EPC liposomes), and C-HSPC-L (curcumin-loaded HSPC liposomes). The physical properties of different lipsomes were investigated as follows: photon correlation spectroscopy revealed that the average particle sizes of the three types of curcumin-loaded liposomes were 82.37 ± 2.19 nm (C-SPC-L), 83.13 ± 4.89 nm (C-EPC-L), and 92.42 ± 4.56 nm (C-HSPC-L), respectively. The encapsulation efficiency values were found to be 82.32 ± 3.91%, 81.59 ± 2.38%, and 80.77 ± 4.12%, respectively. An in vitro skin penetration study indicated that C-SPC-L most significantly promoted drug permeation and deposition followed by C-EPC-L, C-HSPC-L, and curcumin solution. Moreover, C-SPC-L displayed the greatest ability of all loaded liposomes to inhibit the growth of B16BL6 melanoma cells. Therefore, the C-SPC-L were chosen for further pharmacodynamic evaluation. A significant effect on antimelanoma activity was observed with C-SPC-L, as compared to treatment with curcumin solution in vivo. These results suggest that C-SPC-L would be a promising transdermal carrier for curcumin in cancer treatment.

https://www.mdpi.com/1420-3049/17/5/5972/pdf?origin=publication_detail

Preparation of curcumin-loaded liposomes and evaluation of their skin permeation and pharmacodynamics.

The first study on application of Design of Experiments (DoE) in optimizing drug formulation appeared in 1967. Since then the number of literature reports on the use of DoE optimization in development of drug delivery technologies has been piling up steadily. Such systematic techniques find their use in every type of conventional dosage form and modern drug delivery system. The drug delivery devices investigated for optimization using response surface methodology include controlled release compressed matrices, microparticulates, macroparticulates, vesicular systems, floating systems, bioadhesive systems, semisolids, transdermals, and inhalations. The optimized processes mainly include extrusion-spheronization, pelletization, microencapsulation, coating, granulation, and tableting. Part I of this article [Crit Rev Ther Drug Carrier Syst 2005; 22(1):27-106] dealt with the salient steps involved in the DoE optimization methodology using diverse experimental designs. Part II deals with various retrospective literature findings as well as the prospective application of such DoE procedures while optimizing varied drug delivery technologies. A vast account of various DoE reports on optimization of diverse drug delivery system and processes along with the critical graphical analysis of various designs, input, and response variables have been presented here in a categorical form. Such an explicit and updated review on drug delivery optimization has not been published anywhere else in the recent past.

Optimizing drug delivery systems using systematic "design of experiments." Part II: retrospect and prospects.

Lecithin-based nanostructured gels for skin delivery: an update on state of art and recent applications.

Ex vivo skin delivery of diclofenac by transcutol containing liposomes and suggested mechanism of vesicle-skin interaction.

Highly chemoselective intramolecular amination of propargylic C(sp(3))-H bonds has been demonstrated for N-bishomopropargylic sulfamoyl azides through cobalt(II)-based metalloradical catalysis. Supported by D(2h)-symmetric amidoporphyrin ligand 3,5-Di(t)Bu-IbuPhyrin, the cobalt(II)-catalyzed C-H amination proceeds effectively under neutral and nonoxidative conditions without the need of any additives, and generates N2 as the only byproduct. The metalloradical amination is suitable for both secondary and tertiary propargylic C-H substrates with an unusually high degree of functional-group tolerance, thus providing a direct method for high-yielding synthesis of functionalized propargylamine derivatives.

Chemoselective Amination of Propargylic C(sp3)H Bonds by Cobalt(II)‐Based Metalloradical Catalysis

The optimization of the method of preparation of idoxuridine (IDU) liposomes by the reverse phase evaporation (REV) method was carried out by three variables at three levels (3(3)) factorial design. The three independent variables selected were volume of organic phase (x1), volume of aqueous phase (x2), and drug/phosphatidylcholine/cholesterol in molar ratio (x3). Twenty-seven batches of IDU liposomes were prepared by the REV method and subjected to evaluation for percentage drug entrapment (PDE), size, and size distribution. A reduced polynomial equation was derived by multiple regression of the data of PDE and the transformed values of the three independent variables. Three contour plots at fixed level of-- 1 (low), 0 (medium), and 1 (high) of major contributing variable (x3) were plotted between x1 and x2 at predetermined PDE to understand the physical meaning of independent variables. Liposomal gels were prepared by dispersing optimized IDU liposomes in 2%w/w and 5%w/w (HPMC) K4M gel bases so as to contain 1%w/w IDU (LIG-1 and LIG-2, respectively). The percentage of drug retention (PDR) studies of optimized batch 14 (Lipo-14) and LIG-1 and LIG-2 were carried out at three different storage conditions (2-8 degrees C, 25 +/- 2 degrees C, and 37 degrees C). A comparative diffusion study of LIG-1 and LIG-2 with PIG-1 and PIG-2 (1%w/w IDU with components of liposome dispersed in 2%w/w and 5%w/w HPMC K4M gel bases, respectively), respectively, through human cadaver skin was conducted. A comparative double blind clinical pilot study of optimized LIG-2 gel was carried out for eight weeks and compared with PIG-2 on 20 Herpes simplex patients (10 patients each for HSV-1 and HSV-2, divided into two groups each of 5 patients). Batch 14 (Lipo-14) was found to have maximum PDE of 74.4%. The PDR study showed maximum drug retention at 2-8 degrees C. A significant increase in PDR (p<0.05) was observed in LIG-1 and LIG-2 when compared with Lipo-14 at all the three temperatures. In the diffusion studies, a significant (p<0.05) flux reduction; 3.5 times in LIG-1 when compared with PIG-1 and 2.3 times in LIG-2 when compared with PIG-2 was observed. Approximately 2.2- and 2.5-fold increase in skin drug retention in LIG-1 and LIG-2, respectively, was determined. A double blind clinical study demonstrated an approximately 2.0- and 1.6-fold increase in average percentage improvement in healing of the lesions in patients suffering from HSV-1 and HSV-2 diseases, respectively, when treated with LIG-2 compared with PIG-2. However, complete removal of lesions was not observed. Local side effects such as itching, burning, inflammation in HSV-1 and HSV-2, and burning micturation in HSV-2 associated with the use of PIG-2 were reduced considerably with the use of LIG-2. The findings of this investigation establish the role of the derived equation and plotted contour plots in predicting the values of independent variables for preparation of IDU liposomes by the REV method. The study also demonstrated that IDU liposomal gels retain more drug when compared with plain liposomes at all temperatures for the period of three months, while maximum PDR was found at refrigeration temperature. The skin retention of IDU was enhanced due to its entrapment in the liposomal vesicles. The clinical study suggested the improvement of therapeutic efficacy of IDU entrapped in liposomes in treatment of HSV-1 and HSV-2 patients.

Topical liposomal gel of idoxuridine for the treatment of herpes simplex: pharmaceutical and clinical implications.

Background: Dermatologic conditions have different presentation and management in pediatric age group from that in adult; this to be studied separately for statistical and population based analysis. Objective: To study the pattern of various dermatoses in infants and children in tertiary health care center in South Gujarat region. Materials and Methods: This is a prospective study; various dermatoses were studied in pediatric patients up to 14 years of age attending the Dermatology OPD of New Civil Hospital, Surat, Gujarat over a period of 12 months from June 2009 to June 2010. All patients were divided into four different study groups: 1 to 6 years and 7 to 14 years. Results: There were 596 boys and 425 girls in total 1021 study populations. Majority of the skin conditions in neonates were erythema toxicum neonatorum (12.97%), scabies (9.92%), mongolian spot (9.16%), and seborrheic dermatitis (7.63%). In > 1 month to 14 years age group of children among infectious disorder, children were found to be affected most by scabies (24.49%), impetigo (5.96%), pyoderma (5.62%), molluscum contagiosum (5.39%), tinea capitis (4.49%), leprosy (2.02%), and viral warts (1.35%) while among non-infectious disorders, they were affected by atopic dermatitis (4.27%), pityriasis alba (4.16%), seborrheic dermatitis (3.60%), pityriasis rosea (3.15%), others (3.01%), phrynoderma (2.70%), lichen planus (2.58%), contact dermatitis (1.57%) and ichthyosis (1.45%). Conclusion: There is a need to emphasize on training the management of common pediatric dermatoses to dermatologists, general practitioners and pediatricians for early treatment.

A Clinico-Etiological Study of Dermatoses in Pediatric Age Group in Tertiary Health Care Center in South Gujarat Region.

We describe two fatal cases of low dose methotrexate (MTX) toxicity in patients with psoriasis, emphasizing the factors that exacerbate MTX toxicity. The first patient was a 50-year-old male of psoriasis on intermittent treatment with MTX. After a treatment-free period of six months, he had self-medication of MTX along with analgesic for joint pain for one week which followed ulceration of the lesions, bone marrow suppression, and eventually death. The second patient was a 37-year-old male of psoriasis, who has taken MTX one week earlier without prior investigations. He had painful ulcerated skin lesions and bone marrow suppression. On investigations, he showed high creatinine level and atrophied, nonfunctioning right kidney on ultrasonography. In spite of dialysis, he succumbed to death. MTX is safe and effective if monitored properly, but inadvertent use may lead to even death also. Prior workup and proper counseling regarding the drug interactions as well as self-medication should be enforced.

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Acute methotrexate toxicity: a fatal condition in two cases of psoriasis.

BACKGROUND Acyclovir (ACY) is effective in the treatment of herpes simplex (HSV-1) & (HSV-2) but has systemic toxic effects if given orally or intravenously. ACY has not been used to treat the disease topically due to poor drug penetration into skin. A novel 1% liposomal ACY topical gel in a 5% Hydroxypropylmethyl cellulose (HPMC) K4M gel base has been developed and clinically evaluated in HSV-1 and HSV-2 patients. MATERIAL/METHODS 26 patients suffering from recurrent mild facial (HSV-1) and genital (HSV-2) infections (HSV-1: 4F, 6M, age 21-34 years; HSV-2: 16M, age 24-40 years) were subjected to double blind clinical evaluation. Plain ACY gel (PAG) and Liposomal ACY gel (LAG) were clinically evaluated by application five times daily on herpetic lesions for up to eight weeks. RESULTS A significant increase in the average percent improvement of lesion healing was observed in HSV-1 and HSV-2 patients after 2-3 weeks treatment with LAG, as well as a significant decrease in side effects associate with ACY, such as itching and burning in both HSV-1 and HSV-2, and burning micturation in HSV-2. CONCLUSIONS The results demonstrate that a five-fold reduction in the ACY content in liposomal gel is sufficient for the complete healing of herpetic lesions in HSV-1 and HSV-2 infection. The increased duration of topical therapy may be acceptable for patients suffering from mild herpetic lesions because of the advantage of avoiding systemic and local side effects

Role of acyclovir gel in herpes simplex: clinical implications.

Background: Outbreak of syphilis, i.e., 16 cases of rapid plasma reagin (RPR) reactive cases of syphilis was reported in Community Based Organization (CBO) Sahyog of Surat, India, from April to August 2014. The aim of the study was to find risk factors and take immediate actions to prevent spread. Materials and Methods: Outbreak investigation of 16 Female Sex Workers of CBO Sahyog in Surat who were found Rapid Plasma Reagin (RPR) and Treponema Pallidum Hemagglutination Assay (TPHA) positive from April to August 2014; was carried out. Clinico-epidemiological and laboratory-based evidence for different sexually transmitted infections (STIs) conducted at Government Medical College, New Civil Hospital, Surat. Root cause analysis (RCA) of index case was carried out. Results: Desk review for the past 3 years data of STI revealed total STI cases as 88 (2011), 95 (2012), and 130 (2013), of which 4, 2, and 2 found RPR reactive, respectively. Data from April to August 2014 revealed 16 RPR reactive cases and confirmed by TPHA. On examination, one had ulcerative cervical lesion, rest did not have any symptoms of syphilis. Eleven had vaginal/cervical discharge, 11 had lower abdominal pain. A total of 11 had unprotected sex, 7 encountered condom tear in the past 6 months, and 5 reported sexual violence. Seven had sexual activity under influence of alcohol. Laboratory investigation revealed two as HIV-positive. RPR reactivity reported highest (9 out of 16) from same area of hotspot. RCA of probable index case revealed factors responsible as violence and nonuse of condoms. Conclusions: Outbreak investigation revealed one probable index case. All 16 treated with injection Penidure. Violence or condom tear is responsible for the spread. Crisis management team should be strengthened.

Dipak Umrigar

Papers

Topical liposomal gel of idoxuridine for the treatment of herpes simplex: pharmaceutical and clinical implications.

A Clinico-Etiological Study of Dermatoses in Pediatric Age Group in Tertiary Health Care Center in South Gujarat Region.

Acute methotrexate toxicity: a fatal condition in two cases of psoriasis.

Role of acyclovir gel in herpes simplex: clinical implications.

Rapid Response to Syphilis Outbreak among Female Sex Workers.